bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of the isothermal nucleation and growth parameters for the crystallization of thin Ge2Sb2Te5 films
Authors: Ruitenberg G. , Petford-Long A. K. , Doole R. C.
Published: August 2002

The isothermal crystallization of thin amorphous Ge2Sb2Te5 films, sandwiched between Si3N4 dielectric layers, was followed in real time using in situ transmission electron microscopy. A temperature-dependent incubation time is observed. After this incubation time, the crystallization is found to follow Johnson–Mehl–Avrami–Kolmogorov (JMAK) transformation kinetics. The JMAK parameters were determined, as well as the individual nucleation and growth parameters. The relationships between the JMAK parameters and the nucleation and growth parameters were tested and found to be valid. Nucleation was found to occur at the interfaces with the dielectric layers. The average grain size after crystallization did not show appreciable temperature dependence in the temperature range investigated.
Stability of an electrodynamic suspension
Authors: Filatov Alexei V. , Maslen Eric H. , Gillies George T.
Published: August 2002

Previously, the authors have described a method of dynamically stabilized noncontact electromagnetic suspension of rotating bodies. The method makes use of the dynamic interaction between stationary and rotating sets of conductors and permanent magnets. The validity of this method has been demonstrated by building and testing a prototype in which noncontact suspension of a 3.2 kg rotor was achieved when it rotates at speeds above 18 Hz. A stability condition for that method of suspension was obtained with certain simplifying assumptions. One of these assumptions was that the inductive component of the stationary conductors is negligible. Here, we present modified stability conditions which take the inductance of the stationary conductors into consideration. One of the predicted effects is that nonzero inductance may cause significant reduction of the minimum stable levitation speed. Consequently, careful choice of the electrical properties of the stationary coils may significantly enhance the performance of the suspension.
Dependence of threshold thickness of crystallization and film morphology on film processing conditions in poly(vinylidene fluoride–trifluoroethylene) copolymer thin films
Authors: Xia Feng , Razavi B. , Xu Haisheng , Cheng Z.-Y. , Zhang Q. M.
Published: August 2002

In spin-cast films of poly(vinylidene fluoride–trifluoroethylene) on metalized silicon substrate, there exists a threshold thickness of crystallization dth, below which the crystallinity drops precipitously. Due to the direct link between the crystallinity and functional properties in the polymer, there is a corresponding large change in the film ferroelectric properties, including the dielectric constant, the polarization level, and polarization switching speed, as the thickness is reduced to below dth. Detail microstructure studies show that this threshold thickness is controlled by the stable crystal lamellar size along the film thickness direction. By varying the film processing condition to reduce the crystal lamellar size in the thickness direction, dth can be reduced markedly. As a result, better ferroelectric responses were obtained in ultrathin films.
Stability conditions for the traveling pulse: Modifying the restitution hypothesis
Authors: Cytrynbaum Eric , Keener James P.
Published: August 2002

As a simple model of reentry, we use a general FitzHugh–Nagumo model on a ring (in the singular limit) to build an understanding of the scope of the restitution hypothesis. It has already been shown that for a traveling pulse solution with a phase wave back, the restitution hypothesis gives the correct stability condition. We generalize this analysis to include the possibility of a pulse with a triggered wave back. Calculating the linear stability condition for such a system, we find that the restitution hypothesis, which depends only on action potential duration restitution, can be extended to a more general condition that includes dependence on conduction velocity restitution as well as two other parameters. This extension amounts to unfolding the original bifurcation described in the phase wave back case which was originally understood to be a degenerate bifurcation. In addition, we demonstrate that dependence of stability on the slope of the restitution curve can be significantly modified by the sensitivity to other parameters (including conduction velocity restitution). We provide an example in which the traveling pulse is stable despite a steep restitution curve.
Electron-beam-induced deposition with carbon nanotube emitters
Authors: Dong Lixin , Arai Fumihito , Fukuda Toshio
Published: August 2002

Electron-beam-induced deposition (EBID) is performed with multiwalled carbon nanotube emitters that are assembled to atomic force microscope cantilevers through nanorobotic manipulations. A typical experiment shows that under 120 V bias, field emission current 2 μA occurs from a nanotube emitter. In comparison with conventional EBID with a Schottky-type electron gun of a field-emission scanning electron microscope (FESEM) in the same vacuum chamber, the deposition rate of the nanotube emitter reaches up to 12.2% of that of FESEM although the bias and the emission current are only 0.8% and 1.9% of those of FESEM (15 kV and 106 μA). The concept of parallel EBID is also presented.
Hydrogen plasma-enhanced thermal donor formation in n-type oxygen-doped high-resistivity float-zone silicon
Authors: Simoen E. , Claeys C. , Job R. , Ulyashin A. G. , Fahrner W. R. , De Gryse O. , Clauws P.
Published: August 2002

The impact of plasma hydrogenation on the subsequent formation of thermal donors at 450 °C in n-type oxygen-doped high-resistivity float-zone silicon is investigated by a combination of electrical and spectroscopic techniques. It is shown that the increase of the doping concentration can be explained by the creation of two sets of donors. The first one is the classical double oxygen thermal donors (OTDs), which are introduced with a nearly uniform concentration profile across the sample thickness, while the second type of donors is shallower and most likely hydrogen related. The latter show a pronounced concentration profile towards the surface and they form and disappear at a much faster rate than the OTDs at 450 °C.
High-responsivity submicron metal-semiconductor-metal ultraviolet detectors
Authors: Palacios T. , Monroy E. , Calle F. , Omnès F.
Published: August 2002

Metal-semiconductor-metal ultraviolet (UV) detectors with finger width and pitch ranging from 0.5 to 4 μm have been fabricated on GaN. A superlinear enhancement of responsivity is observed when scaling down, in agreement with a model that includes optical absorption and the variation of the space-charge regions with bias. No degradation is found in terms of UV/visible contrast or photocurrent linearity.
Modal analysis of second-harmonic generation of shear horizontal modes in an elastic plate
Authors: Deng Mingxi , Liu Zhenqing
Published: August 2002

A modal analysis is presented to derive second-harmonic generation of shear horizontal modes in an elastic plate. Under second-order perturbation the second harmonics will generate along with shear horizontal mode propagation due to the bulk elastic nonlinearity of the plate material. The fields of the second harmonics are regarded as superpositions of fields of harmonic frequency Lamb modes. The analysis results show that the field component of harmonic frequency Lamb modes may have a cumulative growth effect as its phase velocity exactly or approximately equals that of shear horizontal modes. The exact solution to the second harmonics is obtained.
Growth and optical studies of two-dimensional electron gas of Al-rich AlGaN/GaN heterostructures
Authors: Nam K. B. , Li J. , Nakarmi M. L. , Lin J. Y. , Jiang H. X.
Published: August 2002

Al 0.5 Ga 0.5 N/GaN heterostructures were grown by metalorganic chemical vapor deposition on sapphire substrates. Time-resolved photoluminescence (PL) emission spectroscopy was employed to study the optical properties of these samples. A very strong and broad emission band was observed under high excitation intensity (Io=104 W/cm2) and its spectral peak position varies from 3.382 and 3.444 eV (at 10 K) depending on the top AlGaN layer thickness (d). This emission line is related to the recombination between the two-dimensional electron gas (2DEG) and photoexcited holes in Al0.5Ga0.5N/GaN heterostructures. In a sharp contrast to the AlGaAs/GaAs heterostructure system in which the PL emission line associated with the 2DEG is observable only at low temperatures (T<20 K), the 2DEG emission line in Al0.5Ga0.5N/GaN heterostructures is observable at temperature as high as 220 K. This is due to the strong piezoelectric polarization and deep triangular potential resulting from the large band offset in high Al content AlGaN/GaN heterostructures. For AlxGa1−xN/GaN (x=0.5) heterostructures with d=110 Å, five emission lines were resolved at 10 K at emission energies 70, 97, 126, 157, and 216 meV below the GaN bound exciton peak under a low excitation intensity (10 W/cm2), due to the recombination between the 2DEG electrons in different subbands and photoexcited holes.
Femtosecond three-pulse photon echo and population grating studies of the optical properties of CdTe/ZnSe quantum dots
Authors: Van Dao Lap , Lowe Martin , Hannaford Peter , Makino Hisao , Takai Toshiaki , Yao Takafumi
Published: August 2002

Femtosecond three-pulse two-color photon echo and population grating (PG) techniques have been used to characterize CdTe quantum dots (QDs) grown on ZnSe by molecular beam epitaxy. The time evolution of the PG signal exhibits a fast decay (2.5–3 ps), which is attributed to migration and tunneling of photoexcited carriers to neighboring QDs, followed by a slow decay (∼20 ps for small dots and >100 ps for large dots), which is ascribed to the lifetime of excitons in the quantum dots. The three-pulse photon echo intensity versus population time can be used to deduce values for the homogeneous broadening (Γh=0.8–1.2 meV) and the exciton binding energy (∼13 meV). A weak dependence of these quantities on the detection wavelength is associated with a difference in dot sizes, which alters the coupling between the exciton and the acoustic phonons.
Near-infrared intersubband absorption in GaN/AlN quantum wells grown by molecular beam epitaxy
Authors: Iizuka Norio , Kaneko Kei , Suzuki Nobuo
Published: August 2002

GaN/AlN multiple-quantum-well structures were grown by molecular beam epitaxy. Abrupt interfaces and good periodicity were confirmed. Absorption measurements indicated that intersubband absorptions occurred at wavelengths of 1.3–2.2 μm. Spectral fits by Lorentzians suggested that the well thicknesses fluctuated by two monolayers. The linewidths of the individual fits were as narrow as 80–120 meV. The characteristics of the absorption saturation were investigated at a wavelength of 1.46 μm. A relaxation time of 400 fs and saturation energy density of 0.5 pJ/μm2 were obtained. These results are promising for realizing ultrafast optical switches with energy consumption of the picojoule order.
Excitation and de-excitation properties of silicon quantum dots under electrical pumping
Authors: Irrera A. , Pacifici D. , Miritello M. , Franzò G. , Priolo F. , Iacona F. , Sanfilippo D. , Di Stefano G. , Fallica P. G.
Published: August 2002

In this work, the stationary and time-resolved electroluminescence (EL) properties of Si quantum dots embedded within a metal–oxide–semiconductor device are investigated. In particular, we measured the excitation cross section of Si nanocrystals under electrical pumping, finding a value of 4.7×10−14 cm2 which is two orders of magnitude higher with respect to the excitation cross section under 488 nm optical pumping. We also studied the radiative and nonradiative decay processes occurring in these devices by measuring the time evolution of the EL signal. We demonstrate that the mechanism responsible for the emission is the same under both electrical and optical pumping. The overall quantum efficiency of the electrical pumping is estimated to be two orders of magnitude higher than the quantum efficiency for optical pumping in all the studied temperature ranges.
Effectively left-handed (negative index) composite material
Authors: Fredkin D. R. , Ron A.
Published: August 2002

We show that a layered material, with alternating layers having negative permittivity (ε<0) and negative permeability (μ<0), responds to electromagnetic fields in many ways like a homogeneous left-handed material with ε<0 and μ<0. In particular, such a layered structure supports electromagnetic waves with group velocity antiparallel to the phase velocity. However, phase-sensitive measurements of the scattering matrix would distinguish the material from a homogeneous left-handed material. The appearance of a mode with positive index of refraction (right-handed mode) at frequencies for which ε and μ are negative is a surprising feature.
Photoemission study of Zr- and Hf-silicates for use as high-κ oxides: Role of second nearest neighbors and interface charge
Authors: Opila R. L. , Wilk G. D. , Alam M. A. , van Dover R. B. , Busch B. W.
Published: August 2002

We show a systematic trend of x-ray photoelectron binding energy shifts for Zr- and Hf-silicates, which are related to the composition of the films. The binding energy for the core photoelectrons can shift by up to 2 eV, depending on the relative electronegativities of the second nearest-neighbor elements. Understanding these shifts helps determine the underlying local electronic and chemical nature of the silicate network. Furthermore, we explain how charge at the dielectric-semiconductor interface can lead to shifts in the measured Si 2p peak binding energy by as much as 1 eV. The direction and magnitude of the binding energy shift can be used to determine the sign and density of the charge at the interface.
Origin of gap states at initial stage oxidation on Si(001)2×1:H and water adsorption on Si(001)2×1: A theoretical study
Authors: Nishida Masahiko
Published: August 2002

Electronic states for top-bridge bonded oxygen on the Si(001)2×1:H surface and for water adsorbed on the Si(001)2×1 surface are calculated by the extended Hückel-type nonorthogonal tight-binding method. It is found that the occurrence of surface states depends strongly on the angle (α) of the Si–O–Si bond formed at a dimer site and that gap states are induced when α>145°. It is also demonstrated that initial water adsorption does not create new gap states, but can quench gap states associated with surface dangling bonds, explaining the experiment.
Passivation effects of alumina insulating layer on C60 thin-film field-effect transistors
Authors: Horiuchi Kazunaga , Nakada Kenji , Uchino Shin , Hashii Shinobu , Hashimoto Akira , Aoki Nobuyuki , Ochiai Yuichi , Shimizu Masaaki
Published: August 2002

A covering of an alumina insulating layer was deposited on the top of a C60 thin-film field-effect transistor (FET) by rf magnetron sputtering with Ar gas, in order to passivate the FET action from the degradation due to oxygen adsorption. The deposited alumina was amorphous and slightly oxygen deficient from the stoichiometry. The stability of FET action in air was considerably improved and no degradation has been detected even for more than one month.
In situ measurement of laser power at the focus of a high numerical aperture objective using a microbolometer
Authors: Viana N. B. , Mesquita O. N. , Mazolli A.
Published: August 2002

We built a simple mercury-based microbolometer to measure “in situ” laser power at the focus of high numerical aperture objectives used in optical microscopy and optical tweezers. With an optical microscope equipped with a high numerical aperture objective, we visualize a mercury droplet immersed in water that is heated by an infrared laser, whose power we want to determine. For a given laser power the mercury droplet reaches the boiling temperature of the water and then jumps, making a precise determination of this point very easy. We solve the heat equation for this system and, using known material parameters and the size of the mercury droplet, we determine the local power of the infrared laser.
Optical and transport properties of an alkali-doped methanofullerene
Authors: Saab A. P. , Stucky G. D. , Srdanov V. I. , Hummelen J. C. , González M. , Wudl F.
Published: August 2002

We examine the effects of monoderivatization on the electronic properties of C60. For this we chose the phenyl-C61-octanoic acid cholesteryl ester, [6,6]PCOCr, whose nonlinear optical properties have been investigated in the past. While the optical absorption spectrum of this methano fullerene is similar to that of C60, substantial differences are observed upon doping with potassium. Similarly, the doping-dependent conductivity of the functionalized fullerene shows two maxima as opposed to the single maximum for C60. The experimental observations are consistent with the doping-induced degeneracy removal of the parent C60 LUMO (t1u) orbital, which in potassium-doped methanofullerene splits into two components separated by about 0.5 eV. We provide experimental evidence that the doping of [6,6]PCOCr proceeds, as in C60, with six consecutive reduction (electron transfer) steps, yielding K6[6,6]PCOCr stoichiometry at the end. The transport in partially doped [6,6]PCOCr thin films occurs by thermally activated hopping of the charge carriers with activation energy Ea≅0.25 eV and hopping probability proportional to the number of unpaired electrons in the reduced molecule.
X-ray and Raman analyses of GaN produced by ultrahigh-rate magnetron sputter epitaxy
Authors: Park Minseo , Maria J.-P. , Cuomo J. J. , Chang Y. C. , Muth J. F. , Kolbas R. M. , Nemanich R. J. , Carlson E. , Bumgarner J.
Published: August 2002

Thick films of GaN were studied by x-ray diffraction and Raman spectroscopy. The GaN thick films were deposited on (0001) sapphire using ultrahigh-rate magnetron sputter epitaxy with typical growth rates as high as 10–60 μm/min. The width of the x-ray rocking curve from the (0002) reflection for the sample produced by this technique is ∼300 arcsec, which is unprecedented for GaN produced by a sputtering-type process. Our recent sample shows an x-ray rocking curve width of 240 arcsec. Only allowed modes were observed in the polarized Raman spectra. The background free carrier concentration is lower than 3×1016 cm−3. The phonon lifetime of the Raman E2(2) mode of the sputtered GaN was comparable to that of bulk single crystal GaN grown by sublimation. The quality of the film was uniform across the wafer. The film was thermally stable upon annealing in N2 ambient. The x-ray and Raman analyses revealed that the sputtered GaN films are of high crystalline quality.
Evidence of a nanomechanical resonator being driven into chaotic response via the Ruelle–Takens route
Authors: Scheible Dominik V. , Erbe Artur , Blick Robert H. , Corso Gilberto
Published: August 2002

Nanomechanical resonators, of importance for signal filtering and transduction, are investigated within the limit of extreme nonlinear excitation. The Ruelle–Takens route establishes the transition of a system into chaos with n frequencies present. By providing a set of three sources, this transition from linear to nonlinear and finally to chaotic response can be traced, and it is found in our experiment. Knowledge of potentially chaotic behavior of nanomechanical systems is crucial for their application. Our resonator system has an overall length of 4 μm and a cross section of about 100 nm×300 nm with natural frequencies of ∼50 MHz.
Mechanism of Tacrine Block at Adult Human Muscle Nicotinic Acetylcholine Receptors
Authors: Prince Richard J. , Pennington Richard A. , Sine Steven M.
Published: August 2002

We used single-channel kinetic analysis to study the inhibitory effects of tacrine on human adult nicotinic receptors (nAChRs) transiently expressed in HEK 293 cells. Single channel recording from cell-attached patches revealed concentration- and voltage-dependent decreases in mean channel open probability produced by tacrine (IC50 4.6 μM at −70 mV, 1.6 μM at −150 mV). Two main effects of tacrine were apparent in the open- and closed-time distributions. First, the mean channel open time decreased with increasing tacrine concentration in a voltage-dependent manner, strongly suggesting that tacrine acts as an open-channel blocker. Second, tacrine produced a new class of closings whose duration increased with increasing tacrine concentration. Concentration dependence of closed-times is not predicted by sequential models of channel block, suggesting that tacrine blocks the nAChR by an unusual mechanism. To probe tacrine's mechanism of action we fitted a series of kinetic models to our data using maximum likelihood techniques. Models incorporating two tacrine binding sites in the open receptor channel gave dramatically improved fits to our data compared with the classic sequential model, which contains one site. Improved fits relative to the sequential model were also obtained with schemes incorporating a binding site in the closed channel, but only if it is assumed that the channel cannot gate with tacrine bound. Overall, the best description of our data was obtained with a model that combined two binding sites in the open channel with a single site in the closed state of the receptor.
Regulation of Murine Airway Surface Liquid Volume by CFTR and Ca2+-activated Cl− Conductances
Authors: Tarran Robert , Loewen Matthew E. , Paradiso Anthony M. , Olsen John C. , Gray Micheal A. , Argent Barry E. , Boucher Richard C. , Gabriel Sherif E.
Published: August 2002

Two Cl− conductances have been described in the apical membrane of both human and murine proximal airway epithelia that are thought to play predominant roles in airway hydration: (1) CFTR, which is cAMP regulated and (2) the Ca2+-activated Cl− conductance (CaCC) whose molecular identity is uncertain. In addition to second messenger regulation, cross talk between these two channels may also exist and, whereas CFTR is absent or defective in cystic fibrosis (CF) airways, CaCC is preserved, and may even be up-regulated. Increased CaCC activity in CF airways is controversial. Hence, we have investigated the effects of CFTR on CaCC activity and have also assessed the relative contributions of these two conductances to airway surface liquid (ASL) height (volume) in murine tracheal epithelia. We find that CaCC is up-regulated in intact murine CF tracheal epithelia, which leads to an increase in UTP-mediated Cl−/volume secretion. This up-regulation is dependent on cell polarity and is lost in nonpolarized epithelia. We find no role for an increased electrical driving force in CaCC up-regulation but do find an increased Ca2+ signal in response to mucosal nucleotides that may contribute to the increased Cl−/volume secretion seen in intact epithelia. CFTR plays a critical role in maintaining ASL height under basal conditions and accordingly, ASL height is reduced in CF epithelia. In contrast, CaCC does not appear to significantly affect basal ASL height, but does appear to be important in regulating ASL height in response to released agonists (e.g., mucosal nucleotides). We conclude that both CaCC and the Ca2+ signal are increased in CF airway epithelia, and that they contribute to acute but not basal regulation of ASL height.
Gene delivery by a steroid‐peptide nucleic acid conjugate
Authors: Rebuffat Alexandre G. , Nawrocki Andrea R. , Nielsen Peter E. , Bernasconi Alessio G. , Bernal‐Mendez Eloy , Frey Brigitte M. , Frey Felix J.
Published: August 2002

We previously introduced a method called steroid‐mediated gene delivery (SMGD), which uses steroid receptors as shuttles to facilitate the nuclear uptake of transfected DNA. Here, we describe a SMGD strategy with peptide nucleic acids (PNAs) that allowed linkage of a steroid molecule to a defined position in a plasmid without disturbing its gene expression. We synthesized and tested several bifunctional steroid derivatives [patent in process of nationalization] and finally selected the compound named DEX‐bisPNA, a molecule consisting of a dexamethasone moiety linked to a PNA clamp (bisPNA) through a 30‐atom chemical spacer. Dex‐bisPNA binds to the glucocorticoid receptor (GR) as well as to reporter plasmids containing the corresponding PNA binding sites, translocates the GR from the cytoplasm into the nucleus, and increases the delivery of plasmid to the nucleus, resulting in enhanced GR‐dependent expression of the reporter gene. The SMGD effect was more pronounced in growth‐arrested cells than in proliferating cells. The specificity for the GR was shown by the reversion of the SMGD effect in the presence of dexamethasone as well as an enhanced expression in GR‐positive cells but not in GR‐negative cells. Thus, SMGD with PNA is a promising strategy for nonviral gene delivery into target tissues expressing specific steroid receptors.
Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells
Authors: Majumder B. , Wahle K.W. J. , Moir S. , Schofield A. , Choe Sun‐Nam , Farquharson A. , Grant I. , Heys S. D.
Published: August 2002

Conjugated linoleic acid (CLA) reduces mammary tumorigenesis in rodent models, induces apoptosis in rodent mammary tumor cell lines, and decreases expression of antiapoptotic bcl‐2 in rat mammary tissue. This investigation focused on the cell mechanisms underlying the antitumor effects of CLA. Changes (mRNA, protein) in expression of major proapoptotic p53, p21WAF1/CIP1, bax, bcl‐Xs genes, and the antiapoptotic bcl‐2 gene were observed in malignant MCF‐7 and MDA‐MB‐231 cells and in benign MCF‐10a human mammary tumor cells in culture. CLA, but not linoleic acid (LA), inhibited proliferation in all cells; CLA mix was most effective. CLA increased DNA damage (apoptosis). CLA increased mRNA expression of p53 and p21WAF1/CIP1 (three‐ to fivefold and twofold, respectively) but either decreased bcl‐2 by 20–30% or had no effect in MCF‐7 and MCF‐10a cells, respectively; protein expression reflected mRNA values. In MDA‐MBA‐231 (mutant p53) cells, mRNA for p53 was not changed, but p21WAF1/CIP1 and bcl‐2 mRNA was increased. Protein expression largely reflected mRNA changes but, surprisingly, CLA completely suppressed mutant p53 protein in MDA‐MB‐231 cells. Apparent antiapoptotic effects of increased bcl‐2 expression in MDAMBA‐231 cells were countered by increased proapoptotic p21WAF1/CIP1, Bax, and Bcl‐Xs proteins. Findings indicate that CLA elicits mainly proapoptotic effects in human breast tumor cells through both p53‐dependent and p53‐independent pathways, according to cell type.
Muscle‐derived interleukin‐6: mechanisms for activation and possible biological roles
Authors: FEBBRAIO MARK A. , PEDERSEN BENTE KLARLUND
Published: August 2002

It has recently been demonstrated that the marked increase in the systemic concentration of cytokine interleukin‐6 (IL‐6) seen with exercise originates from the contracting limb and that skeletal muscle cells per se are the likely source of the production. This review summarizes the possible mechanisms for activation and biological consequences of muscle‐derived IL‐6. It appears that intramuscular IL‐6 is stimulated by complex signaling cascades initiated by both calcium (Ca2+) ‐dependent and ‐independent stimuli. It also seems likely that skeletal muscle produces IL‐6 to aid in maintaining metabolic homeostasis during periods of altered metabolic demand such as muscular exercise or insulin stimulation. It may do so via local and/or systemic effects. This review also explores the efficacy that IL‐6 may be used as a therapeutic drug in treating metabolic disorders such as obesity, type 2 diabetes, and atherosclerosis.—Febbraio, M. A., Pedersen, B. K. Muscle‐derived interleukin 6: mechanisms for activation and possible biological roles. FASEB J. 16, 1335–1347 (2002)
Estrogen regulates development of the somatic cell phenotype in the eutherian ovary
Authors: BRITT KARA L. , KERR JEFF , O'DONNELL LIZA , JONES MARGARET E. E. , DRUMMOND ANN E. , DAVIS SUSAN R. , SIMPSON EVAN R. , FINDLAY JOCK K.
Published: August 2002

Steroids play a critical role in gonadal differentiation in birds, reptiles, and amphibia whereas gonadal differentiation in mammals is thought to be determined by genetic mechanisms. The gonads of female mice incapable of synthesizing estrogens due to disruption of the aromatase gene (ArKO) provide a unique model to test the role of estrogen in regulating the gonadal phenotype. We have shown that in the absence of estrogen, genetically female mice develop testicular tissue within their ovaries. The ovaries develop cells that possess structural and functional characteristics of testicular interstitial cells and of seminiferous tubule‐like structures lined with Sertoli cells. Moreover, the ovaries express mRNA for the testis‐specific Sertoli cell transcription factor Sox 9 and espin protein, which is specific for inter‐Sertoli cell junctions. The development of the testicular tissue in this model can be reverted/postponed by replacing estrogen. When ArKO female mice were fed a diet containing phytoestrogens, the appearance of Leydig and Sertoli cells was postponed and reduced. Furthermore, administration of estradiol‐17J decreased the number of Sertoli and Leydig cells in the ovaries. These findings constitute definitive evidence that estrogen plays a critical role in maintaining female somatic interstitial and granulosa cells in the eutherian ovary.—Britt, K. L., Kerr, J., O'Donnell, L., Jones, M. E. E., Drummond, A. E., Davis, S. R., Simpson, E. R., Findlay, J. K. Estrogen regulates development of the somatic cell phenotype in the eutherian ovary. FASEB J. 16, 1389–1397 (2002)
Differential effects of leptin on thermoregulation and uncoupling protein abundance in the neonatal lamb
Authors: Mostyn Alison , Bispham Jayson , Pearce Sarah , Evens Yvonne , Raver Nina , Keisler Duane H. , Webb Robert , Stephenson Terence , Symonds Michael E.
Published: August 2002

As the role of leptin in energy balance in neonate is unknown, we investigated the effect of acute (2 h) and chronic (7 days) administration of leptin (100 μg/day) on thermoregulation and mitochondrial protein abundance in adipose tissue. The concentration of uncoupling protein (UCP)1 and voltage‐dependent anion channel (VDAC) located on the inner and outer mitochondrial membranes, respectively, were measured. Administration of leptin prevented the normal decline in colonic temperature over the first few hours and days after birth. It subsequently accelerated the loss of both mRNA and protein for UCP1 but had no effect on VDAC abundance. At seven days of age, colonic temperature was correlated strongly with both mRNA abundance and thermogenic potential of UCP1 in leptin‐treated but not control lambs, indicating more effective use of UCP1 for heat production following leptin administration. Leptin had no effect on weight gain or adipose tissue deposition; at one day of age only, leptin mRNA was correlated positively with adipose tissue weight. In conclusion, leptin administration to neonatal lambs improves thermoregulation and promotes the loss of UCP1 in brown adipose tissue.
Expression of Concern: Bcl‐2 overexpression in human melanoma cells increases angiogenesis through VEGF mRNA stabilization and HIF‐1mediated transcriptional activity
Authors: Iervolino Angela , Trisciuoglio Daniela , Ribatti Domenico , Candiloro Antonio , Biroccio Annamaria , Zupi Gabriella , Del Bufalo Donatella
Published: August 2002

The aim of this paper was to study the molecular mechanisms by which bcl‐2 increases hypoxiainduced vascular endothelial growth factor (VEGF) expression. We demonstrated that bcl‐2 overexpression in M14 human melanoma cell line enhances hypoxia‐induced VEGF mRNA stability and promoter activation. In particular, the half‐life of the message was longer in bcl‐2 transfectants (approximately 330 min) than in control cells (approximately 180 min). In addition, bcl‐2 overexpression increased VEGF promoter activity through the hypoxia‐inducible factor‐1 (HIF‐1) transcription factor. Increased HIF‐1α protein expression and DNA binding activity were detected in bcl‐2 overexpressing cells compared with control cells. An enhanced functional activity of secreted VEGF was found both in in vitro and in vivo angiogenic assays, and the use of VEGF specific antibodies validated the role of VEGF on bcl‐2‐induced angiogenesis. Taken together our results indicate that bcl‐2 plays an important role in melanoma angiogenesis, and that VEGF mRNA stabilization and HIF‐1‐mediated transcriptional activity are two important control points in bcl‐2/hypoxia‐induced VEGF expression.
3H‐thymidine is a defective tool with which to measure rates of DNA synthesis
Authors: Hu Valerie W. , Black Gavin E. , Torres‐Duarte Armida , Abramson Fred P.
Published: August 2002

Metabolic incorporation of 3H‐thymidine into cellular DNA is a widely used protocol to monitor rates of DNA synthesis and cell proliferation. However, this radiochemical has also been reported to induce cell‐cycle arrest and apoptosis in addition to DNA damage. Using stable isotope‐labeled thymidine, we demonstrate that 3H‐thymidine induces dose‐dependent inhibition of the rate of DNA synthesis. This inhibition occurred within the first round of replication after addition of the radiolabeled tracer and demonstrates the cytotoxic effects of conventional doses of 3H‐thymidine (typically ≥ 1 μCi/ml). These results thus show that stable isotope methods are superior to radioisotopes for determining rates of DNA synthesis and cell replication. Because 3H‐thymidine perturbs the very process it was employed to study, experiments using 3Hthymidine to monitor DNA synthesis and cell proliferation should be interpreted with caution.
Reduced tumor growth, experimental metastasis formation, and angiogenesis in rats with a hyperreactive dopaminergic system
Authors: Teunis Marc A.T. , Kavelaars Annemieke , Voest Emile , Bakker Joost M. , Ellenbroek Bart. A. , Cools Alexander R. , Heijnen Cobi J.
Published: August 2002

Outgrowth of solid tumors requires blood supply to the tumor. Tumor angiogenesis is dependent on the interplay between tumor‐derived angiogenic factors and stromal cells. Recently, it has been shown that the neurotransmitter dopamine is a potent inhibitor of VEGF‐induced angiogenesis. Moreover, there is evidence that patients with schizophrenia have a hyperreactive dopaminergic system and are relatively protected from cancer.

We hypothesized that hyperreactivity of the dopaminergic system is related to reduced angiogenesis and tumor development. Therefore, we investigated tumor growth and angiogenesis in two lines of Wistar rats with high (APO‐SUS) or low (APO‐UNSUS) dopaminergic reactivity. Subcutaneous implants of mammary adenocarcinoma cells (MADB106) in matrigel remained 35% smaller in APO‐SUS rats than in APO‐UNSUS rats (P<0.01). Moreover, APO‐SUS rats developed less lung metastases after i.v. administration of MADB106 tumor cells. Furthermore, hemoglobin content (APO‐SUS: 40.6±7.6; APO‐UNSUS: 76.9±13 mg/dl, P<0.05) and expression of the endothelial determinant PECAM‐1 in tumors from APO‐SUS rats were reduced (APO‐SUS: 37±18; APO‐UNSUS 69±25 units, P<0.01), indicating that reduced angiogenesis is responsible for reduced tumor development in APO‐SUS rats. These results suggest a novel link between dopaminergic reactivity, angiogenesis, and tumor development and may explain part of the individual differences in cancer progression.
Tetrodotoxin prevents motor unit enlargement after partial denervation in rat hindlimb muscles
Authors: Tam S. L. , Archibald V. , Tyreman N. , Gordon T.
Published: August 2002

Findings that increased neuromuscular activity significantly reduced sprouting in partially denervated muscles prompted this present study to determine if the converse is true, namely that reduced activity promotes sprouting and motor unit (MU) enlargement. Partial denervation of rat hindlimb muscles by either the L4 or L5 spinal root avulsion resulted in extensive denervation (> 80%) in tibialis anterior (TA) and medial gastrocnemius (MG) muscles, and moderate denervation (∼50%) in soleus (SOL) and plantaris (PL) muscles. The partially denervated muscles were then subjected to a 4 week programme of normal caged activity or TTX‐induced neuromuscular inactivity. At 1 month, measurement of MU enlargement and quantification of sprouting were evaluated, respectively, by electrophysiological and histochemical means. Analysis of electrophysiological data showed that MU forces were significantly increased in both extensively and moderately denervated muscles 1 month after partial denervation and normal cage activity and that neuromuscular activity blockade by TTX completely abolished the MU enlargement in these partially denervated muscles. Histochemical analysis of sprouting revealed that the number of sprouts was significantly increased after partial denervation and normal cage activity, particularly after extensive denervation. TTX‐induced neuromuscular inactivity dramatically reduced the number of sprouts and increased the number of free endplates in the extensively but not the moderately denervated muscles. These data demonstrate that a reduction in neuromuscular activity mediated by presynaptic blockade of neural action potentials reduces MU enlargement in partially denervated muscles by reducing axonal sprouting.
Disruption of the two‐state membrane potential of striatal neurones during cortical desynchronisation in anaesthetised rats
Authors: Kasanetz Fernando , Riquelme Luis A. , Murer M. Gustavo
Published: August 2002

In anaesthetised animals, the very negative resting membrane potential of striatal spiny neurones (down state) is interrupted periodically by depolarising plateaux (up states) which are probably driven by excitatory input. In the absence of active synaptic input, as occurs in vitro, potassium currents hold the membrane potential of striatal spiny neurones in the down state. Because striatal spiny neurones fire action potentials only during the up state, these plateau depolarisations have been perceived as enabling events that allow information processing through cerebral cortex‐basal ganglia circuits. Recent studies have demonstrated that the robust membrane potential fluctuation of spiny neurones is strongly correlated to the slow electroencephalographic rhythms that are typical of slow wave sleep and anaesthesia. To further understand the impact of cortical activity states on striatal function, we studied the membrane potential of striatal neurones during cortical desynchronised states. Simultaneous in vivo recordings of striatal neurones and the electrocorticogram in urethane‐anaesthetised rats revealed that rhythmic alternation between up and down states was disrupted during episodes of spontaneous or induced cortical desynchronisation. Instead of showing robust two‐state fluctuations, the membrane potential of striatal neurones displayed a persisting depolarised state with fast, low‐amplitude modulations. Spiny neurones remained in this persistent up state until the cortex resumed ∼1 Hz synchronous activity. Most of the recorded neurones exhibited a low firing probability, irrespective of the cortical activity state. Time series analysis failed to reveal significant correlations between the membrane potential of striatal neurones and the desynchronised electrocorticogram. Our results suggest that during cortical desynchronisation continuous uncorrelated excitatory input sustains the membrane potential of striatal neurones in a persisting depolarised state, but that substantial additional input is necessary to impel the neurones to threshold. Our data support that the prevailing cortical activity state determines the duration of the enabling depolarising events that take place in striatal spiny neurones.
Obstacle avoidance during human walking: transfer of motor skill from one leg to the other
Authors: van Hedel H. J. A. , Biedermann M. , Erni T. , Dietz V.
Published: August 2002

The aim of this study was to evaluate whether a newly acquired locomotor skill can be transferred to the mirror condition. Subjects were trained to step over an obstacle on a treadmill, the appearance of which was signalled by an acoustic stimulus, while visual information was prevented. Feedback information about foot clearance was provided by acoustic signals. During two successive runs (each consisting of 100 steps over the obstacle) the same leg was leading (i.e. the leg crossing the obstacle first). In the following third run, the leading and trailing legs were changed. During each of the three successive runs the adaptational changes were analysed by recording leg muscle electromyographic (EMG) activity, joint angle trajectories and foot clearance over the obstacle. The training effect gained between the first and second runs and the transfer to the mirror condition (third run) were evaluated. Adaptational changes of all measures, except ankle joint trajectory, could to a significant extent be transferred to the mirror condition. No side‐specific differences in the amount of transfer were found, neither from the right to the left side, nor vice versa. These observations are at variance with adaptational changes observed during split‐belt walking or one‐legged hopping on a treadmill, where no transfer to the mirror condition occurred. It is assumed that this might be due to the specific requirements of the tasks and the leg muscles involved. While in the split‐belt and hopping experiments leg extensor muscles are mainly involved, leg flexors predominate in the performance of the present task. It is hypothesised that the learning effects observed in the present experiments are mediated at a higher level (e.g. brainstem) of locomotor control.
Modulation of ASIC channels in rat cerebellar purkinje neurons by ischaemia‐related signals
Authors: Allen Nicola J. , Attwell David
Published: August 2002

Acid‐sensing ion channels (ASICs), activated by a decrease of extracellular pH, are found in neurons throughout the nervous system. They have an amino acid sequence similar to that of ion channels activated by membrane stretch, and have been implicated in touch sensation. Here we characterize the pH‐dependent activation of ASICs in cerebellar Purkinje cells and investigate how they are modulated by factors released in ischaemia. Lowering the external pH from 7.4 activated an inward current at −66 mV, carried largely by Na+ ions, which was half‐maximal for a step to pH 6.4 and was blocked by amiloride and gadolinium. The H+‐gated current desensitized within a few seconds, but approximately 30% of cells showed a sustained inward current (11% of the peak current) in response to the maintained presence of pH 6 solution. The peak H+‐evoked current was potentiated by membrane stretch (which occurs in ischaemia when [K+]o rises) and by arachidonic acid (which is released when [Ca2+]i rises in ischaemia). Arachidonic acid increased to 77% the fraction of cells showing a sustained current evoked by acid pH. The ASIC currents were also potentiated by lactate (which is released when metabolism becomes anaerobic in ischaemia) and by FMRFamide (which may mimic the action of related mammalian RFamide transmitters). These data reinforce suggestions of a mechanosensory aspect to ASIC channel function, and show that the activation of ASICs reflects the integration of multiple signals which are present during ischaemia.
Transparency of the bovine corneal stroma at physiological hydration and its dependence on concentration of the ambient anion
Authors: Kostyuk Oksana , Nalovina Oksana , Mubard Turki M. , Regini Justyn W. , Meek Keith M. , Quantock Andrew J. , Elliott Gerald F. , Hodson Stuart A.
Published: August 2002

De‐epithelialised and de‐endothelialised bovine corneal stromas with a hydration of 3.2 equilibrated at 154 mm NaCl and buffered at pH 7.4 had their optical density (400–750 nm) measured. Stromas equilibrated against 10, 20, 30, 50 or 100 mm NaCl made isotonic to 154 mm NaCl by supplementing with sorbitol were progressively more transparent as NaCl increased. Hypertonic equilibration against 300, 600 or 1000 mm NaCl resulted in a progressive loss of transparency compared with 154 mm NaCl. Light scattering as a function of wavelength fitted a λ−3 function well for 10, 30, 50, 100 and 154 mm NaCl preparations between 450 and 650 nm, but not at higher wavelengths. However, hypertonic 300, 600 and 1000 mm NaCl preparations showed a λ−2 dependence in the 450–750 nm range. Experiments with 154 mm NaCl and either 0 or 300 mm sorbitol suggested that the changes in light scattering in hypertonic preparations are unlikely to be caused by osmotic alterations to the stromal keratocytes. Psychophysical studies of the optical transmission function of preparations indicated that corneal stromas dialysed against 154 mm NaCl had usable optical properties, but preparations dialysed against 10 mm NaCl were effectively unable to transmit an image. The results are related to the known increase of fixed negative charge in the corneal matrix when chloride ions are adsorbed onto the matrix. It is suggested that the ordering force between corneal collagen fibrils, generated in part by anion binding, may be crucial to the physiological functioning of the visual system.
Effects of leptin on cat intestinal vagal mechanoreceptors
Authors: Gaigé Stéphanie , Abysique Anne , Bouvier Michel
Published: August 2002

Vagal afferent nerve fibres are involved in the transmission to the central nervous system of information relating to food intake and immune reactions. Leptin is involved in the control of food intake and has specific receptors in afferent vagal neurones. To investigate the role of these receptors, we studied the effects of leptin on single vagal afferent activities from intestinal mechanoreceptors in anaesthetized cats. The activity of 35 intestinal vagal mechanoreceptors was recorded by means of glass microelectrodes implanted in the nodose ganglion. Leptin (10 μg), administered into the artery irrigating the upper part of the intestine, induced activation in 17 units (P < 0.001), inhibition in 8 units (P < 0.05), and had no effect on 10 units. The excitatory effects of leptin were blocked by the endogenous interleukine‐1β receptor antagonist, (Il‐1ra, 250 μg, i.a.). Cholecystokinin (CCK, 10 μg, i.a.) induced an activatory response only in the two types of units which were responsive to leptin alone. When leptin was administered after CCK, its excitatory effects were enhanced and its inhibitory effects were blocked, whereas it had no effect on the units which were not affected by leptin alone. The interactions between leptin and CCK are specific ones, since other substances (phenylbiguanide, a serotoninergic agonist; substance P) known to activate the mechanoreceptors did not modify the effects of leptin. These results indicate that leptin appears to play a role in the control of immune responses and food intake via intestinal vagal afferent nerve fibres and that there is a functional link between leptin and Il‐1β.