bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion of carbon nanotubes with single-molecule fluorescence microscopy
Authors: Lu Q. , Freedman K. O. , Rao R. , Huang G. , Lee J. , Larcom L. L. , Rao A. M. , Ke P. C.
Published: November 2004

Single walled carbon nanotubes (SWNTs) are a promising gene and drug delivery system since their physical dimensions mimic nucleic acids. Towards this aim, the hydrophobicity of SWNTs was averted by coating with ribonucleic acid (RNA) polymer [poly(rU)] or bovine serum albumin (BSA) and the consequent diffusion of these synthetic-biomolecular hybrids was studied by single-molecule fluorescence microscopy. The diffusion coefficient for SWNT-poly(rU) was measured at 0.374±0.045μm2∕s and for SWNT-BSA it was 0.442±0.046μm2∕s. Our diffusion study provides a fundamental guidance to gene delivery using SWNT as transporters.
High anisotropy of lateral alignment in multilayered (In,Ga)As∕GaAs(100) quantum dot structures
Authors: Wang Zh. M. , Churchill H. , George C. E. , Salamo G. J.
Published: November 2004

A formation process for long chains of quantum dots during the molecular-beam epitaxial growth of (In,Ga)As∕GaAs(100) multilayers is presented. The morphology evolution monitored by atomic force microscopy for a series of (In,Ga)As layers demonstrates that the highly anisotropic lateral alignment of dots is gradually developed as the result of the strain field interaction mediated by the GaAs spacer coupled with the anisotropic surface kinetics that occurs during capping the dots. The dot-chain structure, providing unique properties of its own, is demonstrated to serve as a template for the spatially controlled growth of strained quantum dots in general.
Spectrally resolved spontaneous emission patterns of oxide-confined vertical-cavity surface-emitting lasers
Authors: Lu T. C. , Hsu W. C. , Chang Y. S. , Kuo H. C. , Wang S. C.
Published: November 2004

Spectrally resolved spontaneous emission patterns of oxide-confined vertical-cavity surface-emitting lasers under the subthreshold condition were investigated. The spontaneous emission mode patterns show clear and stable Hermite–Gaussian modes and high-order Laguerre–Gaussian modes associated with a distinct spectrum. The coexistence of two sets of identical low-order Hermite–Gaussian modes with different spot sizes reveals the presence of two cavity configurations. The data on mode evolution and spot size variation reveal that the modes with larger spots are supported by the cavity with the carrier-induced aperture, and become the dominant modes above the laser threshold; the modes associated with smaller spots are considered to have been formed by the cavity with the oxidized aperture and are suppressed above the threshold.
Motion of guiding center drift atoms in the electric and magnetic field of a Penning trap
Authors: Kuzmin S. G. , O’Neil T. M.
Published: November 2004

The ApparaTus for High precision Experiment on Neutral Antimatter and antihydrogen TRAP collaborations have produced antihydrogen atoms by recombination in a cryogenic antiproton-positron plasma. This paper discusses the motion of the weakly bound atoms in the electric and magnetic field of the plasma and trap. The effective electric field in the moving frame of the atom polarizes the atom, and then gradients in the field exert a force on the atom. An approximate equation of motion for the atom center of mass is obtained by averaging over the rapid internal dynamics of the atom. The only remnant of the atom internal dynamics that enters this equation is the polarizability for the atom. This coefficient is evaluated for the weakly bound and strongly magnetized (guiding center drift) atoms understood to be produced in the antihydrogen experiments. Application of the approximate equation of motion shows that the atoms can be trapped radially in the large space charge field near the edge of the positron column. Also, an example is presented for which there is full three-dimensional trapping, not just radial trapping. Even untrapped atoms follow curved trajectories, and such trajectories are discussed for the important class of atoms that reach a field ionization diagnostic. Finally, the critical field for ionization is determined as an upper bound on the range of applicability of the theory.
Electronic structure and magnetic properties of Al1−xMnxN alloys
Authors: de Paiva R. , Nogueira R. A. , Alves J. L. A.
Published: November 2004

We apply a first-principles method based on the density functional theory within the local spin-density approximation, and the full-potential linear augmented plane-wave method, to calculate the electronic structure and magnetic properties of dilute magnetic Al1−xMnxN alloys in the zinc-blende phase. The analyses of the band structures, density of states, total energy, exchange interactions, and magnetic moments reveal that Al1−xMnxN alloys may exhibit half-metallic ferromagnetism, that the valence band is ferromagnetically coupled to the Mn atoms, and that the total magnetization of the cell is 4.0μB, which does not change with Mn concentration.
A note on the small oscillation regimes of rotating liquid bridges: Transition from surface to internal wave modes
Authors: Gañán-Calvo A. M. , Montanero J. M.
Published: November 2004

An analysis of the small oscillation modes of rotating liquid bridges is carried out. The study is performed in the particular conditions when both surface and internal wave mode frequencies almost coincide for a certain meridional and azimuthal wave number. The critical values of the rotation speed and the natural frequencies for which this transitional condition takes place are obtained numerically as a function of the parameters characterizing the fluid configuration. The influence of both the outer bath and the liquid bridge equilibrium shape on the transition is analyzed. Analytical expressions providing the critical values of the rotation speed and the natural frequencies are obtained for cylindrical liquid bridges.
Quantized energy cascade statistics model of fully developed turbulence
Authors: Guo Jie , Zheng Ning
Published: November 2004

In this paper, it is proposed that the modeling of the inertial ranges up to the integral scale of fully developed turbulence can be described by eddies system that is characterized by a continuous energy flux cascade which obeys Fermi–Dirac statistics distribution. Both ways of introducing the Fermi–Dirac distribution characteristic into modeling of fully developed turbulence energy cascade are suggested. One is based on β model. The key viewpoint is that the turbulent fluctuations reach a statistically quasiequilibrium state which is characterized by a continuous energy flux cascade from large to small scales, a fraction β″ of the total space obeys Fermi–Dirac distribution. Another one is based on a hierarchy of fluctuation structures. The main feature of the model predictions is the term of the denominator characteristic of the Fermi–Dirac distribution, where an effective temperature is defined with the turbulent fluctuation energy. The main argument which is in favor of this model is to agree with experimental data up to the integral scale that generally departs from homogeneous scaling. The predictions of the quantized energy cascade statistics model for second-order as well as higher-order structure functions and energy spectrum are in agreement with experimental data. The model predictions extend over a much wider range of scales with respect to the inertial range, satisfy strictly generalized extended self-similarity, and obey extended self-similarity at the precision of experiment. So, this model may explain some departure from homogeneous scaling around the inertial ranges up to the integral scale.
Can turbophoresis be predicted by large-eddy simulation?
Authors: Kuerten J. G. M. , Vreman A. W.
Published: November 2004

Direct numerical simulation (DNS) and large-eddy simulation (LES) of particle-laden turbulent channel flow, in which the particles experience a drag force, are performed. In this flow turbophoresis leads to an accumulation of particles near the walls. It is shown that the turbophoresis in LES is reduced, in case the subgrid effects in the particle equations of motion are ignored. To alleviate this problem an inverse filtering model is proposed and incorporated into the particle equations. The model is shown to enhance the turbophoresis in actual LES, such that a good agreement with the DNS prediction is obtained.
Friction drag reduction achievable by near-wall turbulence manipulation at high Reynolds numbers
Authors: Iwamoto Kaoru , Fukagata Koji , Kasagi Nobuhide , Suzuki Yuji
Published: November 2004

The Reynolds-number dependence of the drag reduction achievable by diminishing to zero the near-wall turbulent velocity fluctuations is clarified. This reduction could be obtained by a virtual active feedback control system. The formula derived suggests that large drag reduction can be attained even at high Reynolds numbers if turbulence fluctuations adjacent to the wall are completely damped. For example, 35% drag reduction rate can be obtained at Reτ=105 if the turbulence only below y+=10 vanishes. Thus, the active feedback control strategy, which has been studied mostly at low Reynolds numbers, would be much promising even in high Reynolds number flows of real applications. Results from the direct numerical simulation of turbulent channel flow at a Reynolds number of Reτ=642 are also presented to clarify the phenomena in the controlled flow.
Instabilities between rotating and stationary parallel disks with suction
Authors: Rémy David , Gauthier Georges , Buisine Daniel
Published: November 2004

From visualizations, we study the patterns’ formation of the flow in a stationary cylinder driven by a rotating bottom disk when central suction is applied. That creates an annular axial jet at the cavity periphery which destabilizes and gives rise to instability patterns. We distinguish two types of instability patterns and study more particularly the one which takes place in the boundary layer of the cylindrical wall.
Theoretical and experimental studies of kinetic equilibrium and stability of the virtual cathode in an electron injected inertial electrostatic confinement device
Authors: Nebel R. A. , Stange S. , Park J. , Taccetti J. M. , Murali S. K. , Garcia C. E.
Published: November 2004

This paper explores the electron-electron two-stream stability limit of a virtual cathode in spherical geometry. Previous work using a constant density slab model [R. A. Nebel and J. M. Finn, Phys. Plasmas 8, 1505 (2001)] suggested that the electron-electron two-stream would become unstable when the well depth of the virtual cathode was 14% of the applied voltage. However, experimental tests on INS-e have achieved virtual cathode fractional well depths ∼60% with no sign of instability. Here, studies with a spherical gridless particle code indicate that fractional well depths greater than 90% can be achieved without two-stream instabilities. Two factors have a major impact on the plasma stability: whether the particles are reflected and the presence of angular momentum. If the particles are reflected then they are guaranteed to be in resonance with the electron plasma frequency at some radius. This can lead to the two stream instabilities if the angular momentum is small. If the angular momentum is large enough it stabilizes the instability much the same way as finite temperature stabilizes the two-stream instability in a slab.
Effects of fire severity and season of burn on Betula glandulosa growth dynamics
Authors: de Groot William J. , Wein Ross W.
Published: November 2004

Betula glandulosa survives over a wide range of North American fire regimes by resprouting from the rhizome. Over-winter root carbohydrate reserves are important to sprout production and growth in the following spring. Nursery and field experiments were conducted to examine the effects of seasonal clipping and fire severity (lethal heat applied to different soil depths) on B. glandulosa sprouting and growth, and seasonal burning and clipping on over-winter root carbohydrate storage. Low fire severity increased sprout numbers, and low fire severity in spring caused a large increase in height growth and above-ground biomass production over a 2-year period. Mortality rates increased sharply with higher levels of fire severity. Over-winter total non-structural carbohydrate (TNC) concentrations in roots were significantly higher in plants burned immediately after leaf-flush than in mid-summer burned plants. None of the other seasonal burning or clipping treatments significantly influenced over-winter root TNC. Post-disturbance sprout growth reflected over-winter root TNC levels. B. glandulosa survives a wide range of fire frequencies by growing in plant communities that are most likely to burn in spring or autumn, and seldom burn in summer. This provides the greatest opportunity for maximum over-winter TNC storage. As well, high soil moisture after snowmelt ensures spring fires are almost always of low severity, which promotes increased sprout production, height growth and above-ground biomass.
Fire spread in canyons
Authors: Viegas Domingos Xavier , Pita Luis Paulo
Published: November 2004

Canyons or ridges are associated with a large number of fatal accidents produced during forest fires all over the world. A contribution to the understanding of fire behaviour in these terrain conditions is given in this paper. The basic geometrical parameters of the canyon configuration are described. An analytical model assuming elliptical growth of point ignition fires and constant values of rate of spread is proposed. A non-dimensional formulation to transfer results from analytical, numerical, laboratory or field simulations to other situations is proposed. An experimental study at laboratory scale on a special test rig is described. A wide set of canyon configurations were covered in the experimental program. In spite of the relatively small scale of the experiments they were able to put in evidence some of the main features found in fires spreading in this type of terrain. They show that in practically all cases the rate of spread of the fire front is non-constant. On the contrary, the fire has a dynamic behaviour and its properties depend not only on the canyon geometry but on the history of fire development as well. The convection induced by the fire is enhanced by terrain curvature and the fire accelerates causing the well-known blow-up that is associated with canyon fires. The rate of spread of the head fire increases continuously even in the absence of wind or any other special feature or change of boundary conditions that are sometimes invoked to justify such fire behaviour. The results of the present study confirm the predictions of a previous numerical study of the flow and fire spread in canyons that showed the important feedback effect of the fire on the atmospheric flow and how this affects fire behaviour in canyons. Results from a field experiment carried out in a canyon-shaped plot covered by tall shrubs were used to validate the laboratory scale experiments. Case studies related to fatal accidents that occurred in canyon-shaped configurations are analysed and recommendations to deal with this problem are made. It is shown that these accidents may occur even in the absence of special fuel or atmospheric conditions as they are intrinsically related to terrain configuration.
Grazer movements: spatial and temporal responses to burning in a tall-grass African savanna
Authors: Archibald S. , Bond W. J.
Published: November 2004

The consequences of burning on grazer distributions in the landscape were investigated in a savanna system in South Africa. Distribution and extent of fires can be highly variable within and between years, but how this influences patterns of grazing is not well understood. Three years of fire and grazer distribution data from Hluhluwe-Umfolozi Park, KwaZulu Natal were used to describe how animals respond to different burn situations. Animals were attracted to the burnt areas after fires and this resulted in a decrease in grazer densities in unburnt areas. This effect was more pronounced when a larger area of the park had burnt, and increased over time as area burnt increased. Thus, grazing pressure in an area will depend on the size, timing and distribution of fires in a larger spatial context. Fires also seem to promote a more uniform grazing environment: although grazer density overall is higher in areas that have burnt, the grazers are more dispersed in these areas, and grazing at any one point may be less intense than in the unburnt areas (which are grazed patchily). Therefore at the beginning of the wet season—a key time of year for grass growth—fires are acting to decrease grazing pressure at any one point in both burnt and unburnt areas. The presence of fire in grazing systems could affect grass community composition because fire alters the intensity and frequency of utilisation of the grass sward.
Flammability of native understory species in pine flatwood and hardwood hammock ecosystems and implications for the wildland - urban interface
Authors: Behm Anna L. , Duryea Mary L. , Long Alan J. , Zipperer Wayne C.
Published: November 2004

Six understory species from five pine flatwood sites and six understory species from five hardwood hammock sites were harvested for biomass analyses to compare potential flammability between two ecosystems in the south-eastern coastal plain of the United States. Plant components were separated into live and dead foliage, accumulated litter on and under the plant, and small and large stems. Foliar biomass was further analysed for moisture content, volatile solid content, and energy content. Statistical analyses revealed differences among species and between ecosystems. Serenoa repens plants present a wildfire hazard because they contain greater biomass than other species studied. Ilex glabra and Lyonia ferruginea are also hazardous to wildland–urban interface (WUI) structures because they have greater foliar energy content than other species studied. Callicarpa americana plants present the least wildfire hazard to WUI structures. We conclude that differences in flammability among species exist, but the causes of flammability are different among species. In addition, species in the same genus do not always have the same flammability. Based on measured characteristics, understory plants in pine flatwoods have greater ignitability, sustainability and combustibility than understory plants in hardwood hammocks. However, the measurements for consumability were similar between ecosystems.
Microvessels Promote Motor Nerve Survival and Regeneration Through Local VEGF Release Following Ectopic Reattachment
Authors: BEARDEN SHAWN E. , SEGAL STEVEN S.
Published: November 2004

Objectives: Nerves and blood vessels form a close association during embryogenesis. Growth and guidance factors initially attributed to either nerves or vessels are now known to affect both tissues; prominent among these is vascular endothelial growth factor (VEGF). The authors investigated whether axons would associate with blood vessels in a regenerating system and questioned whether VEGF is integral to neurotization following axotomy.

Methods: In hamsters 8–12 weeks of age, the accessory nerve (CN XI) to the retractor muscle of the cheek pouch was cut and the proximal stump was reattached ectopically onto the muscle. Vascular casting and immunolabeling were used to quantify the extent of neurovascular association during regeneration. A role for VEGF was investigated using immunolocalization of VEGF and its receptor (sVEGFR2) as well as local sequestration of VEGF with soluble receptor (sVEGFR1).

Results: Regenerating axons aligned with microvessels of the vasa nervorum along a “chaperone” region during outgrowth from the reattachment site and while entering the muscle. In this ∼1‐mm region, VEGF protein was expressed by growing microvessels despite a ∼50% reduction (p < .05) in total muscle VEGF concentration. VEGFR2 was expressed by regenerating axons and growth cones. Sequestration of VEGF by sVEGFR1 impaired neurotization by ∼40% (p < .05). The chaperone region ended where regenerating microvessels anastomosed with the native microcirculation and their expression of VEGF protein diminished.

Conclusions: Regenerating axons and blood vessels align during outgrowth from ectopic reattachment. This interaction dissipates as vascular anastomoses form with established microvessels and axons target muscle fibers. Local production of VEGF by growing microvessels supports motor nerve survival and regeneration.
Relative Contributions of α4 and αL Integrins to IL‐4‐Induced Leukocyte Rolling and Adhesion
Authors: EPPIHIMER MICHAEL J. , SUSHKOVA NATALIA , LAVIGNE MARK C.
Published: November 2004

Objective: To delineate the relative contributions of α4 and α L to mediate interleukin‐4 (IL‐4) induced leukocyte rolling, and the subsets of leukocytes that use these pathways to adhere.

Methods: Intravital microscopy was used to examine leukocytes in venules of cremaster muscles of mice receiving intrascrotal injections of IL‐4. α4 and αL monoclonal antibodies (mAbs) were administrated either prior to (prophylactic) or 24 h following (therapeutic) treatment with IL‐4. In addition, fluorescent microspheres coated with mAbs directed against CD4, CD8, or Gr‐1 were injected into mice and the number of subset‐specific adherent leukocytes was measured.

Results: Prophylactic inhibition of α4 and αL integrins prevented IL‐4‐induced leukocyte rolling flux (p < .05) and increased leukocyte rolling velocity twofold (p < .05), respectively, while blocking either integrin eliminated IL‐4‐induced leukocyte adhesion (p < .05). In contrast, therapeutic administration of both anti‐α4 and anti‐αL mAbs was necessary to completely inhibit IL‐4‐induced leukocyte adhesion (p < .05). Furthermore, CD8+ and Gr‐1+ leukocytes utilized α4 and αL to adhere to postcapillary venules, whereas CD4+ leukocytes primarily utilized α4.

Conclusions: Following tissue activation with IL‐4, α4 and αL initiate the attachment and deceleration, respectively, of leukocytes during rolling, and are responsible for mediating the adhesion CD4+, CD8+, Gr‐1+ leukocytes.
Increased Expression of Vascular Endothelial Growth Factor and Capillary Density in Hearts of Spontaneously Hypertensive Rats
Authors: GU JIAN‐WEI , FORTEPIANI LOURDES A. , RECKELHOFF JANE F. , ADAIR THOMAS H. , WANG JULIE , HALL JOHN E.
Published: November 2004

Objective: The role of VEGF in vascular remodeling of target organs exposed to chronic hypertension is poorly understood. The authors compared capillary density (CD), capillary‐to‐fiber ratio (C/F), and VEGF mRNA expression in the hearts (left ventricle [LV]), and skeletal muscles (soleus and anterior tibialis [AT]) of 18‐week‐old male spontaneously hypertensive rats (SHR) and age‐matched male Wistar‐Kyoto (WKY) and Sprague‐Dawley (SD) rats.

Methods: CD or C/F in LV, soleus, and AT of SHR, WKY, and SD rats was determined by analysis of randomly acquired digital images of cryosections stained with FITC‐conjugated GS‐I lectin. VEGF mRNA expressions in the tissues were determined by Northern blot.

Results: VEGF mRNA expressions in LV of SHR were 3.84‐ and 5.05‐fold higher, compared to SD and WKY rats, respectively (n = 6; p < .01). There were no significant differences in VEGF mRNA expression in soleus or AT among SHR, WKY, and SD rats (p > .05). CD in LV of SHR (4975 ± 167) was significantly higher than WKY or SD rats, 4151 ± 169 and 3807 ± 187 mm−2, respectively (p < .05). In LV of SHR, C/F increased (35%) more significantly than CD (increased 20%), compared to WKY rats. CD, or C/F in soleus or AT of SHR was similar to that observed in WKY or SD rats.

Conclusions: VEGF expression, CD, and C/F in the heart (LV) of SHR are significantly increased, compared to WKY and SD rats. The data are consistent with the possibility that VEGF may contribute to capillary growth as a compensatory response to hypertension.
Incorporation of Naïve Bone Marrow Derived Cells into the Vascular Architecture of Brain Tumor
Authors: YUNG YUN C. , CHESHIER SAMUEL , SANTARELLI JUSTIN G. , HUANG ZAN , WAGERS AMY , WEISSMAN IRVING , TSE VICTOR
Published: November 2004

Objective: Neovascularization is essential for tumor growth and invasion. Mounting evidence suggests that tumor cells recruit circulating endothelial progenitor cells to promote vasculogenesis to compliment tumor angiogenesis. This study examines the constitutive role of bone marrow‐derived cells in this process.

Methods: Rat glioma cells were implanted into brains of T‐cell‐depleted knockout mice. At various timepoints after tumor implantation, Naïve bone marrow cells from ubiquitous transgenic mice expressing green fluorescent protein (GFP) were infused into these animals. The incorporation of GFP‐positive cells into the vascular architecture was visualized by fluorescence confocal microscopy in conjunction with the transcription profiles of vascular endothelial growth factor (VEGF) and angiopoietin‐1 and ‐2 (Ang‐1 and Ang‐2).

Results: Of the cells infused, 8 days after tumor implantation, 0.49% were found exclusively sequestered in the vicinity of tumor vessels. This coincided with a decline in the expression of Ang‐1 and a rise in the expression of VEGF and Ang‐2. A few of these cells (0.66 of the 0.49%) localized onto the vascular wall. They resembled endothelial cells and expressed vWF.

Conclusion: The incorporation of bone marrow‐derived unpurified endothelial cells into the tumor vascular bed is both time‐limited and infrequent. These cells may play a supportive rather than a constitutive role in tumor neovascularization.
Phosphorylation of DCC by Fyn mediates Netrin-1 signaling in growth cone guidance
Authors: Meriane Mayya , Tcherkezian Joseph , Webber Christine A. , Danek Eric I. , Triki Ibtissem , McFarlane Sarah , Bloch-Gallego Evelyne , Lamarche-Vane Nathalie
Published: November 2004

Netrin-1 acts as a chemoattractant molecule to guide commissural neurons (CN) toward the floor plate by interacting with the receptor deleted in colorectal cancer (DCC). The molecular mechanisms underlying Netrin-1–DCC signaling are still poorly characterized. Here, we show that DCC is phosphorylated in vivo on tyrosine residues in response to Netrin-1 stimulation of CN and that the Src family kinase inhibitors PP2 and SU6656 block both Netrin-1–dependent phosphorylation of DCC and axon outgrowth. PP2 also blocks the reorientation of Xenopus laevis retinal ganglion cells that occurs in response to Netrin-1, which suggests an essential role of the Src kinases in Netrin-1–dependent orientation. Fyn, but not Src, is able to phosphorylate the intracellular domain of DCC in vitro, and we demonstrate that Y1418 is crucial for DCC axon outgrowth function. Both DCC phosphorylation and Netrin-1–induced axon outgrowth are impaired in Fyn−/− CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1.
Invadolysin
Authors: McHugh Brian , Krause Sue A. , Yu Bin , Deans Anne-Marie , Heasman Sarah , McLaughlin Paul , Heck Margarete M.S.
Published: November 2004

The cell cycle is widely known to be regulated by networks of phosphorylation and ubiquitin-directed proteolysis. Here, we describe IX-14/invadolysin, a novel metalloprotease present only in metazoa, whose activity appears to be essential for mitotic progression. Mitotic neuroblasts of Drosophila melanogaster IX-14 mutant larvae exhibit increased levels of nuclear envelope proteins, monopolar and asymmetric spindles, and chromosomes that appear hypercondensed in length with a surrounding halo of loosely condensed chromatin. Zymography reveals that a protease activity, present in wild-type larval brains, is missing from homozygous tissue, and we show that IX-14/invadolysin cleaves lamin in vitro. The IX-14/invadolysin protein is predominantly found in cytoplasmic structures resembling invadopodia in fly and human cells, but is dramatically relocalized to the leading edge of migrating cells. Strikingly, we find that the directed migration of germ cells is affected in Drosophila IX-14 mutant embryos. Thus, invadolysin identifies a new family of conserved metalloproteases whose activity appears to be essential for the coordination of mitotic progression, but which also plays an unexpected role in cell migration.
SPOTS
Authors: Siegel Richard M. , Muppidi Jagan R. , Sarker Malabika , Lobito Adrian , Jen Melinda , Martin David , Straus Stephen E. , Lenardo Michael J.
Published: November 2004

Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis and prevention of autoimmunity. Although FADD and caspase-8 have been identified as key intracellular mediators of Fas signaling, it is not clear how recruitment of these proteins to the Fas death domain leads to activation of caspase-8 in the receptor signaling complex. We have used high-resolution confocal microscopy and live cell imaging to study the sequelae of early events in Fas signaling. These studies have revealed a new stage of Fas signaling in which receptor ligation leads to the formation of surface receptor oligomers that we term signaling protein oligomerization transduction structures (SPOTS). Formation of SPOTS depends on the presence of an intact Fas death domain and FADD but is independent of caspase activity. Analysis of cells expressing Fas mutations from patients with the autoimmune lymphoproliferative syndrome (ALPS) reveals that formation of SPOTS can be disrupted by distinct mechanisms in ALPS.
Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis
Authors: Bolino Alessandra , Bolis Annalisa , Previtali Stefano Carlo , Dina Giorgia , Bussini Simona , Dati Gabriele , Amadio Stefano , Del Carro Ubaldo , Mruk Dolores D. , Feltri Maria Laura , Cheng C. Yan , Quattrini Angelo , Wrabetz Lawrence
Published: November 2004

Mutations in MTMR2, the myotubularin-related 2 gene, cause autosomal recessive Charcot-Marie-Tooth (CMT) type 4B1, a demyelinating neuropathy with myelin outfolding and azoospermia. MTMR2 encodes a ubiquitously expressed phosphatase whose preferred substrate is phosphatidylinositol (3,5)-biphosphate, a regulator of membrane homeostasis and vesicle transport. We generated Mtmr2-null mice, which develop progressive neuropathy characterized by myelin outfolding and recurrent loops, predominantly at paranodal myelin, and depletion of spermatids and spermatocytes from the seminiferous epithelium, which leads to azoospermia. Disruption of Mtmr2 in Schwann cells reproduces the myelin abnormalities. We also identified a novel physical interaction in Schwann cells, between Mtmr2 and discs large 1 (Dlg1)/synapse-associated protein 97, a scaffolding molecule that is enriched at the node/paranode region. Dlg1 homologues have been located in several types of cellular junctions and play roles in cell polarity and membrane addition. We propose that Schwann cell–autonomous loss of Mtmr2–Dlg1 interaction dysregulates membrane homeostasis in the paranodal region, thereby producing outfolding and recurrent loops of myelin.
Structural and functional analysis of Nup133 domains reveals modular building blocks of the nuclear pore complex
Authors: Berke Ian C. , Boehmer Thomas , Blobel Günter , Schwartz Thomas U.
Published: November 2004

Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) whose complex architecture is generated from a set of only ∼30 proteins, termed nucleoporins. Here, we explore the domain structure of Nup133, a nucleoporin in a conserved NPC subcomplex that is crucial for NPC biogenesis and is believed to form part of the NPC scaffold. We show that human Nup133 contains two domains: a COOH-terminal domain responsible for its interaction with its subcomplex through Nup107; and an NH2-terminal domain whose crystal structure reveals a seven-bladed β-propeller. The surface properties and conservation of the Nup133 β-propeller suggest it may mediate multiple interactions with other proteins. Other β-propellers are predicted in a third of all nucleoporins. These and several other repeat-based motifs appear to be major elements of nucleoporins, indicating a level of structural repetition that may conceptually simplify the assembly and disassembly of this huge protein complex.
Effectiveness of Multilevel (Tongue and Palate) Radiofrequency Tissue Ablation for Patients with Obstructive Sleep Apnea Syndrome
Authors: Steward David L.
Published: November 2004

Objectives: The primary objective is to determine the effectiveness of multilevel (tongue base and palate) temperature controlled radiofrequency tissue ablation (TCRFTA) for patients with obstructive sleep apnea syndrome (OSAS). The secondary objective is to compare multilevel TCRFTA to nasal continuous positive airway pressure (CPAP).

Study Design and Methods: The study is a controlled case series of one investigator's experience with multilevel TCRFTA for patients with OSAS. Twenty‐two subjects with mild to severe OSAS, without tonsil hypertrophy, completed multilevel TCRFTA (mean 4.8 tongue base and 1.8 palate treatment sessions) and had both pre‐ and posttreatment polysomnography. Primary outcomes included change from baseline in apnea/hypopnea index (AHI), daytime somnolence, and reaction time testing measured 2 to 3 months after TCRFTA. Secondary outcomes included change in other respiratory parameters, OSAS related quality of life, and upper airway size. Comparison of 18 patients treated with TCRFTA for mild to moderate OSAS (AHI > 5 and ≤ 40) is made with 11 matched patients treated with nasal CPAP for mild to moderate OSAS.

Results: Multilevel TCRFTA significantly improved AHI (P = .001), apnea index (P = .02), as well as respiratory and total arousal indices (P = .0002 and P = .01). Significant improvement with moderate or large treatment effect sizes were noted for OSAS related quality of life (P = .01) and daytime somnolence (P = .0001), with a trend toward significant improvement in reaction time testing (P = .06), with mean posttreatment normalization of all three outcome measures. Fifty‐nine percent of subjects demonstrated at least a 50% reduction in AHI to less than 20. The targeted upper airway, measured in the supine position, demonstrated a trend toward significant improvement in mean cross sectional area (P = .05) and volume (P = .10). Side effects of TCRFTA were infrequent, mild, and self‐limited. No significant correlation between pretreatment parameters and outcome improvement was noted. Nasal CPAP resulted in significant improvement in AHI (P = .0004) to near normal levels, with an associated improvement in OSAS related quality of life (P = .02) and a trend toward significant improvement in daytime somnolence (P = .06). Reaction time testing demonstrated no significant improvement (P = .75). No significant differences were seen for change in AHI, OSAS related quality of life, daytime somnolence, or reaction time testing between multilevel TCRFTA and CPAP.

Conclusion: Multilevel (tongue base and palate) TCRFTA is a low‐morbidity, office‐based procedure performed with local anesthesia and is an effective treatment option for patients with OSAS. On average, abnormalities in daytime somnolence, quality of life, and reaction time testing demonstrated improvement from baseline and were normalized after treatment. Polysomnographic respiratory parameters also demonstrated significant improvement with multilevel TCRFTA.
Auricular Cartilage Grafts And Nasal Surgery
Authors: Murrell George L.
Published: November 2004

Objective: To illustrate the safety, effectiveness, and versatility of auricular cartilage grafts in nasal surgery.

Study Design: Retrospective chart review of the author's nasal surgery experience for an 8‐year period.

Methods: Five hundred eight rhinoplasties were performed over an 8‐year period. One hundred one of these cases used auricular cartilage grafts as donor material.

Results: Donor cartilage was used in a wide range of grafting techniques: tip grafts, dorsal onlays, spreader grafts, septal replacements, alar battens, composite grafts, etc. The average follow up was 12 months. The complication rate was low. Five patients experienced complications involving the auricular cartilage graft or its donor site. No patients experienced graft resorption or infection. Donor site morbidity was limited. No auricular infections or hematomas were observed.

Conclusion: Septal cartilage is usually the first choice as donor material in nasal surgery; however, when indicated, auricular cartilage grafts can serve as a safe, effective, and versatile alternative. This conclusion is supported by their successful use in a wide variety of surgical techniques, with long‐term follow‐up. The author feels strongly that autografts should be favored over alloplastic material. Alloplastic grafts continue to present a risk of infection over the entire life of their use. When a rhinoplasty is performed skillfully with a cartilage autograft, time becomes an ally of the surgeon rather than an enemy.
Surgical Management of Chronic Sinusitis in Children
Authors: Ramadan Hassan H.
Published: November 2004

Objectives/Hypothesis: The objective was to compare three common surgical modalities in children for the treatment of chronic sinusitis that is refractory to medical management.

Study Design: Prospective nonrandomized study in a pediatric otolaryngology tertiary service.

Methods: Two hundred two children who satisfied criteria for surgery and were referred over a 10‐year period were studied. Children were divided into three surgical groups. Group 1 had both endoscopic sinus surgery and adenoidectomy, group 2 had endoscopic sinus surgery alone, and group 3 had adenoidectomy. After a follow‐up period of 12 months, improvement of symptoms was assessed.

Results: One hundred eighty‐three children had adequate follow‐up. Eighty seven percent of children in group 1 had improved symptoms, compared with 75% in group 2 and 52% in group 3 (P < .0001). Multivariate analysis showed that surgical procedure was a predictor of success. Asthma, smoke exposure, and age were independent predictors of success.

Conclusion: Children who fail medical therapy benefit from surgery. Following certain criteria, one can chose between adenoidectomy alone or endoscopic sinus surgery with adenoidectomy to optimize surgical treatment of these children.
Prognostic Factors in Well‐Differentiated Thyroid Carcinoma
Authors: Cushing Sharon L. , Palme Carsten E. , Audet Nathalie , Eski Spiro , Walfish Paul G. , Freeman Jeremy L.
Published: November 2004

Objectives: To test the prognostic significance of standard clinicopathologic factors in patients with well‐differentiated thyroid carcinoma (WDTC).

Study Design: A retrospective chart review of the thyroid cancer database at Mount Sinai Hospital (Toronto, Canada 1963–2000) was carried out.

Methods: All patients consecutively treated for WDTC with a follow‐up period of at least 5 years were eligible for inclusion. Relevant patient, tumor, treatment, and outcome data were collected. The main outcome measures were recurrence rate, actuarial overall, and disease‐specific survival at 20 years.

Results: Three hundred and thirty‐three patients (F 275, M 58) with a median age of 39.7 (range 9–82.9) years were eligible for inclusion in this study (median follow‐up 10.4 years, range 5–34.4 years, minimum 5 years). The recurrence rate was 15.6% (52 /333). The overall and disease‐specific survival at 10 years was 97.5% and 98.5%, respectively. Likewise, the overall and disease‐specific survival at 20 years was 88.4% and 93.3%, respectively. Clinicopathologic factors significant on multivariate regression for the development of disease recurrence included family history of WDTC, advanced stage, and total thyroidectomy (all P < .05). Similarly, advanced stage on presentation was associated with a worse disease‐specific survival on multivariate regression (all P < .05). There was a trend for age 60 or greater to predict disease‐specific survival (P = .09).

Conclusions: WDTC is associated with a significant recurrence rate but good disease‐specific survival. The most important prognostic factors are family history of WDTC, extent of surgical treatment (i.e., total thyroidectomy), and advanced initial stage of disease, with a trend for age 60 years and older.
Cochlear Implant Fixation Using Polypropylene Mesh and Titanium Screws
Authors: Davis Bryan M. , Labadie Robert F. , McMenomey Sean O. , Haynes David S.
Published: November 2004

Hypothesis: Fixation of cochlear implants using prosthetic mesh is an improvement of the traditional fixation methods.

Study Design: A retrospective chart review was performed examining all adult and pediatric patients between 1998 and 2003 who underwent cochlear implantation using polypropylene mesh and titanium screws to fix the cochlear implant internal receiver. Patient age at implantation, postoperative infections, device failures, device migrations or extrusions, cerebrospinal fluid (CSF) leaks, flap complications, epidural hematoma data, and follow‐up data were evaluated.

Results: Two hundred and eighty‐five patients were identified who received cochlear implantation using the polypropylene mesh securing technique. There were five postoperative infections, two device failures, zero flap complications, zero device migrations or extrusions, zero cerebral spinal fluid leaks, and zero epidural hematomas. The two delayed device failures in this series were not related to fixation technique.

Conclusions: We conclude that this technique is widely applicable, technically superior, and not associated with increased complications.
Pepsin and Carbonic Anhydrase Isoenzyme III as Diagnostic Markers for Laryngopharyngeal Reflux Disease
Authors: Johnston Nikki , Knight John , Dettmar Peter W. , Lively Mark O. , Koufman Jamie
Published: November 2004

Objectives/Hypothesis: The objective was to investigate the potential use of pepsin and carbonic anhydrase isoenzyme III (CA‐III) as diagnostic markers for laryngopharyngeal reflux disease.

Study Design: Prospective cell biological investigation was conducted of laryngeal biopsy specimens taken from 9 patients with laryngopharyngeal reflux disease and 12 normal control subjects using antibodies specific for human pepsin (produced in the authors' laboratory within the Department of Otolaryngology at Wake Forest University Health Sciences, Winston‐Salem, NC) and CA‐III.

Methods: Laryngeal biopsy specimens were frozen in liquid nitrogen for Western blot analysis and fixed in formalin for pepsin immunohistochemical study. Specimens between two groups (patients with laryngopharyngeal reflux disease and control subjects) were compared for the presence of pepsin. Further analyses investigated the correlation between pepsin, CA‐III depletion, and pH testing data.

Results: Analysis revealed that the level of pepsin was significantly different between the two groups (P < .001). Secondary analyses demonstrated that presence of pepsin correlated with CA‐III depletion in the laryngeal vocal fold and ventricle (P < .001) and with pH testing data in individuals with laryngopharyngeal reflux disease.

Conclusion: Pepsin was detected in 8 of 9 patients with laryngopharyngeal reflux disease, but not in normal control subjects (0 of 12). The presence of pepsin was associated with CA‐III depletion in the laryngeal vocal fold and ventricle. Given the correlation between laryngopharyngeal reflux disease and CA‐III depletion, it is highly plausible that CA‐III depletion, as a result of pepsin exposure during laryngopharyngeal reflux, predisposes laryngeal mucosa to reflux‐related inflammatory damage.
Auditory Brainstem Implantation in Patients with Neurofibromatosis Type 2
Authors: Kanowitz Seth J. , Shapiro William H. , Golfinos John G. , Cohen Noel L. , Roland J Thomas
Published: November 2004

Objectives: Multichannel auditory brainstem implants (ABI) are currently indicated for patients with neurofibromatosis type II (NF2) and schwannomas involving the internal auditory canal (IAC) or cerebellopontine angle (CPA), regardless of hearing loss (HL). The implant is usually placed in the lateral recess of the fourth ventricle at the time of tumor resection to stimulate the cochlear nucleus. This study aims to review the surgical and audiologic outcomes in 18 patients implanted by our Skull Base Surgery Team from 1994 through 2003.

Study Design: A retrospective chart review of 18 patients with ABIs.

Methods: We evaluated demographic data including age at implantation, number of tumor resections before implantation, tumor size, surgical approach, and postoperative surgical complications. The ABI auditory results at 1 year were then evaluated for number of functioning electrodes and channels, hours per day of use, nonauditory side effect profile and hearing results. Audiologic data including Monosyllable, Spondee, Trochee test (MTS) Word and Stress scores, Northwestern University Children's Perception of Speech (NU‐CHIPS), and auditory sensitivity are reported.

Results: No surgical complications caused by ABI implantation were revealed. A probe for lateral recess and cochlear nucleus localization was helpful in several patients. A range of auditory performance is reported, and two patients had no auditory perceptions. Electrode paddle migration occurred in two patients. Patient education and encouragement is very important to obtain maximum benefit.

Conclusions: ABIs are safe, do not increase surgical morbidity, and allow most patients to experience improved communication as well as access to environmental sounds. Nonauditory side effects can be minimized by selecting proper stimulation patterns. The ABI continues to be an emerging field for hearing rehabilitation in patients who are deafened by NF2.
Preoperative Ultrasound Is Worthwhile for Reoperative Parathyroid Surgery
Authors: Ghaheri Bobak A. , Koslin D Bradley , Wood Aaron H. , Cohen James I.
Published: November 2004

Objectives/Hypothesis: High‐resolution ultrasound and sestamibi scanning are regarded as the first‐line methods for preoperative localization of parathyroid adenomas. The utility of ultrasound in reoperative cases has been questioned because of concern that scarring will obscure normal tissue planes and vascularity that are critical to identification of an adenoma using this imaging modality. The purposes of the study were to evaluate the ability of high‐resolution ultrasound to accurately localize parathyroid adenomas in the reoperative exploration and to identify any factors that influence its accuracy

Study Design: Retrospective chart review at a tertiary care academic medical center.

Methods: All patients seen in referral for parathyroid surgery between May 1994 and September 2002 underwent high‐resolution ultrasound as their initial diagnostic test. Patients who subsequently underwent exploration were included in the study. Intraoperative and ultrasound findings were compared.

Results: One hundred forty‐two patients were included, 116 without and 26 with prior exploration. The sensitivity and positive predictive value of ultrasound were 86.9% and 89.1%, respectively. These data were not significantly different in patients without (88.2% and 90%) and in patients with (80% and 84.2%) prior thyroid or parathyroid surgery. The overall accuracy was 79% with a false‐negative rate of 11.3%. Thyroid nodularity was significantly more common (81.8%) in patients who had a false‐positive or false‐negative finding on ultrasound than in the total population (61.3%).

Conclusion: High‐resolution ultrasound is an accurate method for localizing parathyroid adenomas even in patients who have previously undergone parathyroid exploration. However, the presence of thyroid nodules can interfere with its accuracy.