bluuebunny/crossref_metadata_2025 huggingface dataset:
Dependence of electron density on Fermi energy in compensated n-type gallium antimonide
Authors: Bennett Herbert S. , Hung Howard , Heckert Alan
Published: November 2005

The majority electron density as a function of the Fermi energy is calculated in zinc blende, compensated n-type GaSb for donor densities between 1016 and 1019cm−3. The compensation acceptor density is 1016cm−3. These calculations solve the charge neutrality equation self-consistently for a four-band model (three conduction subbands at Γ, L, and X and one equivalent valence band at Γ) of GaSb. Our calculations assume parabolic densities of states and thus do not treat the density-of-states modifications due to high concentrations of dopants, many-body effects, and nonparabolicity of the bands. Even with these assumptions, the results are important for interpreting optical measurements such as Raman scattering measurements that are proposed as a nondestructive method for wafer acceptance tests.
Wave-solid interactions in laser-shock-induced deformation processes
Authors: Fan Y. , Wang Y. , Vukelic S. , Yao Y. L.
Published: November 2005

A model was developed for material deformation processes induced by laser-generated shock waves. The processes include laser peen forming (LPF) and laser shock peening (LSP) of metals. Numerical solutions of the model using finite element method were implemented in two steps: (1) explicit step, devoted to shock wave propagation, and (2) implicit step, calculating relaxation of material. A series of LPF and LSP experiments was conducted to validate the model. The residual stress measurements by synchrotron x-ray diffraction and deformation measurements by profilometry showed that the experimental and numerical results were in good agreement. It is the first time to numerically and experimentally study the novel process of micro-scale LPF. An important aspect of the work is that the numerical results were further analytically explored to gain improved understanding of wave-solid interaction including shock wave attenuation and shock velocity variation.
Printed thin-film transistors and complementary logic gates that use polymer-coated single-walled carbon nanotube networks
Authors: Hur Seung-Hyun , Kocabas Coskun , Gaur Anshu , Park O. Ok , Shim Moonsub , Rogers John A.
Published: November 2005

This paper reports on the electrical properties of thin-film transistors (TFTs) that use polymer-coated networks of single-walled carbon nanotubes (SWNTs) as the semiconductor with source and drain electrodes formed by high-resolution printing techniques. P-channel, n-channel, and ambipolar TFTs are demonstrated with bare SWNT networks, networks coated with polyethylene imine and with polyethylene oxide, respectively. Studies of the scaling of properties with channel length and tube density reveal important information about the operation of these devices. Complementary inverters made with n- and p-channel devices show gain larger than one and illustrate the potential use of these types of TFTs for complex logic circuits.
Hydrothermal waves in a liquid bridge with aspect ratio near the Rayleigh limit under microgravity
Authors: Schwabe D.
Published: November 2005

A 2 cSt silicone oil (Pr=28) liquid bridge of 15.0mm length L and 3.0mm radius r (aspect ratio A=L∕r=5) was established under microgravity during the flight of the sounding rocket MAXUS-4. Four different temperature differences ΔT=7, 9, 10, and 12K were applied between the ends, each for sufficient time to reach steady-state thermocapillary flow conditions. The aim of the experiment—to observe the onset of hydrothermal waves and to measure their features such as the wave phase speed and the angle between the wave vector and the applied temperature gradient—was reached. We used microgravity in this experiment in a twofold manner: (1) a liquid bridge with A=5 can be established only under microgravity; (2) it was possible to study hydrothermal waves without the influence of gravity and without the aspect ratio restrictions at normal gravity.
Field emission mechanism of oxidized highly phosphorus-doped homoepitaxial diamond (111)
Authors: Yamada Takatoshi , Nebel Christoph E. , Rezek Bohuslav , Takeuchi Daisuke , Fujimori Naoji , Namba Akihiko , Nishibayashi Yoshiki , Yamaguchi Hisato , Saito Ichitaro , Okano Ken
Published: November 2005

Spatially resolved electron field emission experiments on oxidized highly phosphorus-doped homoepitaxial diamond (111) were applied at room temperature. The diamond layer shows hopping conductivity. Field emission properties have three distinct regions. We attribute the variation in emission currents to: (a) Electron emission from conduction-band minimum (Region I), (b) Depletion of conduction-band electrons at the surface (Region II), and (c) emission from the phosphorus level (Region III). From these data, we calculate an effective positive electron affinity for the oxidized surface of 1–1.5eV.
Transition thresholds in the asymptotic suction boundary layer
Authors: Levin Ori , Davidsson E. Niklas , Henningson Dan S.
Published: November 2005

Energy thresholds for transition to turbulence in an asymptotic suction boundary layer is calculated by means of temporal direct numerical simulations. The temporal assumption limits the analysis to periodic disturbances with horizontal wave numbers determined by the computational box size. Three well known transition scenarios are investigated: oblique transition, the growth and breakdown of streaks triggered by streamwise vortices, and the development of random noise. Linear disturbance simulations and stability diagnostics are also performed for a base flow consisting of the suction boundary layer and a streak. The scenarios are found to trigger transition by similar mechanisms as obtained for other flows. Transition at the lowest initial energy is provided by the oblique wave scenario for the considered Reynolds numbers 500, 800, and 1200. The Reynolds number dependence on the energy thresholds are determined for each scenario. The threshold scales like Re−2.6 for oblique transition and like Re−2.1 for transition initiated by streamwise vortices and random noise, indicating that oblique transition has the lowest energy threshold also for larger Reynolds numbers.
Substitutional and interstitial oxygen in wurtzite GaN
Authors: Wright A. F.
Published: November 2005

Density-functional theory was used to compute energy-minimum configurations and formation energies of substitutional and interstitial oxygen (O) in wurtzite GaN. The results indicate that O substituted at a N site (ON) acts as a single donor with the ionized state (ON+1) being the most stable O state in p-type GaN. In n-type GaN, interstitial O (OI) is predicted to be a double acceptor and O substituted at a Ga site (OGa) is predicted to be a triple acceptor. The formation energies of these two species are comparable to that of ON in n-type GaN and, as such, they should form and compensate the ON donors. The extent of compensation was estimated for both Ga-rich and N-rich conditions with a total O concentration of 1017cm−3. Ga-rich conditions yielded negligible compensation and an ON concentration in excess of 9.9×1016cm−3. N-rich conditions yielded a 25% lower ON concentration, due to the increased stability of OI and OGa relative to ON, and moderate compensation. These findings are consistent with experimental results indicating that O acts as a donor in GaN(O). Complexes of ON with the Mg acceptor and OI with the Si donor were examined. Binding energies for charge-conserving reactions were ⩾0.5eV, indicating that these complexes can exist in equilibrium at room temperature. Complexes of ON with the Ga vacancy in n-type GaN were also examined and their binding energies were 1.2 and 1.4eV, indicating that appreciable concentrations can exist in equilibrium even at elevated temperatures.
Influence of composition diffusion on the band structures of InGaNAs∕GaAs quantum wells investigated by the band-anticrossing model
Authors: Qiu Y. N. , Rorison J. M. , Sun H. D. , Calvez S. , Dawson M. D. , Bryce A. C.
Published: November 2005

We investigate the influence of quantum-well intermixing (QWI) on the electronic band structure of GaInNAs∕GaAs multiquantum wells. The band structures and optical transitions have been calculated based on the band-anticrossing (BAC) model and Fick’s interdiffusion law for both intermixed and nonintermixed samples, respectively. The calculated results are consistent with the true optical transitions observed by photoluminescence excitation spectroscopy and secondary ion mass spectroscopy. Our investigation indicates that BAC model is valid for interdiffused quantum wells and verifies that the QWI process in GaInNAs∕GaAs multiquantum wells is induced mainly by the interdiffusion of In–Ga between the quantum wells and barriers.
Fe-encapsulated carbon nanotubes: Nanoelectromagnets
Authors: Su Yi-Chun , Hsu Wen-Kuang
Published: November 2005

Existence of chiral current in carbon nanotubes is verified by the presence of inductive phase. The magnetic strength at the center of nanotubes can be magnified by encapsulation of Fe.
Optimizing the superlens: Manipulating geometry to enhance the resolution
Authors: Podolskiy Viktor A. , Kuhta Nicholas A. , Milton Graeme W.
Published: November 2005

We analyze the performance of a planar lens based on realistic negative index material in a generalized geometry. We demonstrate that the conventional superlens design (where the lens is centered between the object and the image) is not optimal from the resolution point of view, develop an analytical expression for the resolution limit of a generalized lens, use it to find the optimum lens configuration, and calculate the maximum absorption practical nearfield superlenses may have. We demonstrate that in contrast to the conventional superlens picture, planar imaging is typically accompanied by excitation of surface waves at both interfaces of the lens.
Low-loss quasi-planar ridge waveguides formed on thin silicon-on-insulator
Authors: Webster M. A. , Pafchek R. M. , Sukumaran G. , Koch T. L.
Published: November 2005

Low-loss, quasi-planar ridge waveguide structures have been designed and fabricated in silicon-on-insulator material with waveguide propagation losses of <0.7dB∕cm at 1550nm, and a Q∼106 measured in a ring resonator configuration. These structures offer tight vertical field confinement with scalable bending losses, and should be of interest for integration with both active and passive components. Waveguides were fabricated using optical lithography and processing compatible with silicon electronics.
Ultrahigh speed germanium-on-silicon-on-insulator photodetectors for 1.31 and 1.55μm operation
Authors: Rouvière M. , Vivien L. , Le Roux X. , Mangeney J. , Crozat P. , Hoarau C. , Cassan E. , Pascal D. , Laval S. , Fédéli J.-M. , Damlencourt J.-F. , Hartmann J. M. , Kolev S.
Published: November 2005

We report the fabrication and the characterization of interdigited metal-germanium on silicon metal photodetectors (metal-semiconductor-metal or MSM) for operation at both optical telecommunication wavelengths: 1.31 and 1.55μm. Femtosecond impulse and frequency experiments have been carried out to characterize those MSM Ge photodetectors. For both wavelengths, the measured 3dB bandwidth under 2V bias are close to 10, 18, 20, and 35GHz for electrode spacings equal to 2000, 1000, 700, and 500nm, respectively.
Synthesis and ethanol sensing characteristics of single crystalline SnO2 nanorods
Authors: Chen Y. J. , Xue X. Y. , Wang Y. G. , Wang T. H.
Published: November 2005

In a basic water-alcohol mixing solution without any other toxically organic solvents, the single crystalline SnO2 nanorods with diameters of 4–15 nm and lengths of 100–200 nm were synthesized using SnCl4 as a precursor. The sensors fabricated from the nanorods exhibited the sensitivity of 31.4 for 300 ppm of ethanol. Both the response and recovery time are short, around 1 s. Moreover, a linear dependence of the sensitivity on the ethanol concentration was observed. These behaviors were well explained by considering the high surface-to-volume ratio of the nanorods.
All-optical switching of defect mode in two-dimensional nonlinear organic photonic crystals
Authors: Hu Xiaoyong , Gong Qihuang , Liu Yuanhao , Cheng Bingying , Zhang Daozhong
Published: November 2005

An all-optical switching is demonstrated by use of defect mode in two-dimensional nonlinear photonic crystals made of polystyrene. Transmittance contrast of about 70% is achieved for the probe light. The dynamical shifts of the defect mode induced by pump intensity are measured and analyzed in detail. It is found that the defect mode shifts 5 nm under the excitation of 18.7GW∕cm2 pump intensity, which is in agreement with the theoretical predictions. Time response of the optical switching is smaller than the laser pulse of about 10 ps.
Quantum and transport lifetimes of two-dimensional electrons gas in AlGaN∕GaN heterostructures
Authors: Lorenzini P. , Bougrioua Z. , Tiberj A. , Tauk R. , Azize M. , Sakowicz M. , Karpierz K. , Knap W.
Published: November 2005

The transport and quantum lifetimes were respectively deduced from low-temperature mobility and Shubnikov–de Haas measurements as a function of carrier density in metal organic vapor phase epitaxy-grown AlGaN∕GaN∕sapphire heterostructures. We show experimentally that the lifetime ratio varies as a bell curve, qualitatively confirming a recent theoretical prediction. However the experimental ratio varied much less than was theoretically predicted: From 9 to 19 for carrier densities in 1–9×1012cm−2 range. Moreover, we show the variation of quantum time with carrier density presents some discrepancy with the theoretical study. We also show that transport to quantum lifetime ratio cannot be used alone as a clear figure of merit from AlGaN∕GaN heterojunctions.
Mutation in sodium–calcium exchanger 1 (NCX1) causes cardiac fibrillation in zebrafish
Authors: Langenbacher Adam D. , Dong Yuan , Shu Xiaodong , Choi Jayoung , Nicoll Debora A. , Goldhaber Joshua I. , Philipson Kenneth D. , Chen Jau-Nian
Published: November 2005

Cardiac fibrillation, a form of cardiac arrhythmia, is the most common cause of embolic stroke and death associated with heart failure. The molecular mechanisms underlying cardiac fibrillation are largely unknown. Here we report a zebrafish model for cardiac fibrillation. The hearts of zebrafishtremblor(tre) mutants exhibit chaotic movements and fail to develop synchronized contractions. Calcium imaging showed that normal calcium transients are absent intrecardiomyocytes, and molecular cloning of thetremutation revealed that thetrelocus encodes the zebrafish cardiac-specific sodium–calcium exchanger (NCX) 1, NCX1h. Forced expression of NCX1h or other calcium-handling molecules restored synchronized heartbeats intremutant embryos in a dosage-dependent manner, demonstrating the critical role of calcium homeostasis in maintaining embryonic cardiac function. By creating mosaic zebrafish embryos, we showed that sporadic NCX1h-null cells were not sufficient to disrupt normal cardiac function, but clustered wild-type cardiomyocytes contract in unison intremutant hearts. These data signify the essential role of calcium homeostasis and NCX1h in establishing rhythmic contraction in the embryonic zebrafish heart.
Counting human somatic cell replications: Methylation mirrors endometrial stem cell divisions
Authors: Kim Jung Yeon , Tavaré Simon , Shibata Darryl
Published: November 2005

Cell proliferation may be altered in many diseases, but it is uncertain exactly how to measure total numbers of divisions. Although it is impossible to count every division directly, potentially total numbers of stem cell divisions since birth may be inferred from numbers of somatic errors. The idea is that divisions are surreptitiously recorded by random errors that occur during replication. To test this “molecular clock” hypothesis, epigenetic errors encoded in certain methylation patterns were counted in glands from 30 uteri. Endometrial divisions can differ among women because of differences in estrogen exposures or numbers of menstrual cycles. Consistent with an association between mitotic age and methylation, there was an age-related increase in methylation with stable levels after menopause, and significantly less methylation was observed in lean or older multiparous women. Methylation patterns were diverse and more consistent with niche rather than immortal stem cell lineages. There was no evidence for decreased stem cell survival with aging. An ability to count lifetime numbers of stem cell divisions covertly recorded by random replication errors provides new opportunities to link cell proliferation with aging and cancer.
Loss of dispensable genes is not adaptive in yeast
Authors: Sliwa Piotr , Korona Ryszard
Published: November 2005

A substantial share of genes identified in yeast can be deleted without visible phenotypic effects. Current debate concentrates on the possible roles of seemingly dispensable genes. The costs of maintaining unnecessary functions has attracted little attention. The hypothesis of antagonistic pleiotropy postulates that adaptations to different constituents of the environment are likely to interfere with each other, and therefore loss of unnecessary functions is potentially advantageous. We tested an entire collection of nonessential yeast gene deletions in a benign and nutritionally rich environment in which the number of dispensable genes was particularly high. We applied a series of competition experiments that could detect differences in relative fitness of ≈0.005. No beneficial deletions were found, except perhaps for the deletion of about a dozen genes that slightly improved competitive ability; however, a functional explanation of the fitness advantage is lacking. The paucity of beneficial gene deletions is striking because genetic adaptations to laboratory conditions are regularly observed in yeast. However, it accords with the finding that the gene contents of four species ofSaccharomycesare nearly identical, despite up to 20 million years of independent evolution and extensive DNA sequence divergence. Such extreme conservation of functions would be improbable if there were periods of selection promoting the loss of temporarily dispensable genes. The evident cohesion of the yeast genomes may be their evolved feature or an intrinsic property of complex genetic systems.
KCNQ1-dependent transport in renal and gastrointestinal epithelia
Authors: Vallon Volker , Grahammer Florian , Volkl Harald , Sandu Ciprian D. , Richter Kerstin , Rexhepaj Rexhepi , Gerlach Uwe , Rong Qi , Pfeifer Karl , Lang Florian
Published: November 2005

Mutations in the gene encoding for the K
+
channel α-subunit KCNQ1 have been associated with long QT syndrome and deafness. Besides heart and inner ear epithelial cells, KCNQ1 is expressed in a variety of epithelial cells including renal proximal tubule and gastrointestinal tract epithelial cells. At these sites, cellular K
+
ions exit through KCNQ1 channel complexes, which may serve to recycle K
+
or to maintain cell membrane potential and thus the driving force for electrogenic transepithelial transport, e.g., Na
+
/glucose cotransport. Employing pharmacologic inhibition and gene knockout, the present study demonstrates the importance of KCNQ1 K
+
channel complexes for the maintenance of the driving force for proximal tubular and intestinal Na
+
absorption, gastric acid secretion, and cAMP-induced jejunal Cl
-
secretion. In the kidney, KCNQ1 appears dispensable under basal conditions because of limited substrate delivery for electrogenic Na
+
reabsorption to KCNQ1-expressing mid to late proximal tubule. During conditions of increased substrate load, however, luminal KCNQ1 serves to repolarize the proximal tubule and stabilize the driving force for Na
+
reabsorption. In mice lacking functional KCNQ1, impaired intestinal absorption is associated with reduced serum vitamin B12 concentrations, mild macrocytic anemia, and fecal loss of Na
+
and K
+
, the latter affecting K
+
homeostasis.
Solution structure of the Set2–Rpb1 interacting domain of human Set2 and its interaction with the hyperphosphorylated C-terminal domain of Rpb1
Authors: Li Ming , Phatnani Hemali P. , Guan Ziqiang , Sage Harvey , Greenleaf Arno L. , Zhou Pei
Published: November 2005

The phosphorylation state of the C-terminal repeat domain (CTD) of the largest subunit of RNA polymerase II changes as polymerase transcribes a gene, and the distinct forms of the phospho-CTD (PCTD) recruit different nuclear factors to elongating polymerase. The Set2 histone methyltransferase from yeast was recently shown to bind the PCTD of elongating RNA polymerase II by means of a novel domain termed the Set2–Rpb1 interacting (SRI) domain. Here, we report the solution structure of the SRI domain in human Set2 (hSRI domain), which adopts a left-turned three-helix bundle distinctly different from other structurally characterized PCTD-interacting domains. NMR titration experiments mapped the binding surface of the hSRI domain to helices 1 and 2, and Biacore binding studies showed that the domain binds preferably to [Ser-2 + Ser-5]-phosphorylated CTD peptides containing two or more heptad repeats. Point-mutagenesis studies identified five residues critical for PCTD binding. In view of the differential effects of these point mutations on binding to different CTD phosphopeptides, we propose a model for the hSRI domain interaction with the PCTD.
Bioinformatic analyses implicate the collaborating meiotic crossover/chiasma proteins Zip2, Zip3, and Spo22/Zip4 in ubiquitin labeling
Authors: Perry Jason , Kleckner Nancy , Börner G. Valentin
Published: November 2005

Zip2 and Zip3 are meiosis-specific proteins that, in collaboration with several partners, act at the sites of crossover-designated, axis-associated recombinational interactions to mediate crossover/chiasma formation. Here, Spo22 (also called Zip4) is identified as a probable functional collaborator of Zip2/3. The molecular roles of Zip2, Zip3, and Spo22/Zip4 are unknown. All three proteins are part of a small evolutionary cohort comprising similar homologs in four related yeasts. Zip3 is shown to contain a RING finger whose structural features most closely match those of known ubiquitin E3s. Further, Zip3 exhibits major domainal homologies to Rad18, a known DNA-binding ubiquitin E3. Also described is an approach to the identification and mapping of repeated protein sequence motifs, Alignment Based Repeat Annotation (ABRA), that we have developed. When ABRA is applied to Zip2 and Spo22/Zip4, they emerge as a 14-blade WD40-like repeat protein and a 22-unit tetratricopeptide repeat protein, respectively. WD40 repeats of Cdc20, Cdh1, and Cdc16 and tetratricopeptide repeats of Cdc16, Cdc23, and Cdc27, all components of the anaphase-promoting complex, are also analyzed. These and other findings suggest that Zip2, Zip3, and Zip4 act together to mediate a process that involves Zip3-mediated ubiquitin labeling, potentially as a unique type of ubiquitin-conjugating complex.
Retrograde signaling from the brain to the retina modulates the termination of the light response in
Drosophila
Authors: Rajaram Shantadurga , Scott Robert L. , Nash Howard A.
Published: November 2005

A critical factor in visual function is the speed with which photoreceptors (PRs) return to the resting state when light intensity dims. Several elements subserve this process, many of which promote the termination of the phototransduction cascade. Although the known elements are intrinsic to PRs, we have found that prompt restoration to the resting state of the
Drosophila
electroretinogram can require effective communication between the retina and the underlying brain. The requirement is seen more dramatically with long than with short light pulses, distinguishing the phenomenon from gross disruption of the termination machinery. The speed of recovery is affected by mutations (in the
Hdc
and
ort
genes) that prevent PRs from transmitting visual information to the brain. It is also affected by manipulation (using either drugs like neostigmine or genetic tools to inactivate neurotransmitter release) of cholinergic signals that arise in the brain. Intracellular recordings support the hypothesis that PRs are the target of this communication. We infer that signaling from the retina to the optic lobe prompts a feedback signal to retinal PRs. Although the mechanism of this retrograde signaling remains to be discerned, the phenomenon establishes a previously unappreciated mode of control of the temporal responsiveness of a primary sensory neuron.
Global gene expression profiles reveal significant nuclear reprogramming by the blastocyst stage after cloning
Authors: Smith Sadie L. , Everts Robin E. , Tian X. Cindy , Du Fuliang , Sung Li-Ying , Rodriguez-Zas Sandra L. , Jeong Byeong-Seon , Renard Jean-Paul , Lewin Harris A. , Yang Xiangzhong
Published: November 2005

Nuclear transfer (NT) has potential applications in agriculture and biomedicine, but the technology is hindered by low efficiency. Global gene expression analysis of clones is important for the comprehensive study of nuclear reprogramming. Here, we compared global gene expression profiles of individual bovine NT blastocysts with their somatic donor cells and fertilized control embryos using cDNA microarray technology. The NT embryos' gene expression profiles were drastically different from those of their donor cells and closely resembled those of the naturally fertilized embryos. Our findings demonstrate that the NT embryos have undergone significant nuclear reprogramming by the blastocyst stage; however, problems may occur during redifferentiation for tissue genesis and organogenesis, and small reprogramming errors may be magnified downstream in development.
Dpp signaling and the induction of neoplastic tumors by caspase-inhibited apoptotic cells in
Drosophila
Authors: Pérez-Garijo Ainhoa , Martín Francisco A. , Struhl Gary , Morata Ginés
Published: November 2005

In
Drosophila
, stresses such as x-irradiation or severe heat shock can cause most epidermal cells to die by apoptosis. Yet, the remaining cells recover from such assaults and form normal adult structures, indicating that they undergo extra growth to replace the lost cells. Recent studies of cells in which the cell death pathway is blocked by expression of the caspase inhibitor P35 have raised the possibility that dying cells normally regulate this compensatory growth by serving as transient sources of mitogenic signals. Caspase-inhibited cells that initiate apoptosis do not die. Instead, they persist in an “undead” state in which they ectopically express the signaling genes
decapentaplegic
(
dpp
) and
wingless
(
wg
) and induce abnormal growth and proliferation of surrounding tissue. Here, using mutations to abolish Dpp and/or Wg signaling by such undead cells, we show that Dpp and Wg constitute opposing stimulatory and inhibitory signals that regulate this excess growth and proliferation. Strikingly, we also found that, when Wg signaling is blocked, unfettered Dpp signaling by undead cells transforms their neighbors into neoplastic tumors, provided that caspase activity is also blocked in the responding cells. This phenomenon may provide a paradigm for the formation of neoplastic tumors in mammalian tissues that are defective in executing the cell death pathway. Specifically, we suggest that stress events (exposure to chemical mutagens, viral infection, or irradiation) that initiate apoptosis in such tissues generate undead cells, and that imbalances in growth regulatory signals sent by these cells can induce the oncogenic transformation of neighboring cells.
Removing intensity effects and identifying significant genes for Affymetrix arrays in macrophage migration inhibitory factor-suppressed neuroblastoma cells
Authors: Fan Jianqing , Chen Yongxiong , Chan Hiu Man , Tam Paul K. H. , Ren Yi
Published: November 2005

A semilinear in-slide model is introduced to remove the intensity effect in the scanning process. It is demonstrated that the intensity effect can be estimated accurately and removed effectively. This normalization step is vital for Affymetrix arrays to reveal relevant biological results when comparing gene expression in multiple arrays. The normalized expression ratios are analyzed further by a modified two-samplettest along with a sieved permutation scheme for computingPvalues. The improved specificity and sensitivity are demonstrated by using a study on the impact of macrophage migration inhibitory factor (MIF) reduction in neuroblastoma cells. With semilinear in-slide model analysis, expression of 166 genes was altered with aPvalue no greater than 0.001. Among those genes, 44 were altered >2-fold. MIF-regulated genes associated with tumor development including IL-8 andC-met, which are overexpressed in many tumors, were down-regulated in MIF-reduced cells. On the other hand, some tumor-suppressor genes such asEPHB6, visinin-like protein 1 (VSNL-1), andBLUwere up-regulated in MIF-reduced cells. In addition, we demonstrated that down-regulation of MIF expression could result in a reduction in cell proliferation and tumor growthin vitroandin vivo. Our data not only demonstrate that targeting MIF expression is a promising therapeutic strategy in human neuroblastoma therapy but also indicate the MIF target genes for additional study.
Lack of Urinary Bladder Carcinogenicity of Sodium L-Ascorbate in Human c-Ha-ras Proto-Oncogene Transgenic Rats
Authors: Morimura Keiichirou , Kang Jin Seok , Wei Min , Wanibuchi Hideki , Tsuda Hiroyuki , Fukushima Shoji
Published: November 2005

Sodium L-ascorbate (Na-AsA) is widely known to be a tumor promoter of rat bladder carcinogenesis but tests negative in standard 2-year bioassays. In the present study, bladder-cancer-susceptible transgenic rats designated Hras128 were used to further examine the tumorigenicity of Na-AsA. A total of 40 7-week-old male transgenic (Tg) and 42 littermate nontransgenic (Non-tg) rats were divided into 4 groups and given powdered MF diet with or without 5% Na-AsA for 57 weeks. Tg rats showed significantly short survival compared with Non-tg, independent of Na-AsA treatment. Tg rats treated with Na-AsA showed a slightly higher incidence of carcinoma (29.6%) as compared to those without Na-AsA treatment (15.4%), but this was without statistical significance. Moreover, the total bladder tumor incidences, including papillomas, did not differ statistically (with Na-AsA, 37.0%; without Na-AsA, 30.8%). No bladder tumor was detected in Non-tg rats. Various kinds of other lesions in various organs were noted in Tg rats treated with or without Na-AsA treatment, but no intergroup differences were evident. In conclusion, Na-AsA did not show tumorigenicity in highly bladder-cancer-susceptible transgenic Hras128 rats. These results suggest that Na-AsA is a pure promoter but not a complete carcinogen in rats.
Institutional Breakdown? An Exploratory Taxonomy of Australian University Failure
1
Authors: Murray David , Dollery Brian
Published: November 2005

Australian higher education has undergone radical change aimed at transforming universities into commercial enterprises less dependent on public funding. Despite some significant successes, including dramatic increases in the numbers of domestic and international students, decreased Commonwealth subsidies, and more private sector finance, there are ominous indications that institutional failure is endemic, especially financial accountability. Drawing on various theories of institutional failure, this paper attempts to examine the causes of the current crisis. A fourfold taxonomy of Australian university failure is developed that identifies governance failure, accountability failure, quality failure, and information failure as the primary sources of tertiary education institutional breakdown.
Making Sense of Organizational Failure: The Marconi Debacle
Authors: Kam Jacqueline
Published: November 2005

Organizational failure is usually explained with linear causality, attributed to either environmental change or managerial behavior. This paper attempts to capture the dynamic interplays of human actions in changing environments, taking into account both the environmental and behavioral factors. The breath‐taking debacle of Marconi, a British telecommunications equipment supplier, is examined, revealing the complexities and interrelatedness of the environmental change and human actions, and the consequences for organizational performance. This research is intended to develop thinking about organizational failure, to broaden perspectives currently framed by conventional boundaries, and to encourage a new approach in making sense of failure. Failure may seem obvious and its understanding simple; in fact, failure is an elusive concept and the simplicity commonly attached to its understanding is dangerously deceptive.
Global Landscapes: A Speculative Assessment of Emerging Organizational Structures within the International Wine Industry
Authors: Aylward David
Published: November 2005

As a rapidly evolving sector the international wine industry represents an interesting subject for analysis. Over the past two centuries the industry has experienced a number of major innovations and direction changes. The organizational shifts involved in these changes have been profound. From a monopolization of wine culture through the nineteenth and much of the twentieth century by Europeans, to the emergence of New World operators and their democratic influence, the international wine industry now stands at the edge of another major paradigm shift. This paper traces the industry’s historical changes and speculates on the implications of such issues as global production, distribution, technology transfer, branding and the escalation of mergers and alliances. It argues that with the increasing global tendency of the industry, ‘New’ and ‘Old World’ distinctions may blur and disappear. Furthermore, as the wine landscape continues to evolve, we may well see a new set of rules, where the emergence of localized branding, an enhanced role for small to medium enterprises and the decline of national industries results in an irrevocable reconfiguration of the industry.
No significant effect of acute moderate alcohol intake on leptin levels in healthy male volunteers
Authors: Dammann Gerhard , Dierkes Jutta , Graf Marc , Wiesbeck Gerhard , Pridzun Lutz , Schulte Tilman , Westphal Sabine , Luley Claus , Allen John , Wurst Friedrich
Published: November 2005

As, for ethical reasons, it is difficult to investigate by an experiment the effect of acute intoxication on leptin levels in alcoholics, we tested the hypothesis of lowered levels as an effect of acute ethanol intake in healthy volunteers. The subjects comprised (1) 17 healthy male participants, recruited via newspaper advertisements [age 29?3.75 years, body mass index (BMI) 24.3?3.5, leptin at baseline 3.3?3.1ng/ml]; (2) for comparison, leptin levels of 16 male alcoholic patients at day 1 of withdrawal were used. They were characterized as follows: (mean, median, standard deviation and range) age in years (41.1, 40.5, 10.2, 24, 57), BMI (23.3, 21.7, 5.4, 16.6, 37.5), 1032g of ethanol (median) consumed within the last 7 days, leptin levels 2.3mg/ml. A placebo‐controlled double‐blind trial was performed. Leptin levels of blood samples were taken at baseline (t1), before ethanol intake (t2), when blood alcohol had reached its maximum (t3) and the morning after (t4). The oral dose of ethanol administered was 0.6g/kg ethanol. (1) Volunteers: (a) the ethanol and placebo group exhibited leptin levels corresponding closely with levels measured at baseline (t1) (rs=0.85, p <0.0001) and follow‐up (t4) (rs=0.768, p<0.0001). (b) Leptin levels for the placebo and the alcohol‐consuming (verum) group did not differ significantly at baseline, after ethanol intake or on the morning after [Mann‐Whitney U‐test (p=0.669, p=1.0 and p=0.887, respectively)]. (2) Leptin levels in relation to BMI did not significantly differ at any measurement time in either group. (3) Leptin levels/BMI of the healthy volunteers at t1 and t4 were not significantly different from those of 16 alcoholics. The data do not support the hypothesis of a significant effect of acute moderate alcohol intake on leptin levels in healthy volunteers.
Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism?
Authors: Egli Mark
Published: November 2005

Evaluating medications in animal laboratory paradigms can reveal whether the compound is effective in an established alcoholism model, at clinically relevant doses and exposure conditions, when administered orally (or transdermally) and without serious limiting side effects. Positive outcomes constitute a possible discovery for relevance to alcoholism and, under favorable marketing conditions, encourage further development. Medication testing using animal models of alcoholism might also guide clinical testing by discriminating clinically effective from clinically ineffective compounds. This ability rests on whether there are tests or, more reasonably, batteries of tests having this discriminative ability. The present paper examines this possibility. Effects of naltrexone and acamprosate in animal paradigms which model behavioral aspects of alcoholism are reviewed and compared with the effects of compounds which have limited effects in alcoholics. It is not clear at present whether any single paradigm or combination of paradigms differentiates clinically effective from clinically limited compounds. Steps are suggested to improve the use of preclinical laboratory tests to predict which compounds are likely to be effective medications for reducing drinking and sustaining abstinence in human alcoholics.
Methylone and mCPP, two new drugs of abuse?
Authors: Bossong M. , Van Dijk J. , Niesink R.
Published: November 2005

Recently, two new ecstasy‐like substances, methylone and mCPP, were found in street drugs in the Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4‐methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared on the Dutch drug market, called ‘Explosion’. mCPP (meta‐chlorophenylpiperazine) is a substance often used as a probe for the serotonin function in psychiatric research, and has now been found in street drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems, resembling MDMA (3,4‐methylenedioxymethamphetamine), with mCPP mainly affecting the serotonin system. The subjective effects of both new substances exhibit subtle differences with those of MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because of similarities between these substances and MDMA, risks common to MDMA cannot be excluded.
Enhanced prolactin levels in opium smokers
Authors: Moshtaghi‐Kashanian Ghollam‐Reza , Esmaeeli Farzaneh , Dabiri Shahriar
Published: November 2005

In Iran, opium is smoked for pleasure or as a medication by some people. It is a complex mixture of 40 different alkaloids, including morphine and codeine along with many impurities. Although it is well established that opioids or tobacco affect many physiological functions in humans, to our knowledge there has been no specific study looking at these effects in opium smokers. To assess that, we investigated the circulating levels of prolactin, TSH, LH, FSH and testosterone in male opium smokers who also smoke cigarettes (n =23, aged 28.4?4.1 years), and comparing this with the corresponding values for nicotine abusers (n =12, 15–25 cigarettes/day) or a healthy control group (n =20) of the same age. Our results showed that 86.96% of the opium‐dependent and 41.67 % of the nicotine‐dependent group displayed high prolactin values (p)
Opioid plasma concentrations in methadone‐and buprenorphine‐maintained patients
Authors: Jagsch Reinhold , Gombas Wolfgang , Schindler Shird‐Dieter , Eder Harald , Moody David , Fischer Gabriele
Published: November 2005

This is the first trial to compare the relationship of opioid plasma concentrations in methadone‐versus buprenorphine‐maintained subjects. Sixty subjects (19 females and 41 males) seeking treatment who met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for opioid dependence were recruited and treated at the Drug Addiction Outpatient Clinic at the University of Vienna. Of these, 44 (11 female and 33 male) were included in the analyses of plasma concentrations. Subjects received either daily sublingual buprenorphine (2mg or 8mg tablets; maximum daily dose: 8mg) or oral methadone (racemic R‐/S‐methadone) and were maintained on a stable dose after an induction period of 2 weeks. Mean dose and mean plasma concentrations were correlated on an individual and collective basis. Correlation was 0.51 for buprenorphine, whereas the score for methadone was 0.69. Intra‐individual variation was much higher for buprenorphine (p < 0.0001), while the concentration‐to‐dose ratio was very small. Based on the differences of the pharmacokinetics of blood plasma of the two agents, we tried to explain the differences in the acceptance of treatment, which was significantly lower in the buprenorphine‐maintained group. No such differences could be evaluated between completers and dropouts in buprenorphine‐maintained subjects, neither concerning withdrawal scores nor dose, plasma concentration, concentration‐to‐dose ratios or intra‐individual variation.
RanBP3 enhances nuclear export of active β-catenin independently of CRM1
Authors: Hendriksen Jolita , Fagotto Francois , van der Velde Hella , van Schie Martijn , Noordermeer Jasprien , Fornerod Maarten
Published: November 2005

β-Catenin is the nuclear effector of the Wnt signaling cascade. The mechanism by which nuclear activity of β-catenin is regulated is not well defined. Therefore, we used the nuclear marker RanGTP to screen for novel nuclear β-catenin binding proteins. We identified a cofactor of chromosome region maintenance 1 (CRM1)–mediated nuclear export, Ran binding protein 3 (RanBP3), as a novel β-catenin–interacting protein that binds directly to β-catenin in a RanGTP-stimulated manner. RanBP3 inhibits β-catenin–mediated transcriptional activation in both Wnt1- and β-catenin–stimulated human cells. In Xenopus laevis embryos, RanBP3 interferes with β-catenin–induced dorsoventral axis formation. Furthermore, RanBP3 depletion stimulates the Wnt pathway in both human cells and Drosophila melanogaster embryos. In human cells, this is accompanied by an increase of dephosphorylated β-catenin in the nucleus. Conversely, overexpression of RanBP3 leads to a shift of active β-catenin toward the cytoplasm. Modulation of β-catenin activity and localization by RanBP3 is independent of adenomatous polyposis coli protein and CRM1. We conclude that RanBP3 is a direct export enhancer for β-catenin, independent of its role as a CRM1-associated nuclear export cofactor.
Mutants in trs120 disrupt traffic from the early endosome to the late Golgi
Authors: Cai Huaqing , Zhang Yueyi , Pypaert Marc , Walker Lee , Ferro-Novick Susan
Published: November 2005

Transport protein particle (TRAPP), a large complex that mediates membrane traffic, is found in two forms (TRAPPI and -II). Both complexes share seven subunits, whereas three subunits (Trs130p, -120p, and -65p) are specific to TRAPPII. Previous studies have shown that mutations in the TRAPPII-specific gene trs130 block traffic through or from the Golgi. Surprisingly, we report that mutations in trs120 do not block general secretion. Instead, trs120 mutants accumulate aberrant membrane structures that resemble Berkeley bodies and disrupt the traffic of proteins that recycle through the early endosome. Mutants defective in recycling also display a defect in the localization of coat protein I (COPI) subunits, implying that Trs120p may participate in a COPI-dependent trafficking step on the early endosomal pathway. Furthermore, we demonstrate that Trs120p largely colocalizes with the late Golgi marker Sec7p. Our findings imply that Trs120p is required for vesicle traffic from the early endosome to the late Golgi.
Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection
Authors: Routes John M. , Ryan Sharon , Morris Kristin , Takaki Rayna , Cerwenka Adelheid , Lanier Lewis L.
Published: November 2005

The expression of the Adenovirus serotype 5 (Ad5) E1A oncogene sensitizes tumor cells to natural killer (NK) cell–mediated killing and tumor rejection in vivo. These effects are dependent on the ability of E1A to bind the transcriptional coadaptor protein p300. To test the hypothesis that E1A up-regulates ligands recognized by the NKG2D-activating receptor, we stably transfected the highly tumorigenic mouse fibrosarcoma cell line MCA-205 with Ad5-E1A or a mutant form of E1A that does not interact with p300 (E1A-Δp300). Ad5-E1A, but not E1A-Δp300, up-regulated the expression of the NKG2D ligand retinoic acid early inducible (RAE)-1, but not murine ULBP-like transcript 1, another NKG2D ligand, in four independently derived MCA-205 transfectants. The up-regulation of RAE-1 by E1A targeted MCA-205 tumor cells to lysis by NK cells, resulting in NKG2D-dependent tumor rejection in vivo. Moreover, the up-regulation of NKG2D ligands by E1A was not limited to mouse tumor cells, as E1A also increased the expression of NKG2D ligands on primary baby mouse kidney cells, human MB435S breast cancer cells, and human H4 fibrosarcoma cells.
Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction
Authors: Hessel Edith M. , Chu Mabel , Lizcano Jennifer O. , Chang Bonnie , Herman Nancy , Kell Sariah A. , Wills-Karp Marsha , Coffman Robert L.
Published: November 2005

A single treatment with a CpG-containing immunostimulatory DNA sequence (ISS) given before allergen challenge can inhibit T helper type 2 cell (Th2)–mediated airway responses in animal models of allergic asthma; however, the mechanism of this inhibition remains largely undefined. Here, we demonstrate that airway delivery of ISS before allergen challenge in Th2-primed mice acts in two distinct ways to prevent the allergic responses to this challenge. The first is to prevent induction of cytokines from allergen-specific Th2 cells, as demonstrated by the nearly complete inhibition of Th2 cytokine production, Th2-dependent functional responses, and gene induction patterns. ISS inhibits the Th2 response by rendering lung antigen-presenting cells (APCs) unable to effectively present antigen to Th2 cells, but not to Th1 cells. This loss of APC function correlates with a reduced expression of costimulatory molecules, including programmed cell death ligand (PD-L)1, PD-L2, CD40, CD80, CD86, and inducible T cell costimulator, and of major histocompatibility complex class II on CD11c+APCs from the airways of ISS-treated mice. The second important action of ISS is inhibition of immunoglobulin E–dependent release of Th2 cytokines, especially interleukin 4, from basophils and/or mast cells in the airways of Th2-primed mice. Thus, inhibition by ISS of allergic responses can be explained by two novel mechanisms that culminate in the inhibition of the principal sources of type 2 cytokines in the airways.