bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Gain in Wurtzite ZnO/ZnMgO Quantum Well Lasers
Authors: Park Seoung-Hwan , Kim Kwang Joo , Yi Sam Nyung , Ahn Doyeol , Lee Seung Joo
Published: December 2005

The optical gain of wurtzite ZnO/ZnMgO quantum well (QW) lasers is investigated using the non-Markovian gain model with many-body effects. The results are compared with those of GaN/AlGaN QW lasers. The ZnO/ZnMgO QW lasers are found to have a much larger optical gain than the GaN/AlGaN QW lasers for a given sheet carrier density. This is mainly attributed to the fact that the average hole effective mass and the transition matrix element of ZnO/ZnMgO QW lasers are smaller and larger than those of GaN/AlGaN QW lasers, respectively. Also, the radiative current density contribution to the threshold current density of ZnO/ZnMgO QW lasers is expected to be markedly reduced compared with that of the GaN/AlGaN QW lasers if a large threshold carrier density (> 3×1019 cm-3) is required for both systems. These results show that ZnO-based QW lasers are promising candidates for optoelectric applications in visible and UV regions.
Precipitation of Amorphous Ferromagnetic Semiconductor Phase in Epitaxially Grown Mn-Doped Ge Thin Films
Authors: Sugahara Satoshi , Lee Kok Leong , Yada Shinsuke , Tanaka Masaaki
Published: December 2005

We investigated the origin of ferromagnetism in epitaxially grown Mn-doped Ge thin films. Using low-temperature molecular beam epitaxy, Mn-doped Ge films were successfully grown without precipitation of ferromagnetic Ge–Mn intermetallic compounds, such as Mn5Ge3. Magnetic circular dichroism measurements revealed that the epitaxially grown Mn-doped Ge films exhibited clear ferromagnetic behavior, but the Zeeman splitting observed at the critical points was not induced by the s,p–d exchange interactions. High-resolution transmission electron microscopy and energy dispersive X-ray spectroscopy analyses show phase separation of amorphous Ge1-x
Mn
x
clusters with high Mn content from a Mn-free monocrystalline Ge matrix. Since amorphous Ge1-x
Mn
x
was characterized as a homogeneous ferromagnetic semiconductor, the precipitation of the amorphous Ge1-x
Mn
x
clusters is the origin of the ferromagnetic semiconductor behavior of the epitaxially grown Mn-doped Ge films.
Highly Stable a-Si:H Films Deposited by Using Multi-Hollow Plasma Chemical Vapor Deposition
Authors: Koga Kazunori , Inoue Toshihisa , Bando Kouki , Iwashita Shinya , Shiratani Masaharu , Watanabe Yukio
Published: December 2005

Hydrogenated amorphous silicon (a-Si:H) films of high stability against light exposure have been deposited by using a newly developed multi-hollow plasma chemical vapor deposition (CVD) method. Films deposited in the upstream region in the multi-hollow plasma CVD reactor are a-Si:H films without incorporating a-Si:H nano-particles (clusters), while those in the downstream region are a-Si:H films with incorporating clusters. A-Si:H films without clusters have a low initial defect density of 5 ×1015 cm-3 and keep the value even after 100 h exposure of intense light intensity of 240 mW/cm2, whereas a-Si:H films with clusters show a significant increase in defect density from its initial value of 5 ×1015 cm-3 to 2 ×1016 cm-3 after 100 h light exposure. These results indicate that suppression of clusters incorporated into films is the key to realizing highly stable a-Si:H films.
Growth of HfSiOx films by Vapor–Liquid Hybrid Deposition Utilizing Si(OC2H5)4/Hf(tOC4H9)4 Multilayer Adsorption
Authors: Hojo Daisuke , Xuan Yi , Yasuda Tetsuji
Published: December 2005

In this study, a HfSiO
x
deposition technique is described that takes advantage of the multilayer adsorption of Si(OC2H5)4 (TEOS) and Hf(
t
OC4H9)4 (HTB), followed by the hydrolysis of all of the layers in liquid water. A thickness distribution better than ±3% and a uniform Si:Hf ratio over the 4-in. wafer were achieved using this deposition technique. The n-type metal–insulator–semiconductor field-effect transistor (MISFET) incorporating the HfSiO
x
film exhibited well-behaved capacitance–voltage characteristics. The channel mobility of 81% compared well to the universal curve at an effective field of 0.8 MV cm-1.
Mutual Injection Locking between Sub-THz Oscillating Resonant Tunneling Diodes
Authors: Suzuki Safumi , Orihashi Naoyuki , Asada Masahiro
Published: December 2005

Mutual injection locking was observed for sub-THz oscillators consisting of GaInAs/AlAs resonant tunneling diodes integrated with slot antennas. In the simultaneous operation of two oscillators with the individual frequencies of 340 and 324 GHz on the same wafer, oscillation at a single line of 330 GHz was obtained. The obtained result is qualitatively discussed using the van der Pole equations.
Dependence of Tunnel Magnetoresistance in MgO Based Magnetic Tunnel Junctions on Ar Pressure during MgO Sputtering
Authors: Ikeda Shoji , Hayakawa Jun , Lee Young Min , Sasaki Ryutaro , Meguro Toshiyasu , Matsukura Fumihiro , Ohno Hideo
Published: December 2005

We investigated dependence of tunnel magnetoresistance effect in CoFeB/MgO/CoFeB magnetic tunnel junctions on Ar pressure during MgO-barrier sputtering. Sputter deposition of MgO-barrier at high Ar pressure of 10 mTorr resulted in smooth surface and highly (001) oriented MgO. Using this MgO as a tunnel barrier, tunnel magnetoresistance (TMR) ratio as high as 355% at room temperature (578% at 5 K) was realized after annealing at 325°C or higher, which appears to be related to a highly (001) oriented CoFeB texture promoted by the smooth and highly oriented MgO. Electron-beam lithography defined deep-submicron MTJs having a low-resistivity Au underlayer with the high-pressure deposited MgO showed high TMR ratio at low resistance-area product (RA) below 10 Ω µm2 as 27% at RA = 0.8 Ω µm2, 77% at RA = 1.1 Ω µm2, 130% at RA = 1.7 Ω µm2, and 165% at RA = 2.9 Ω µm2.
Three-Dimensional Waveguide Interconnection in Planar Lightwave Circuits by Direct Writing with Femtosecond Laser
Authors: Nasu Yusuke , Kohtoku Masaki , Hibino Yoshinori , Inoue Yasuyuki
Published: December 2005

The three-dimensional (3D) interconnection of waveguides in planar lightwave circuits (PLCs) is demonstrated. A femtosecond laser successfully interconnects the waveguides of PLCs with low loss by writing 3D waveguides in the PLCs. A directly written waveguide with a length of about 2000 µm crossed over another waveguide without any interaction. The excess losses at 1550 nm were 2.7 and 2.8 dB for the transverse electric (TE) and transverse magnetic (TM) modes, respectively.
Improved Conductance Method for Determining Interface Trap Density of Metal–Oxide–Semiconductor Device with High Series Resistance
Authors: Yang Hyundoek , Son Yunik , Choi Sangmoo , Hwang Hyunsang
Published: December 2005

The existence of series resistance in metal–oxide–semiconductor (MOS) devices can result in both the degradation of capacitance at a high frequency and the decrease in conductance. Using a conventional conductance method that does not consider the series resistance, the interface trap density can be underestimated. We propose an improved conductance method based on an equivalent circuit model including the series resistance. Compared with the conventional method, this new method enables the accurate determination of interface trap density.
Formation of Graphitic-C3N4 and α-C3N4 Fine Particles by DC Arc Discharge in NH3 Gas
Authors: Okazaki Tsugio , Tosaka Kazuo
Published: December 2005

Graphitic-C3N4 (AAA stacking mode) and α-C3N4 fine particles were successfully formed by dc arc discharge in NH3 gas. Synthesized particles were studied by transmission electron microscopy. Graphitic-C3N4 particles were observed on the graphite or independently in a dispersed state on the collodion film, with an average diameter of 15 nm. α-C3N4 fine particles were observed in a coagulated form with an average diameter of 30 nm.
Uniaxial Alignment of Alq3 by Laser-Assisted Molecular Beam Epitaxy
Authors: Ichikawa Hisashi , Saiki Koichiro , Suzuki Tadamasa , Hasegawa Tetsuya , Shimada Toshihiro
Published: December 2005

The surface morphology of tris(8-hydroxyquinoline)aluminum(III) (Alq3) epitaxially grown on KCl(001) was drastically changed by a simultaneous blue laser irradiation during vacuum deposition. Needle-shaped microcrystals were aligned to the polarization direction of the laser, parallel to the KCl[010] axis. The origin of alignment was discussed in comparison with the growth of non-polar organic molecular films, in which anisotropic heating played an important role.
Graphitization of Tetrahedral Amorphous Carbon Films Induced by Core Electron Excitations
Authors: Liang Shijin , Harada Yoshihisa , Shin Shik , Kitajima Yoshinori , Mera Yutaka , Maeda Koji
Published: December 2005

We studied effects of soft X-ray illumination on tetrahedral amorphous carbon (ta-C) films by in situ measuring spectra of X-ray absorption and resonant Auger electron emission. Illumination with 285 ±3.5 eV photons, resonant mainly with the π* peak associated with graphitic structures and partly with the tentatively assigned σ* core exciton peak, induced a change in the surface-sensitive absorption and Auger spectra which is interpreted as an increase of graphitic phase, similar to but slightly different from the structural conversion from sp3 to sp2 bonding that is induced by 200 keV electron beam irradiation previously found by the authors.
Long-Period-Grating-Loaded Semiconductor Separate-Confinement Heterostructure Waveguide for Polarization-Independent Gain-Equalizing Device
Authors: Tabuchi Hiromasa , Abe Toshitaka , Terada Kenichi , Utaka Katsuyuki
Published: December 2005

We report the notch filtering characteristics of an InGaAsP/InP long-period-grating-loaded separate-confinement heterostructure waveguide for a polarization-independent gain-equalizing device. We discussed the structure design and confirmed the fundamental characteristics of the device experimentally.
Conductivity Decrease in Carbon Nanotubes Caused by Low-Acceleration-Voltage Electron Irradiation
Authors: Suzuki Satoru , Kobayashi Yoshihiro
Published: December 2005

Effects of low-acceleration-voltage (20 kV) electron irradiation damage in single-walled carbon nanotubes (SWNTs) were studied by in-situ electric measurements. The irradiation drastically decreased the conductivity for both metallic and semiconducting nanotubes due to the irradiation-induced damage. Intensive electron irradiation made the SWNTs almost insulating. This phenomenon could be utilized to fabricate nanotube-based electric networks.
BGaN Micro-Islands as Novel Buffers for GaN Hetero-Epitaxy
Authors: Akasaka Tetsuya , Makimoto Toshiki
Published: December 2005

B
x
Ga1-x
N (x∼0.02) micro-islands provide novel buffers for growing GaN films and AlGaN/GaN heterostructures on sapphire substrates. These films and heterostructures show low threading dislocation density (TDD), low residual carrier concentration, and high two-dimensional electron gas (2DEG) mobility: Non-doped GaN films had the TDD of 2×108 cm-2 and the residual electron concentration of 9.4×109 cm-3 at 433 K. AlGaN/GaN heterostructures exhibited 2DEG Hall mobility of 1720 and 13100 cm2 V-1 s-1 at 300 and 77 K, respectively. An almost constant sheet electron density (2.9–4.2×1012 cm-2) was obtained in the wide temperature range from 500 to 77 K, indicating the absence of parallel conduction in the GaN buffer layers.
Schizotypal Personality: Neurodevelopmental and Psychosocial Trajectories
Authors: Raine Adrian
Published: December 2005

Schizotypal personality research holds the promise of critically important insights into the etiology and ultimate prevention of schizophrenia. This article provides a critical overview of diagnostic, developmental, demographic, psychosocial, genetic, neurodevelopmental, psychophysiological, neurochemical, neurocognitive, brain imaging, and prevention-treatment issues pertaining to this personality disorder. It is argued that genetic and early environmental influences act in concert to alter brain structure/function throughout development, resulting in disturbances to basic cognitive and affective processes that give rise to three building blocks of schizotypy—cognitive-perceptual, interpersonal, and disorganized features. Two clinical subtypes are hypothesized: (a) neurodevelopmental schizotypy, which has its roots in genetic, prenatal, and early postnatal factors, is relatively stable, has genetic affinity to schizophrenia, and may benefit preferentially from pharmacological intervention, and (b) pseudoschizotypy, which is unrelated to schizophrenia, has its roots in psychosocial adversity, shows greater symptom fluctuations, and may be more responsive to psychosocial intervention.
FOXP3: Of Mice and Men
Authors: Ziegler Steven F.
Published: December 2005

The immune system has evolved mechanisms to recognize and eliminate threats, as well as to protect against self-destruction. Tolerance to self-antigens is generated through two fundamental mechanisms: (a) elimination of self-reactive cells in the thymus during selection and (b) generation of a variety of peripheral regulatory cells to control self-reactive cells that escape the thymus. It is becoming increasing apparent that a population of thymically derived CD4+regulatory T cells, exemplified by the expression of the IL-2Rα chain, is essential for the maintenance of peripheral tolerance. Recent work has shown that the forkhead family transcription factor Foxp3 is critically important for the development and function of the regulatory T cells. Lack of Foxp3 leads to development of fatal autoimmune lymphoproliferative disease; furthermore, ectopic Foxp3 expression can phenotypically convert effector T cells to regulatory T cells. This review focuses on Foxp3 expression and function and highlights differences between humans and mice regarding Foxp3 regulation.
STARK DECELERATION AND TRAPPING OF OH RADICALS
Authors: van de Meerakker Sebastiaan Y.T. , Vanhaecke Nicolas , Meijer Gerard
Published: December 2005

▪ Abstract  The motion of polar molecules can be controlled by time-varying inhomogeneous electric fields. In a Stark decelerator, this is exploited to accelerate, transport, or decelerate a fraction of a molecular beam. When combined with a trap, the decelerator provides a means to store the molecules for times up to seconds. Here, we review our efforts to produce cold molecules via this technique. In particular, we present a new generation Stark decelerator and electrostatic trap that selects a significant part of a molecular beam pulse that can be loaded into the trap. Deceleration and trapping experiments using a beam of OH radicals are discussed.
Modulation of connexin43 alters expression of osteoblastic differentiation markers
Authors: Li Zhongyong , Zhou Zhiyi , Saunders Marnie M. , Donahue Henry J.
Published: December 2005

Gap junctional channels between cells provide a pathway for exchange of regulatory ions and small molecules. We previously demonstrated that expression of connexins and cell-to-cell communication parallel osteoblastic differentiation and that nonspecific pharmacological inhibitors of gap junctional communication inhibit alkaline phosphatase activity. In this study, we stably transfected connexin (Cx)43 antisense cDNA into the immortalized human fetal osteoblastic cell line hFOB 1.19 (hFOB/Cx43−). hFOB/Cx43− cells express lower levels of Cx43 protein and mRNA and display a 50% decrease in gap junctional intercellular communication relative to control [hFOB/plasmid vector control (pvc)]. This suggests that other connexins, such as Cx45, which is expressed to a similar degree in hFOB/Cx43− cells and hFOB/pvc cells, contribute to cell-to-cell communication in hFOB 1.19 cells. We observed almost total inhibition of alkaline phosphatase activity in hFOB/Cx43− cells despite only a 50% decrease in cell-to-cell communication. This suggests the intriguing possibility that Cx43 expression per se, independent of cell-to-cell communication, influences alkaline phosphatase activity and perhaps bone cell differentiation. Quantitative real-time RT-PCR revealed that mRNA levels for osteocalcin and core binding factor α1 (Cbfa1) increased as a function of time in hFOB/pvc but were inhibited in hFOB/Cx43−. Osteopontin mRNA levels were increased in hFOB/Cx43− relative to hFOB/pvc and decreased as a function of time in both hFOB/Cx43− and hFOB/pvc. Transfection with Cx43 antisense did not affect expression of type I collagen in hFOB 1.19 cells. These results suggest that gap junctional intercellular communication and expression of Cx43 contribute to alkaline phosphatase activity, as well as osteocalcin, osteopontin, and Cbfa1 expression in osteoblastic cells.
Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis
Authors: Ohashi Shinya , Nishio Akiyoshi , Nakamura Hajime , Kido Masahiro , Ueno Satoru , Uza Norimitsu , Inoue Satoko , Kitamura Hiroshi , Kiriya Keiichi , Asada Masanori , Tamaki Hiroyuki , Matsuura Minoru , Kawasaki Kimio , Fukui Toshiro , Watanabe Norihiko , Nakase Hiroshi , Yodoi Junji , Okazaki Kazuichi , Chiba Tsutomu
Published: December 2005

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of κB-α, thereby suppressing proinflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.
Electrical Feedback in the Cone Pedicle: A Computational Analysis
Authors: Dmitriev Andrey V. , Mangel Stuart C.
Published: December 2005

One of the fundamental principles of neuroscience is that direct electrical interactions between neurons are not possible without specialized electrical contacts, gap junctions, because the transmembrane resistance of neurons is typically much higher than the resistance of the adjacent extracellular space. However it has been proposed that in the retina direct electrical interactions between cones and second-order neurons occur due to the specific morphology of the cone synaptic terminal. This electrical mechanism could potentially explain the phenomenon of “negative feedback” from horizontal cells to cones and the recent finding that the tips of horizontal cell dendrites contain hemichannels has rekindled interest in the idea. We quantitatively evaluated the possibility that hemichannels and/or glutamate channels mediate electrical feedback from horizontal cells to cones. The calculations show that it is unlikely that an electrical mechanism plays a significant functional role because 1) the necessity of preserving adequate cone-to-horizontal-cell synaptic transmission limits the extracellular space resistance and the horizontal-cell dendritic transmembrane resistances to values at which the effectiveness of electrical feedback is very low and its electrical effect on the cone presynaptic membrane is negligible, 2) electrical feedback is most effective in the dark and weaker during light adaptation, which contradicts the experimental data, and 3) electrical negative feedback is associated with much stronger electrical positive feedback from horizontal cells to cones, a phenomenon that has never been reported. Therefore it is likely that negative feedback from horizontal cells to cones is chemical in nature.
Chronic IL-1β Signaling Potentiates Voltage-Dependent Sodium Currents in Trigeminal Nociceptive Neurons
Authors: Liu Lieju , Yang T. M. , Liedtke Wolfgang , Simon S. A.
Published: December 2005

The proinflammatory cytokine interleukin-1β (IL-1β) mediates inflammation and hyperalgesia, although the underlying mechanisms remain elusive. To better understand such molecular and cellular mechanisms, we investigated how IL-1β modulates the total voltage-dependent sodium currents ( INa) and its tetrodotoxin-resistant (TTX-R) component in capsaicin-sensitive trigeminal nociceptive neurons, both after a brief (5-min) and after a chronic exposure (24-h) of 20 ng/ml IL-1β. A brief exposure led to a 28% specific (receptor-mediated) reduction of INa in these neurons, which were found to contain type I IL-1 receptors (IL-1RI+) on both their soma and nerve endings. In marked contrast, after a 24-h exposure, the total sodium current was specifically increased by 67%, without significantly affecting the TTX-R component. This potentiation of INa was suppressed in the presence of selective inhibitors of protein kinase C and G-protein–coupled signaling pathways, thereby suggesting that INa can be modulated through multiple pathways. In summary, the potentiation of INa through chronic IL-1β signaling in nociceptive sensory neurons may be a critical component of inflammatory-associated hyperalgesia.
Synaptic and Extrasynaptic NMDA Receptor NR2 Subunits in Cultured Hippocampal Neurons
Authors: Thomas Christopher G. , Miller Ashleigh J. , Westbrook Gary L.
Published: December 2005

Early in development, neurons only express NR1/NR2B-containing N-methyl-d-aspartate (NMDA) receptors. Later, NR2A subunits are upregulated during a period of rapid synapse formation. This pattern is often interpreted to indicate that NR2A-containing receptors are synaptic and that NR2B-containing receptors are extrasynaptic. We re-examined this issue using whole cell recordings in cultured hippocampal neurons. As expected, the inhibition of whole cell currents by the NR2B-specific antagonist, ifenprodil, progressively decreased from 69.5 ± 2.4% [6 days in vitro (DIV)] to 54.9 ± 2.6% (8 DIV), before reaching a plateau in the second week (42.5 ± 2%, 12–19 DIV). In NR2A−/− neurons, which express only NR1/NR2B-containing NMDA receptors, autaptic excitatory postsynaptic currents (EPSCs; ≥12 DIV) were more sensitive to ifenprodil and decayed more slowly than EPSCs in wild-type neurons. Thus NR2B-containing receptors were not excluded from synapses. We blocked synaptic NMDA receptors with MK-801 during evoked transmitter release, thus allowing us to isolate extrasynaptic receptors. Ifenprodil inhibition of this extrasynaptic population was highly variable in different neurons. Furthermore, extrasynaptic receptors in autaptic cultures were only partially blocked by ifenprodil, indicating that NR2A-containing receptors are not exclusively confined to the synapse. Extrasynaptic NR2A-containing receptors were also detected in NR2A−/− neurons transfected with full-length NR2A. Truncation of the NR2A C terminus did not eliminate synaptic expression of NR2A-containing receptors. Our results indicate that NR2A- and NR2B-containing receptors can be located in either synaptic or extrasynaptic compartments.
Prehension Stability: Experiments With Expanding and Contracting Handle
Authors: Zatsiorsky Vladimir M. , Gao Fan , Latash Mark L.
Published: December 2005

We studied adjustments in digit forces and moments during holding a vertically oriented handle under slow, externally imposed changes in the width of the grasp. Subjects ( n = 8) grasped a customized motorized handle with five digits and held it statically in the air. The handle width either increased (expanded) or decreased (contracted) at a rate of 1.0, 1.5, or 2.0 mm/s, while the subjects were asked to ignore the handle width changes, and their attention was distracted. External torques of 0.0, 0.25, and 0.5 Nm were applied to the handle in two directions. Forces and moments at the digit tips were measured with six-component sensors. The analysis was performed at the virtual finger (VF) and individual finger (IF) levels (VF is an imagined finger that produces the same wrench, i.e., the force and moment, as several fingers combined). In all the tasks, the normal VF and thumb forces increased with the handle expansion and decreased with the handle contraction. Similar behavior was seen for the thumb tangential force. In contrast, the VF tangential force decreased with the handle expansion and increased with the handle contraction. The changes in the tangential forces assisted the perturbations in the tasks requiring exertion of the supination moments and annulled the perturbation in the pronation effort tasks. In the former tasks, the equilibrium was maintained by the changes of the moments of normal forces, whereas in the latter tasks, the equilibrium was maintained by the changes of the moments of the tangential forces. Analysis at the IF level has shown that the resultant force and moment exerted on the object could arise from dissimilar adjustments of individual fingers to the same handle width change. The complex adjustments of digit forces to handle width change may be viewed as coming from two sources. First, there are local spring-like adjustments of individual digit forces and moments caused by both mechanical properties of the digits and the action of spinal reflexes. These stiffness-like reactions mainly assist in perturbing the rotational equilibrium of the object rather than in maintaining it. Second, there are tilt-preventing adjustments defined by the common task constraints that unite the digits into a task-specific synergy. The “virtual springs theory” developed in robotics literature is insufficient for describing the phenomena observed in human grasping.
Functional Changes in Genetically Dysmyelinated Spinal Cord Axons ofShivererMice: Role of Juxtaparanodal Kv1 Family K+Channels
Authors: Sinha Kusum , Karimi-Abdolrezaee Soheila , Velumian Alexander A. , Fehlings Michael G.
Published: December 2005

Axonal dysfunction after spinal cord injury (SCI) and other types of neurotrauma is associated with demyelination and exposure of juxtaparanodal K+channels. In this study, sucrose gap electrophysiology using selective and nonselective K+channel blockers, confocal immunohistochemistry, and Western blotting were used to study the role of Kv1.1 and Kv1.2 K+channel subunits in dysmyelination-induced spinal cord axonal dysfunction in s hiverer mice, which lack the gene encoding myelin basic protein (MBP) and exhibit incomplete myelin sheath formation on CNS axons. The s hiverer spinal cord axons exhibited smaller amplitude of compound action potentials (CAPs), reduced conduction velocity, reduced excitability, and greater degree of high-frequency conduction failure. The “fast” K+channel blocker 4-aminopyridine, the toxin DTX-I, which targets the Kv1.1 and Kv1.2, but not DTX- K, which has higher selectivity for Kv1.1, increased the amplitude and area of CAPs of shiverer mice spinal cord axons but had insignificant effects in wild-type mice. Confocal immunohistochemistry showed that, unlike wild-type mice, which have a precise juxtaparanodal localization of the Kv1.l and Kv1.2 K+channel subunits, shiverer mouse axons displayed a dispersed distribution of these subunits along the internodes. In contrast, the Kv1.l and Kv1.2 subunits, Na+channels remained highly localized to the nodal regions. Western blotting showed an increased expression of Kv 1.1 and 1.2 in the shiverer mouse spinal cord. These results provide evidence that the neurological deficits associated with myelin deficiency reflect the altered distribution and expression of the K+channel subunits Kv1.l and Kv1.2 along the internodes of spinal cord axons associated with the biophysical consequences caused by alterations in the myelin sheaths.
Interglomerular Center-Surround Inhibition Shapes Odorant-Evoked Input to the Mouse Olfactory Bulb In Vivo
Authors: Vučinić Dejan , Cohen Lawrence B. , Kosmidis Efstratios K.
Published: December 2005

Mouse olfactory receptor proteins have relatively broad odorant tuning profiles, so single odorants typically activate a substantial subset of glomeruli in the main olfactory bulb, resulting in stereotyped odorant- and concentration-dependent glomerular input maps. One of the functions of the olfactory bulb may be to reduce the extent of this rather widespread activation before transmitting the information to higher olfactory centers. Two circuits have been studied in vitro that could perform center-surround inhibition in the olfactory bulb, one circuit acting between glomeruli, the other through the classical reciprocal synapses between the lateral dendrites of mitral cells and the dendrites of granule cells. One unanswered question from these in vitro measurements was how these circuits would affect the response to odorants in vivo. We made measurements of the odorant-evoked increase in calcium concentration in the olfactory receptor neuron terminals in the anesthetized mouse to evaluate the role of presynaptic inhibition in reshaping the input to the olfactory bulb. We compared the glomerular responses in 2- to 4-wk-old mice before and after suppressing presynaptic inhibition onto the receptor neuron terminals with the GABAB antagonist, CGP46381 . We find that the input maps are modified by an apparent center-surround inhibition: strongly activated glomeruli appear to suppress the release from receptor neurons terminating in surrounding glomeruli. This form of lateral inhibition has the effect of increasing the contrast of the sensory input map.
Differential Receptor Activation by Cockroach Adipokinetic Hormones Produces Differential Effects on Ion Currents, Neuronal Activity, and Locomotion
Authors: Wicher Dieter , Agricola Hans-Jürgen , Söhler Sandra , Gundel Matthias , Heinemann Stefan H. , Wollweber Leo , Stengl Monika , Derst Christian
Published: December 2005

Adipokinetic hormone (AKH) peptides in insects serve the endocrine control of energy supply. They also produce, however, neuronal, vegetative, and motor effects, suggesting that AKHs orchestrate adaptive behavior by multiple actions. We have cloned, for Periplaneta americana, the AKH receptor to determine its localization and, based on current measurements in neurons and heterologous expression systems, the mechanisms of AKH actions. Apart from fat body, various neurons express the AKH receptor, among them abdominal dorsal unpaired median (DUM) neurons, which release the biogenic amine octopamine. They are part of the arousal system and are involved in the control of circulation and respiration. Both the two Periplaneta AKHs activate the Gspathway, and AKH I also potently activates Gq. AKH I and—with much less efficacy—AKH II accelerate spiking of DUM neurons through an increase of the pacemaking Ca2+current. Because the AKHs are released from the corpora cardiaca into the hemolymph, they must penetrate the blood-brain barrier for acting on neurons. That this happens was shown electrophysiologically by applying AKH I to an intact ganglion. Systemically injected AKH I stimulates locomotion potently in striking contrast to AKH II. This behavioral difference can be traced back conclusively to the different effectiveness of the AKHs on the level of G proteins. Our findings also show that AKHs act through the same basic mechanisms on neuronal and nonneuronal cells, and they support an integration of metabolic and neuronal effects in homoeostatic mechanisms.
Responses of a Looming-Sensitive Neuron to Compound and Paired Object Approaches
Authors: Guest Bruce B. , Gray John R.
Published: December 2005

The lobula giant movement detector (LGMD) and its target neuron, the descending contralateral movement detector (DCMD), constitute a motion-sensitive pathway in the locust visual system that responds preferentially to objects approaching on a collision course. LGMD receptive field properties, anisotropic distribution of local retinotopic inputs across the visual field, and localized habituation to repeated stimuli suggest that this pathway should be sensitive to approaches of individual objects within a complex visual scene. We presented locusts with compound looming objects while recording from the DCMD to test the effects of nonuniform edge expansion on looming responses. We also presented paired objects approaching from different regions of the visual field at nonoverlapping, closely timed and simultaneous approach intervals to study DCMD responses to multiple looming stimuli. We found that looming compound objects evoked characteristic responses in the DCMD and that the time of peak firing was consistent with predicted values based on a weighted ratio of the half size of each distinct object edge and the absolute approach velocity. We also found that the azimuthal position and interval of paired approaches affected DCMD firing properties and that DCMDs responded to individual objects approaching within 106 ms of each other. Moreover, comparisons between individual and paired approaches revealed that overlapping approaches are processed in a strongly sublinear manner. These findings are consistent with biophysical mechanisms that produce nonlinear integration of excitatory and feed-forward inhibitory inputs onto the LGMD that have been shown to underlie responses to looming stimuli.
Survivin Expression Is Regulated by Coexpression of Human Epidermal Growth Factor Receptor 2 and Epidermal Growth Factor Receptor via Phosphatidylinositol 3-Kinase/AKT Signaling Pathway in Breast Cancer Cells
Authors: Asanuma Hiroko , Torigoe Toshihiko , Kamiguchi Kenjiro , Hirohashi Yoshihiko , Ohmura Tousei , Hirata Koichi , Sato Masaaki , Sato Noriyuki
Published: December 2005

Survivin, a member of the inhibitor of apoptosis protein family, is widely expressed in a variety of human cancer tissues. Survivin inhibits activation of caspases, and its overexpression can lead to resistance to apoptotic stimuli. In this study, survivin protein expression was assessed by immunohistochemical staining of 195 invasive breast cancer specimens. Overall, 79.5% of the tumors were positive for survivin. The expression of epidermal growth factor receptor (EGFR) family, human epidermal growth factor receptor 2 (HER2) and EGFR, was also examined in 53 cases, and consequently, it was indicated that survivin positivity might be correlated with the coexpression of HER2 and EGFR. To clarify the regulatory mechanism of survivin expression in breast cancer cells, the effect of HER2 and/or EGFR expression on the survivin levels was examined. It was revealed that the survivin protein level was up-regulated by the coexpression of HER2 and EGFR, leading to the increased resistance against etoposide-induced apoptosis in breast cancer cells. Conversely, survivin levels and apoptosis resistance were decreased when cells were treated with HER2-specific inhibitor, Herceptin. Although Herceptin could down-regulate both phosphatidylinositol 3-kinase (PI3K)/AKT signal and mitogen-activated protein/extracellular signal-related kinase (ERK) kinase 1 (MEK1)/ERK signal in HER2-positive breast cancer cells, PI3K-specific inhibitor but not MEK1-specific inhibitor could decrease the survivin levels. The present study clarified the regulatory mechanism of HER2 in the expression of survivin protein in breast cancer cells.
CD24 Expression Causes the Acquisition of Multiple Cellular Properties Associated with Tumor Growth and Metastasis
Authors: Baumann Petra , Cremers Natascha , Kroese Frans , Orend Gertraud , Chiquet-Ehrismann Ruth , Uede Toshi , Yagita Hideo , Sleeman Jonathan P.
Published: December 2005

The glycosylphosphatidylinositol-anchored membrane protein CD24 functions as an adhesion molecule for P-selectin and L1 and plays a role in B-cell development and neurogenesis. Over the last few years, a large body of literature has also implicated CD24 expression in tumorigenesis and progression. Here, we show that ectopic CD24 expression can be sufficient to promote tumor metastasis in experimental animals. By developing a doxycycline-inducible system for the expression of CD24 in breast cancer cells, we have also analyzed the cellular properties that CD24 expression influences. We found that CD24 expression increased tumor cell proliferation. Furthermore, in addition to promoting binding to P-selectin, CD24 expression also indirectly stimulated cell adhesion to fibronectin, collagens I and IV, and laminin through the activation of α3β1 and α4β1 integrin activity. Moreover, CD24 expression supported rapid cell spreading and strongly induced cell motility and invasion. CD24-induced proliferation and motility were integrin independent. Together, these observations implicate CD24 in the regulation of multiple cell properties of direct relevance to tumor growth and metastasis.
Interleukin-6, Secreted by Human Ovarian Carcinoma Cells, Is a Potent Proangiogenic Cytokine
Authors: Nilsson Monique B. , Langley Robert R. , Fidler Isaiah J.
Published: December 2005

Angiogenesis, a key rate-limiting step in the growth and dissemination of malignant tumors, is regulated by the balance between positive and negative effectors. Recent studies indicate that the pleiotropic cytokine interleukin-6 (IL-6) may contribute to the vascularization of some tumors by disrupting the equilibrium between positive and negative angiogenic regulatory molecules. We determined whether IL-6 participates in the angiogenesis observed during the progression of ovarian carcinoma. We measured IL-6 production by human ovarian cancer cell lines in vitro and in vivo. Not all cell lines secreted IL-6 in vitro; however, when the cell lines were implanted into the peritoneal cavity of female nude mice, every line secreted IL-6. Most human ovarian carcinoma cell lines tested secreted significant levels of the soluble IL-6 receptor (sIL-6R). Endothelial cell lines established from the ovary and mesentery of female H-2Kb-tsA58 mice were tested for response to IL-6. Both endothelial cell lines expressed the IL-6R and their stimulation with the exogenous ligand significantly enhanced cell migration and activated the downstream signaling molecule signal transducers and activators of transcription 3. Dual immunohistochemical staining for IL-6R and CD31 revealed IL-6R expression on human endothelial cells within normal ovary and carcinoma specimens. Gelfoam sponges containing 0.4% agarose and IL-6 or basic fibroblast growth factor and implanted into the subcutis of BALB/c mice were vascularized to the same extent. Collectively, the data indicate that ovarian tumor cells secreted IL-6, a highly angiogenic cytokine that supports progression of disease.
Induction of Aromatase Expression in Cervical Carcinomas: Effects of Endogenous Estrogen on Cervical Cancer Cell Proliferation
Authors: Nair Hareesh B. , Luthra Roopa , Kirma Nameer , Liu Ya-Guang , Flowers Lisa , Evans Dean , Tekmal Rajeshwar Rao
Published: December 2005

Epidemiologic studies have implicated estrogenic exposure as well as human papilloma virus (HPV) infection in cervical carcinogenesis, and some studies have suggested that estrogen and HPV may play synergistic roles in cervical tumorigenesis. In this study, we report a novel finding that ∼35% of cervical carcinomas tested (n = 19) express aromatase, the enzyme responsible for converting androgen to estrogen, the rate-limiting and final step in estrogen biosynthesis. On the other hand, no aromatase expression was detected in precancerous (n = 42) or normal cervical (n = 17) tissue samples. Increased aromatase was associated with increases in estrogen receptors (ER-α and ER-β) and a decrease in progesterone receptor levels, suggesting that in situ estrogen signaling via ER may be involved in tumor growth. Stable overexpression of aromatase in HPV+ cervical cancer cells resulted in increased cellular proliferation, anchorage-independent growth, and ER expression and activity. In contrast, little change in ER was observed in HPV− cells. Steroid hormone receptor expression observed in vitro paralleled that seen in cervical carcinomas expressing aromatase. Aromatase overexpression also induced the expression of cyclin D1, proliferating cell nuclear antigen, and the HPV oncogenes, E6 and E7. Furthermore, the data underscores the importance of steroid receptor (estrogen and progesterone receptors) regulation in cervical carcinogenesis. To our knowledge, this is the first report demonstrating the induction of aromatase expression in cervical carcinomas, and opens the possibility that aromatase inhibitors may be potential therapeutic agents in cervical carcinomas expressing aromatase.
Cloning and Characterization of a p53 and DNA Damage Down-regulated Gene PIQ that Codes for a Novel Calmodulin-Binding IQ Motif Protein and Is Up-regulated in Gastrointestinal Cancers
Authors: Luo Xiuquan , He Qin , Huang Ying , Sheikh M. Saeed
Published: December 2005

We have identified a p53 and DNA damage–regulated gene that encodes a novel IQ motif protein, which we have named p53 and DNA damage–regulated IQ motif protein (PIQ). PIQ has two isoforms, long (PIQ-L) and short (PIQ-S), and both bind to calmodulin in the presence and absence of calcium. PIQ expression is down-regulated by p53 and DNA damage–inducing agents, whereas PIQ itself represses the expression of p53 up-regulated modulator of apoptosis that is a key mediator of p53-induced apoptosis. Thus, PIQ is a novel protein that may function to bridge a crosstalk between p53 and calmodulin-regulated cellular processes. We further show that PIQ expression is up-regulated in a number of primary colorectal and gastric tumors when compared with matching normal tissues, suggesting that PIQ may be involved in tumorigenesis and could serve as a valuable diagnostic/prognostic marker for gastrointestinal tumors.
Stromelysin-3 Is a Potent Negative Regulator of Adipogenesis Participating to Cancer Cell-Adipocyte Interaction/Crosstalk at the Tumor Invasive Front
Authors: Andarawewa Kumari L. , Motrescu Elena R. , Chenard Marie-Pierre , Gansmuller Anne , Stoll Isabelle , Tomasetto Catherine , Rio Marie-Christine
Published: December 2005

The initial invasive processes during cancer development remain largely unknown. Stromelysin-3/matrix metalloproteinase 11 (ST3/MMP11) is associated with tumor invasion and poor prognosis. We present novel evidence that adipocytes present at human breast tumor invasive front are induced by cancer cells to express ST3. Using mouse syngeneic model, light and electron microscopy showed that in ST3-deficient mice but not in wild-type mice, forced cancer cell-adipocyte interaction/crosstalk results in adipocyte membrane alteration, allowing cancer cell fat infiltration and death. Thus, adipocytes are involved in initial cancer cell survival into connective tissue, and this effect is ST3 mediated. This suggested that ST3 might play a role in adipocyte metabolism. Accordingly, ST3-deficient mice exhibited fat excess and increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte protein 2 (aP2) adipogenic markers, indicating that, in vivo, ST3 negatively regulates fat homeostasis. Moreover, ST3-deficient mouse embryonic fibroblasts exhibited a dramatic enhanced potential to differentiate into adipocytes associated with increased PPARγ and aP2 expression, and recombinant ST3 treatment reverted their differentiation. Thus, in vitro, ST3 reduces adipocyte differentiation in an autocrine manner. High fibroblasts/adipocytes ratio is a stroma feature, and peritumoral fibroblast origin remains debated. Our results support the concept that invading cancer cells aberrantly restore the negative ST3 function on adipogenesis into proximal adipocytes/preadipocytes, leading to the accumulation/maintenance of a particular peritumoral fibroblast subpopulation. Accordingly, in human breast tumors, we observed that ST3-expressing peritumoral fibroblasts are distinct from α-smooth muscle actin-expressing myofibroblasts. This constitutes the first report of implication of a MMP in cancer cell-adipocyte interaction/crosstalk during early steps of connective tissue invasion.
The Syk Tyrosine Kinase Localizes to the Centrosomes and Negatively Affects Mitotic Progression
Authors: Zyss Déborah , Montcourrier Philippe , Vidal Benjamin , Anguille Christelle , Mérezègue Fabrice , Sahuquet Alain , Mangeat Paul H. , Coopman Peter J.
Published: December 2005

We showed previously that the spleen tyrosine kinase Syk is expressed by mammary epithelial cells and that it suppresses malignant growth of breast cancer cells. The exact molecular mechanism of its tumor-suppressive activity remains, however, to be identified. Here, we show that Syk colocalizes and copurifies with the centrosomal component γ-tubulin and exhibits a catalytic activity within the centrosomes. Moreover, its centrosomal localization depends on its intact kinase activity. Centrosomal Syk expression is persistent in interphase but promptly drops during mitosis, obviously resulting from its ubiquitinylation and proteasomal degradation. Conversely, unrestrained exogenous expression of a fluorescently tagged Discosoma sp. red fluorescent protein (DsRed)-Syk chimera engenders abnormal cell division and cell death. Transient DsRed-Syk overexpression triggers an abrupt cell death lacking hallmarks of classic apoptosis but reminiscent of mitotic catastrophe. Surviving stable DsRed-Syk–transfected cells exhibit multipolar mitotic spindles and contain multiple abnormally sized nuclei and supernumerary centrosomes, revealing anomalous cell division. Taken together, these results show that Syk is a novel centrosomal kinase that negatively affects cell division. Its expression is strictly controlled in a spatiotemporal manner, and centrosomal Syk levels need to decline to allow customary progression of mitosis.
BRCA1 Promoter Methylation in Sporadic Breast Cancer Is Associated with Reduced BRCA1 Copy Number and Chromosome 17 Aneusomy
Authors: Wei Minjie , Grushko Tatyana A. , Dignam James , Hagos Fitsum , Nanda Rita , Sveen Lise , Xu Jinhua , Fackenthal James , Tretiakova Maria , Das Soma , Olopade Olufunmilayo I.
Published: December 2005

To explore the molecular mechanisms for the similarities between inherited and noninherited forms of breast cancer, we tested the hypothesis that inactivation of BRCA1 by promoter hypermethylation is associated with reduced gene copy number and chromosome 17 aneusomy as observed in tumors from BRCA1 mutation carriers. Using a combination of methylation-specific PCR analysis and fluorescence in situ hybridization, we observed varying degrees of promoter methylation in 39 of 131 (29.8%) primary tumors. Despite significant tumor heterogeneity, mean copy numbers of BRCA1 and CEP17 per cell were lower in methylated cases compared with unmethylated cases [1.78 versus 2.30 (P = 0.001) and 1.85 versus 2.29 (P = 0.005), respectively]. Methylation was more frequently observed in younger women (P = 0.05) with high-grade (P = 0.001), estrogen receptor–negative (P = 0.04), and progesterone receptor–negative (P = 0.01) tumors. Moreover, methylation was associated with reduced or absent BRCA1 transcripts, which was reversible in the heavily BRCA1-methylated cell line UACC3199 following treatment with 5-aza-2′-deoxycytidine and trichostatin A. We identified five CpGs at positions −533, −355, −173, −21, and +44 as critical in the reexpression of BRCA1. We conclude that BRCA1 methylation contributes to a subset of sporadic breast cancers with the resulting molecular and clinicopathologic phenotype similar to that of hereditary BRCA1-associated breast cancers. Our data support a model of carcinogenesis in which BRCA1 promoter methylation may serve as a “first hit,” much like an inherited germ line mutation, and promote tumor progression down a restricted set of molecular pathways.