bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic Structures of Quantum Well of A1-xBx Alloy Semiconductor in Coherent Potential Approximation
Authors: Shinozuka Yuzo
Published: November 2006

The electronic structures of a quantum well constructed from the binary alloy semiconductor A1-x
B
x
are studied by coherent potential approximation (CPA). A tight binding model is used for a single particle (electron, hole, or Frenkel exciton) in a well composed of a rectangular array of N

x
×N

y
×N

z
sites. The effects of diagonal randomness are included as the coherent potential Σ(E), which is assumed to be the same for all sites, and is self-consistently determined with the average Green's function. For slab (∞,∞,N

z
) and wire (∞,N

y
,N

z
) structures, the energy density of states ρ(E) is composed of N

z
(or N

y
×N

z
) subbands with the remains of a two (one)-dimensional van-Hove singularity. When x (or 1-x) is small, a B (A) impurity band always appears on the lower (higher) energy side of the lowest (highest) host subband. The metamorphosis of ρ(E) and the absorption spectrum I(E) due to the creation of a Frenkel exciton by changing the well size and the dimensionality is extensively discussed.
Thermoelectric Properties of Doped Half-Heuslers NbCoSn1-xSbx and Nb0.99Ti0.01CoSn1-xSbx
Authors: Ono Yasuhiro , Inayama Shingo , Adachi Hideaki , Kajitani Tsuyoshi
Published: November 2006

The thermoelectric properties of doped half-Heuslers, NbCoSn1-x
Sb
x
and Nb0.99Ti0.01CoSn1-x
Sb
x
, have been studied in the temperature range from 320 to 850 K. These half-Heuslers are synthesized by the arc melting of pure metals followed by annealing for one week at 1123 K in vacuum. The samples with x=0, 0.02, 0.04, 0.06, 0.08, and 0.10 are prepared by spark plasma sintering (SPS) using fine powders of crushed arc-melted buttons. The sintered samples are of a nearly single phase. All the samples exhibit metal-like temperature-dependent electrical resistivity ρ of the order of 10-6–10-5 Ω·m in the measured temperature range. For both NbCoSn1-x
Sb
x
and Nb0.99Ti0.01CoSn1-x
Sb
x
, the ρ values at 320 K rapidly decrease by partial substitution in the range between x=0 and 0.02, and finally reach 5 µΩ·m at x=0.10. The Seebeck coefficient S is appreciably enhanced by partly substituting Nb sites with 1 at. % Ti. The highest power factor is 22×10-4 W·m-1·K-2 for Nb0.99Ti0.01CoSn0.9Sb0.1 at 700 K. The thermal conductivity κ weakly depends on temperature and does not show any peculiar trend upon Sb partial substitution. The dimensionless figure of merit Z
T=S
2
T/ρκ for Nb0.99Ti0.01CoSn0.9Sb0.1 reaches 0.3 at 850 K, which is fourfold that of pure NbCoSn.
Method for Measuring Twist Angle of Nematic Liquid Crystal Cell
Authors: Kuo Li-Yuan , Lee King-Lien , Wu Jin-Jei
Published: November 2006

We propose a simple method for measuring the twist angle of a nematic liquid crystal cell, which is the combination of a transmission method and a reflection method. Our method is an improved “rotation polarizer method” that is not confined by the condition of the liquid crystal phase retardation of Δn
d/λ, where Δn is the refraction index anisotropy, d is the cell thickness and λ is the wavelength of light. The experiment is simulated by DIMOS software, which shows the high accuracy of the measurement method.
Local Crystal Structures of Ge2Sb2Te5 Revealed by the Atomic Pair Distribution Function Analysis
Authors: Shamoto Shin-ichi , Kodama Katsuaki , Iikubo Satoshi , Taguchi Tomitsugu , Yamada Noboru , Proffen Thomas
Published: November 2006

Two types of optical recording crystalline material Ge2Sb2Te5 have been studied by neutron and X-ray powder diffraction measurements. One is the crystalline cubic-phase Ge2Sb2Te5. The other is nanocrystalline-phase Ge2Sb2Te5. In the former, a large atomic displacement of germanium atoms was found by the atomic pair distribution function (PDF) analysis of neutron powder diffraction data. According to the electronic band structure calculation of isoelectronic GeTe, the electrical conductivity at the valence band with holes is not severely affected by the randomness at the cation site, whereas the thermal conductivity is significantly reduced by the randomness. For the nanocrystalline phase, the local crystal structure and the particle size distribution were obtained simultaneously by PDF analysis using a spherical-particle form factor. The lattice parameter is longer than that of the crystalline phase, suggesting an antimony-richer composition than the matrix. This compositional deviation would form the nanoparticle, resulting in nucleation-dominated crystal growth.
Estimation Thermal Expansion Coefficient from Lattice Energy for Inorganic Crystals
Authors: Zhang Siyuan , Li Huiling , Zhou Shihong , Pan Tianqi
Published: November 2006

By using the study of the lattice energy and the structural parameters of binary inorganic crystals, a new parameter reflecting the thermal expansion property has been found, the relation between the linear expansion coefficient and new parameter has been established. A semiempirical method for evaluation of linear expansion coefficient from the lattice energy is presented, and developed to the complex crystals. The estimated values of the linear expansion coefficients of both simple and complex crystals are in good agreement with the experimental values.
Control of Preferential Orientation of Platinum Films on RuO2/SiO2/Si Substrates by Sputtering
Authors: Trinh Bui Nguyen Quoc , Horita Susumu
Published: November 2006

We investigated the preferential orientation of Pt films deposited on RuO2/SiO2/Si substrates at a substrate temperature of 100 °C by RF magnetron sputtering, using only Ar gas without O2 gas. It was found that, for a sputtering power less than 30 W and a sputtering gas pressure of 10 Pa, the Pt(100)-oriented volume ratio over the whole Pt film rapidly increases with film thickness. However, for a sputtering power more than 50 W and the same pressure, the ratio slightly increases with thickness, and it is suppressed by increasing the power. On the other hand, the Pt(111)-oriented volume ratio is smaller and decreases with thickness irrespective of the power, whereas it is increased by decreasing the pressure to 4 Pa at 20 W. From these results, it can be considered that (111)-oriented crystalline growth is mainly driven by the lowest surface energy and that (100)-oriented growth is mainly driven by the strain energy due to intrinsic tensile stress which is increased with thickness and pressure, and decreased with power.
Surface Modification of Poly(tetrafluoroethylene) by Synchrotron Radiation Exposure under Several Kinds of Gas Atmosphere
Authors: Kato Yuri , Kanda Kazuhiro , Haruyama Yuichi , Matsui Shinji
Published: November 2006

The surface modification of poly(tetrafluoroethylene) (PTFE) sheet was carried out by exposing the sheet to synchrotron radiation (SR) ranging 50–1000 eV under O2, H2O and CH3OH gas atmospheres. The wettability of the PTFE surface was found to increase with SR dose under each gas atmosphere. The rate of increase in the wettability of the PTFE surface exposed to SR under the O2 gas atmosphere was higher than those of the PTFE surfaces exposed to SR under the other gas atmospheres. The decrease in the amount of –CF2 component and the presence of –C=O and –OH components were observed on a hydrophilic PTFE surface.
Velocity Control of Cesium Atomic Beam Using Two Frequency-Modulated External-Cavity Diode Lasers
Authors: Hirayama Toru , Sato Shunichi
Published: November 2006

The velocity of a cesium atomic beam was controlled using two broadband frequency-modulated, external-cavity diode lasers. One laser beam was used to decelerate faster atoms and the other was used to accelerate slower atoms. The central velocity of the atoms was readily tuned in a wide range while maintaining the width and peak height of a velocity distribution. In addition, the velocity distribution of cesium atoms was calculated on the basis of the scattering force caused by two frequency-modulated laser beams. The calculated peak ratio was in good agreement with the experimental result.
Floating Gate Metal–Oxide–Semiconductor Capacitor Employing Array of High-Density Nanodots Produced by Protein Supramolecule
Authors: Yamada Kiyohito , Yoshii Shigeo , Kumagai Shinya , Miura Atsushi , Uraoka Yukiharu , Fuyuki Takashi , Yamashita Ichiro
Published: November 2006

An array of high-density 1.8×1012 cm-2 floating nanodots was embedded within a metal–oxide–semiconductor (MOS) capacitor using a cage-shaped protein supramolecule, Listeria ferritin (Lis-fer). A monolayer of Lis-fer with a 4.5 nm ferrihydrite core was adsorbed on a 3 nm tunneling SiO2 layer on a p-Si substrate by 3-aminopropyl-triethoxysilane (APTES) surface modification. The outer protein was selectively removed and the obtained cores were covered with a 20-nm-thick control SiO2 layer and an aluminum electrode. The MOS capacitor was annealed in reducing gas (H2:N2=10:90%), and the embedded cores were reduced to conductive nanodots. The capacitance–voltage characteristics of the MOS capacitor measured at 1 MHz by applying a DC bias voltage from -5 to +5 V showed a clear hysteresis. This result indicates that the array of nanodots produced and positioned by Lis-fer has the ability for electron confinement.
Noble Metal/W(111) Single-Atom Tips and Their Field Electron and Ion Emission Characteristics
Authors: Kuo Hong-Shi , Hwang Ing-Shouh , Fu Tsu-Yi , Lin Yu-Chun , Chang Che-Cheng , Tsong Tien T.
Published: November 2006

We have developed a simple, reliable and reproducible method for preparing single-atom tips. With electrochemical techniques, a very small amount of a noble metal is plated on the surface of a clean W<111> tip. Upon annealing the tip at an appropriate temperature in vacuum, a three-sided {211} pyramid with a single-atom sharpness is formed spontaneously at the tip apex by adsorbate-induced faceting. This tip is both thermally and chemically stable, and can be regenerated several ten times when accidentally damaged. We use a field ion microscope to examine the atomic structure of the tip apex layer by layer and characterize the corresponding electron emission in the field emission mode. Some properties of Ne+ ions emitted from a single-atom tip are also measured, indicating a high brightness and a small extension angle. Many desirable features make the single-atom tips very promising for future particle beam applications in nanoscience and nanotechnology.
Structural Analysis of High-Density Vertically Aligned Carbon Nanotubes Grown by Thermal Chemical Vapor Deposition with Fe/Al Multilayer Catalyst
Authors: Komukai Takuji , Aoki Katsunori , Furuta Hiroshi , Furuta Mamoru , Oura Kenjiro , Hirao Takashi
Published: November 2006

A detailed structural analysis has been carried out on vertically aligned carbon nanotubes (CNTs) formed by thermal chemical vapor deposition (CVD) with an Fe/Al multilayer catalyst on a Si substrate. From the results, it was confirmed that the CNTs are composed of two configurations, namely high-density vertically aligned CNTs formed on the catalyst, followed by randomly oriented thin CNTs with low crystallinity formed on the high-density CNTs. Growth kinetics was proposed by considering the dependence of the CNT growth rate on the size of catalyst grains.
Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes
Authors: Juurinen Leena , Tiikkainen Mirja , Häkkinen Anna-Maija , Hakkarainen Antti , Yki-Järvinen Hannele
Published: November 2006

We determined whether insulin therapy changes liver fat content (LFAT) or hepatic insulin sensitivity in type 2 diabetes. Fourteen patients with type 2 diabetes (age 51 ± 2 yr, body mass index 33.1 ± 1.4 kg/m2) treated with metformin alone received additional basal insulin for 7 mo. Liver fat (proton magnetic resonance spectroscopy), fat distribution (MRI), fat-free and fat mass, and whole body and hepatic insulin sensitivity (6-h euglycemic hyperinsulinemic clamp combined with infusion of [3-3H]glucose) were measured. The insulin dose averaged 75 ± 10 IU/day (0.69 ± 0.08 IU/kg, range 24–132 IU/day). Glycosylated hemoglobin A1c(Hb A1c) decreased from 8.9 ± 0.3 to 7.4 ± 0.2% ( P < 0.001). Whole body insulin sensitivity increased from 2.21 ± 0.38 to 3.08 ± 0.40 mg/kg fat-free mass (FFM)·min ( P < 0.05). This improvement could be attributed to enhanced suppression of hepatic glucose production (HGP) by insulin (HGP 1.04 ± 0.28 vs. 0.21 ± 0.19 mg/kg FFM·min, P < 0.01). The percent suppression of HGP by insulin increased from 72 ± 8 to 105 ± 11% ( P < 0.01). LFAT decreased from 17 ± 3 to 14 ± 3% ( P < 0.05). The change in LFAT was significantly correlated with that in hepatic insulin sensitivity ( r = 0.56, P < 0.05). Body weight increased by 3.0 ± 1.1 kg ( P < 0.05). Of this, 83% was due to an increase in fat-free mass ( P < 0.01). Fat distribution and serum adiponectin concentrations remained unchanged while serum free fatty acids decreased significantly. Conclusions: insulin therapy improves hepatic insulin sensitivity and slightly but significantly reduces liver fat content, independent of serum adiponectin.
Energy conservation attenuates the loss of skeletal muscle excitability during intense contractions
Authors: Macdonald W. A. , Ørtenblad N. , Nielsen O. B.
Published: November 2006

High-frequency stimulation of skeletal muscle has long been associated with ionic perturbations, resulting in the loss of membrane excitability, which may prevent action potential propagation and result in skeletal muscle fatigue. Associated with intense skeletal muscle contractions are large changes in muscle metabolites. However, the role of metabolites in the loss of muscle excitability is not clear. The metabolic state of isolated rat extensor digitorum longus muscles at 30°C was manipulated by decreasing energy expenditure and thereby allowed investigation of the effects of energy conservation on skeletal muscle excitability. Muscle ATP utilization was reduced using a combination of the cross-bridge cycling blocker N-benzyl- p-toluene sulfonamide (BTS) and the SR Ca2+ release channel blocker Na-dantrolene, which reduce activity of the myosin ATPase and SR Ca2+-ATPase. Compared with control muscles, the resting metabolites ATP, phosphocreatine, creatine, and lactate, as well as the resting muscle excitability as measured by M-waves, were unaffected by treatment with BTS plus dantrolene. Following 20 or 30 s of continuous 60-Hz stimulation, BTS-plus-dantrolene-treated muscles showed a 25% lower ATP utilization compared with control muscles. Furthermore, the ability of muscles to maintain excitability during high-frequency stimulation was significantly improved in BTS-plus-dantrolene-treated muscles, indicating a strong link between metabolites, energetic state, and the excitability of the muscle.
Network Mechanisms of Spindle-Burst Oscillations in the Neonatal Rat Barrel Cortex In Vivo
Authors: Minlebaev Marat , Ben-Ari Yehezkel , Khazipov Rustem
Published: November 2006

Early in development, cortical networks generate particular patterns of activity that participate in cortical development. The dominant pattern of electrical activity in the neonatal rat neocortex in vivo is a spatially confined spindle-burst. Here, we studied network mechanisms of generation of spindle-bursts in the barrel cortex of neonatal rats using a superfused cortex preparation in vivo. Both spontaneous and sensory-evoked spindle-bursts were present in the superfused barrel cortex. Pharmacological analysis revealed that spindle-bursts are driven by glutamatergic synapses with a major contribution of AMPA/kainate receptors, but slight participation of NMDA receptors and gap junctions. Although GABAergic synapses contributed minimally to the pacing the rhythm of spindle-burst oscillations, surround GABAergic inhibition appeared to be crucial for their compartmentalization. We propose that local spindle-burst oscillations, driven by glutamatergic synapses and spatially confined by GABAergic synapses, contribute to the development of barrel cortex during the critical period of developmental plasticity.
Neuronal Substrates of Motor Learning in the Velocity Storage Generated During Optokinetic Stimulation in the Squirrel Monkey
Authors: Blazquez Pablo M. , de Carrizosa Maria A. Davis-Lopez , Heiney Shane A. , Highstein Stephen M.
Published: November 2006

Chronic motor learning in the vestibuloocular reflex (VOR) results in changes in the gain of this reflex and in other eye movements intimately associated with VOR behavior, e.g., the velocity storage generated by optokinetic stimulation (OKN velocity storage). The aim of the present study was to identify the plastic sites responsible for the change in OKN velocity storage after chronic VOR motor learning. We studied the neuronal responses of vertical eye movement flocculus target neurons (FTNs) during the optokinetic afternystagmus (OKAN) phase of the optokinetic response (OKR) before and after VOR motor learning. Our findings can be summarized as follows. 1) Chronic VOR motor learning changes the horizontal OKN velocity storage in parallel with changes in VOR gain, whereas the vertical OKN velocity storage is more complex, increasing with VOR gain increases, but not changing following VOR gain decreases. 2) FTNs contain an OKAN signal having opposite directional preferences after chronic high versus low gain learning, suggesting a change in the OKN velocity storage representation of FTNs. 3) Changes in the eye-velocity sensitivity of FTNs during OKAN are correlated with changes in the brain stem head-velocity sensitivity of the same neurons. And 4) these changes in eye-velocity sensitivity of FTNs during OKAN support the new behavior after high gain but not low gain learning. Thus we hypothesize that the changes observed in the OKN velocity storage behavior after chronic learning result from changes in brain stem pathways carrying head velocity and OKN velocity storage information, and that a parallel pathway to vertical FTNs changes its OKN velocity storage representation following low, but not high, gain VOR motor learning.
Neurophysiology of Prehension. II. Response Diversity in Primary Somatosensory (S-I) and Motor (M-I) Cortices
Authors: Gardner Esther P. , Ro Jin Y. , Babu K. Srinivasa , Ghosh Soumya
Published: November 2006

Prehension responses of 76 neurons in primary somatosensory (S-I) and motor (M-I) cortices were analyzed in three macaques during performance of a grasp and lift task. Digital video recordings of hand kinematics synchronized to neuronal spike trains were compared with responses in posterior parietal areas 5 and AIP/7b (PPC) of the same monkeys during seven task stages: 1) approach, 2) contact, 3) grasp, 4) lift, 5) hold, 6) lower, and 7) relax. S-I and M-I firing patterns signaled particular hand actions, rather than overall task goals. S-I responses were more diverse than those in PPC, occurred later in time, and focused primarily on grasping. Sixty-three percent of S-I neurons fired at peak rates during contact and/or grasping. Lift, hold, and lowering excited fewer S-I cells. Only 8% of S-I cells fired at peak rates before contact, compared with 27% in PPC. M-I responses were also diverse, forming functional groups for hand preshaping, object acquisition, and grip force application. M-I activity began ≤500 ms before contact, coinciding with the earliest activity in PPC. Activation of specific muscle groups in the hand was paralleled by matching patterns of somatosensory feedback from S-I needed for efficient performance. These findings support hypotheses that predictive and planning components of prehension are represented in PPC and premotor cortex, whereas performance and feedback circuits dominate activity in M-I and S-I. Somatosensory feedback from the hand to S-I enables real-time adjustments of grasping by connections to M-I and updates future prehension plans through projections to PPC.
New Potential Ligand-Receptor Signaling Loops in Ovarian Cancer Identified in Multiple Gene Expression Studies
Authors: Castellano Giancarlo , Reid James F. , Alberti Paola , Carcangiu Maria Luisa , Tomassetti Antonella , Canevari Silvana
Published: November 2006

Based on the hypothesis that gene products involved in the same biological process would be coupled at transcriptional level, a previous study analyzed the correlation of the gene expression patterns of ligand-receptor (L-R) pairs to discover potential autocrine/paracrine signaling loops in different cancers (Graeber and Eisenberg. Nat Genet 2001; 29:295). By refining the starting database, a list of 511 L-R pairs was compiled, combined to eight data sets from a single pathology, epithelial ovarian cancer, and examined as a proof-of-principle of the statistical and biological validity of the correlation of the L-R gene expression patterns in cancer. Analysis revealed a Bonferroni-corrected significant correlation of 105 L-R pairs in at least one data set and, by systematic analysis, identified 39 more frequently correlated L-R pairs, 7 of which were already biologically confirmed. In four data sets examined for an L-R correlation associated with patient survival time, 15 L-R pairs were significantly correlated in short surviving patients in two of the data sets. Immunohistochemical analysis of one of the newly identified correlated L-R pairs (i.e., EFNB3-EPHB4) revealed the correlated expression of ephrin-B3 and EphB4 proteins in 45 of 55 epithelial ovarian tumor samples (P < 0.0001). Together, these data not only support the validity of cross-comparison analysis of gene expression data because known and expected correlations were confirmed but also point to the promise of such analysis in identifying new L-R signaling loops in cancer. (Cancer Res 2006; 66(22): 10709-19)
Ethnic Norms and Interethnic Violence: Accounting for Mass Participation in the Rwandan Genocide
Authors: Bhavnani Ravi
Published: November 2006

This article specifies a simple mechanism - a behavioral norm defined in ethnic terms - to understand the dynamics of mass participation by reluctant Hutu in the 1994 Rwandan genocide. The mechanism, which has not been analyzed systematically in the scholarly literature, is specified using an agent-based model of within-group interaction that captures the role of intra-Hutu coercion in precipitating genocidal violence, yet is general enough to be applied to other group conflicts and contexts. The model highlights the role of individual heterogeneity, within-group punishment, behavioral adaptation, group networks, and ethnic entrepreneurs, and generates a set of results on norm formation and change, a number of which are not intuitive. These findings suggest that (1) norms are not equally likely to form in groups with similar aggregate preference; (2) a violence-promoting norm can emerge in a group dominated by moderates, and violence is not the inevitable outcome in a group dominated by extremists; (3) strong punishments are a prerequisite for the emergence of norms that promote interethnic violence or cooperation; (4) interaction patterns matter - for example, the segregation of an ethnic group clearly inhibits norm formation; and (5) an ethnic entrepreneur can effectively amplify norm formation within a group in the absence of strong punishment.
Morphological abilities in Hebrew-speaking gradeschoolers from two socioeconomic backgrounds: An analogy task
Authors: Ravid Dorit , Schiff Rachel
Published: November 2006

Morphology, one of the organizing principles of the mental lexicon, is especially important in Hebrew, where word structure expresses a rich array of semantic notions. The current study focuses on morphological skills in Hebrew-speaking gradeschoolers from high-and low-SES backgrounds: 152 high-SES children and 167 low-SES children (2nd, 3rd, 4th, 5th and 6th graders) were administered an analogy task, which required reading complex words and eliciting morphological components from them. Results indicate an early and robust ability of Hebrew-speaking children to perform morphological analogies using both root and pattern morphemes. Most of the erroneous responses in both populations involved morphological strategies rather than the associative semantic strategy. However, low-SES children did less well than high-SES children, and the discrepancy between the two populations was consistent throughout gradeschool. This indicates that low-SES gradeschoolers are at a disadvantage in performing morphological analysis, a critical skill in Hebrew literacy.
An Objective Rating Form to Evaluate Grant Proposals to the Hogg Foundation for Mental Health
Authors: Whaley Arthur L.
Published: November 2006

The lack of support for mental health–related projects by private philanthropy, even among those that express an interest in mental health, is due in large part to the subjectivity of the grant review process. To address this problem, Whaley, Rodriguez, and Alexander developed the Grant Proposal Rating Form (GPRF) to make the grant review process more objective at the Hogg Foundation for Mental Health. The purpose of the current study is to establish the ecological validity of the GPRF by a pilot study of its implementation in the actual grant review process of the foundation. The overall results of this pilot study did not yield consistently favorable psychometric outcomes as the original study by Whaley et al. The implications of these results are discussed.
The Windsor Report: A Theological Commentary
Authors: Marks Darren C.
Published: November 2006

It is argued that the Windsor Report is a new Anglican ecclesiology that attempts to answer problems within more classical and historically induced and offered Anglican ecclesiologies. In order to reflect this new direction, the authors borrowed ideas from several offsetting loci—including Roman Catholic receptio theology of communion and a more classic magisterial Protestant theology of Scripture—and as such has morphed the understanding of how Anglican authority, in all its forms, might look without opting for a Roman or the, as perceived by many as problematic, Protestant Liberal model. It is asked whether there is a polarity in the above theologies and which theme, if any, must assume the central role in articulating Anglican ecclesiology. I offer that it is the tacit theology of Scripture that is the true strength of the Windsor Report and which needs to be clarified in future discussions on Anglican ecclesiology.
Impaired Toll-like receptor 8–mediated IL-6 and TNF-α production in antigen-presenting cells from patients with X-linked agammaglobulinemia
Authors: Sochorová Klára , Horváth Rudolf , Rožková Daniela , Litzman Jiří , Bartůňková Jiřina , Šedivá Anna , Špíšek Radek
Published: November 2006

The critical role of Bruton tyrosine kinase (Btk) in B cells has been documented by the block of B-cell development in X-linked agammaglobulinemia (XLA). Less is known about Btk function in myeloid cells. Several pieces of evidence indicate that Btk is a component of Toll-like receptor (TLR) signaling. We analyzed whether Btk deficiency in XLA is associated with an impaired dendritic cell (DC) compartment or defective TLR signaling. We analyzed the expression of TLRs 1 to 9 on myeloid DCs generated from XLA patients and evaluated their response to activation by specific TLR agonists. We show that XLA patients have normal numbers of circulating DCs. Btk-deficient DCs have no defect in response to stimulation of TLRs 1/2, 2/6, 3, 4, and 5 but display a profound impairment of IL-6 and TNF-α production in response to stimulation by TLR-8 cognate agonist, ssRNA. These findings may provide an explanation for the susceptibility to enteroviral infections in XLA patients.
Automated recognition of malignancy mentions in biomedical literature
Authors: Jin Yang , McDonald Ryan T , Lerman Kevin , Mandel Mark A , Carroll Steven , Liberman Mark Y , Pereira Fernando C , Winters Raymond S , White Peter S
Published: November 2006

Background

The rapid proliferation of biomedical text makes it increasingly difficult for researchers to identify, synthesize, and utilize developed knowledge in their fields of interest. Automated information extraction procedures can assist in the acquisition and management of this knowledge. Previous efforts in biomedical text mining have focused primarily upon named entity recognition of well-defined molecular objects such as genes, but less work has been performed to identify disease-related objects and concepts. Furthermore, promise has been tempered by an inability to efficiently scale approaches in ways that minimize manual efforts and still perform with high accuracy. Here, we have applied a machine-learning approach previously successful for identifying molecular entities to a disease concept to determine if the underlying probabilistic model effectively generalizes to unrelated concepts with minimal manual intervention for model retraining.

Results

We developed a named entity recognizer (MTag), an entity tagger for recognizing clinical descriptions of malignancy presented in text. The application uses the machine-learning technique Conditional Random Fields with additional domain-specific features. MTag was tested with 1,010 training and 432 evaluation documents pertaining to cancer genomics. Overall, our experiments resulted in 0.85 precision, 0.83 recall, and 0.84 F-measure on the evaluation set. Compared with a baseline system using string matching of text with a neoplasm term list, MTag performed with a much higher recall rate (92.1% vs. 42.1% recall) and demonstrated the ability to learn new patterns. Application of MTag to all MEDLINE abstracts yielded the identification of 580,002 unique and 9,153,340 overall mentions of malignancy. Significantly, addition of an extensive lexicon of malignancy mentions as a feature set for extraction had minimal impact in performance.

Conclusion

Together, these results suggest that the identification of disparate biomedical entity classes in free text may be achievable with high accuracy and only moderate additional effort for each new application domain.
Mitochondrial oxidative stress and nitrate tolerance – comparison of nitroglycerin and pentaerithrityl tetranitrate in Mn-SOD+/-mice
Authors: Mollnau Hanke , Wenzel Philip , Oelze Matthias , Treiber Nicolai , Pautz Andrea , Schulz Eberhard , Schuhmacher Swenja , Reifenberg Kurt , Stalleicken Dirk , Scharffetter-Kochanek Karin , Kleinert Hartmut , Münzel Thomas , Daiber Andreas
Published: November 2006

Background

Chronic therapy with nitroglycerin (GTN) results in a rapid development of nitrate tolerance which is associated with an increased production of reactive oxygen species (ROS). According to recent studies, mitochondrial ROS formation and oxidative inactivation of the organic nitrate bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) play an important role for the development of nitrate and cross-tolerance.

Methods

Tolerance was induced by infusion of wild type (WT) and heterozygous manganese superoxide dismutase mice (Mn-SOD+/-) with ethanolic solution of GTN (12.5 μg/min/kg for 4 d). For comparison, the tolerance-free pentaerithrityl tetranitrate (PETN, 17.5 μg/min/kg for 4 d) was infused in DMSO. Vascular reactivity was measured by isometric tension studies of isolated aortic rings. ROS formation and aldehyde dehydrogenase (ALDH-2) activity was measured in isolated heart mitochondria.

Results

Chronic GTN infusion lead to impaired vascular responses to GTN and acetylcholine (ACh), increased the ROS formation in mitochondria and decreased ALDH-2 activity in Mn-SOD+/- mice. In contrast, PETN infusion did not increase mitochondrial ROS formation, did not decrease ALDH-2 activity and accordingly did not lead to tolerance and cross-tolerance in Mn-SOD+/- mice. PETN but not GTN increased heme oxygenase-1 mRNA in EA.hy 926 cells and bilirubin efficiently scavenged GTN-derived ROS.

Conclusion

Chronic GTN infusion stimulates mitochondrial ROS production which is an important mechanism leading to tolerance and cross-tolerance. The tetranitrate PETN is devoid of mitochondrial oxidative stress induction and according to the present animal study as well as numerous previous clinical studies can be used without limitations due to tolerance and cross-tolerance.
Barriers in phase I cancer clinical trials referrals and enrollment: five-year experience at the Princess Margaret Hospital
Authors: Ho Jeremy , Pond Gregory R , Newman Colin , Maclean Martha , Chen Eric X , Oza Amit M , Siu Lillian L
Published: November 2006

Background

There is a paucity of literature on the referral outcome of patients seen in phase I trial clinics in academic oncology centres. This study aims to provide information on the accrual rate and to identify obstacles in the recruitment process.

Methods

A retrospective chart review was performed for all new patients referred and seen in the phase I clinic at the Princess Margaret Hospital between January 2000 and June 2005. Data on their demographics, medical history, and details of trial participation or non-entry were recorded.

Results

A total of 667 new phase I referrals were seen during the stated period. Of these patients, 197 (29.5%) patients were enrolled into a phase I trial, and 64.5% of them started trial within 1 month of the initial visit. About a quarter (165 of 667) of the patients referred were deemed ineligible at their first visit, with the most frequent reasons for ineligibility being poor performance status, unacceptable bloodwork, too many prior treatments and rapid disease progression. The remaining 305 patients (45.7%) were potentially eligible at their initial visit, but never entered a phase I trial. The main reasons for their non-entry were patient refusal, other treatment recommended first, and lack of available trials or trial spots.

Conclusion

This study provides information on the clinical realities underlying a referral to a phase I clinic and eventual trial enrollment. Better selection of patients, appropriate education of referring physicians, and opening phase I trials with fewer restrictions on some criteria such as prior therapy may enhance their recruitment rates.
Validity of the Walter Reed Visual Assessment Scale to measure subjective perception of spine deformity in patients with idiopathic scoliosis
Authors: Pineda Sonia , Bago Juan , Gilperez Carmen , Climent Jose M
Published: November 2006

Background

The Walter Reed Visual Assessment Scale (WRVAS) was designed to allow idiopathic scoliosis patients to describe their perception of their deformity. In a previous stduy, the scale has shown good correlation with magnitude of the curve

Methods

The study included 70 patients (60 women and 10 men), mean age 19.4 years (range 12–40), with idiopathic scoliosis. Each patient filled out the WRVAS and the SRS-22 questionnaire. Thoracic and lumbar curve angles were determined in standing X-rays and the largest was named Cobbmax. WRVAS internal consistency was assessed with Cronbach's alpha. Correlation coefficients were calculated between Cobbmax and the various WRVAS questions, and Cobbmax and the SRS-22 scales. The correlation between the WRVAS and SRS-22 was also determined

Results

Mean magnitudes were thoracic curve, 36.6° and lumbar curve, 33.2°; average Cobbmax was 37.9°. The mean total WRVAS score was 15.6. Mean scores for the various SRS-22 scales were function 4.6, pain 4.3, self-image 3.7, mental health 4.2, and total score 84.1. Internal consistency for the WRVAS was excellent (Cronbach's alpha, 0.9), and there were no signs of collinearity among the seven questions (tolerance range 0.2–0.5). All the items on the WRVAS correlated significantly with Cobbmax (correlation coefficients, 0.4 to 0.7). The correlation between the total WRVAS and total SRS-22 score was -0.54 (P = .0001) and between WRVAS total score and SRS-22 image domain score was -0.57 (p = 0.0001)

Conclusion

The WRVAS showed excellent internal consistency and absence of collinearity. There was a highly significant correlation between the results of the test and the magnitude of the deformity. The WRVAS correlated significantly with the SRS-22 image scale. The WRVAS is a valid instrument to assess scoliosis patients perception of their deformity
Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder
Authors: Müller Daniel J. , De Luca Vincenzo , Sicard Tricia , King Nicole , Strauss John , Kennedy James L.
Published: November 2006

Background

We have previously reported the Val66Met and GT(n) repeat polymorphisms of the brain-derived neurotrophic factor (BDNF) gene to be associated with bipolar disorder. However, these findings have not been replicated consistently.

Aims

To dissect the association of the BDNF gene with bipolar disorder by examining additional markers at the DNA level and by testing the illness categories of bipolar disorder I and II and rapid cycling.

Method

We performed a family-based association study and haplotype analyses with 312 nuclear families using four single nucleotide polymorphisms (SNPs) and the Val66Met and GT(n) repeat polymorphisms.

Results

The SNPs hCVI1592756 and rs2049045, the Val66Met and GT(n) were significantly associated with bipolar disorder using transmission disequilibrium analyses (P=0.02, 0.009, 0.001 and 0.008 respectively). The effect at these markers was mainly driven by the rapid-cycling patients.

Conclusions

Within bipolar disorder, variation in the BDNF gene appears to predict risk for developing rapid cycling according to DSM–IV. Incorporating this clinical sub-phenotyping into other studies of the BDNF gene may help to resolve some of the inconsistencies reported thus far concerning BDNF and bipolar disorder.
Promoting Health and Physical Function Among Cancer Survivors: Potential for Prevention and Questions That Remain
Authors: Demark-Wahnefried Wendy , Pinto Bernardine M. , Gritz Ellen R.
Published: November 2006

Cancer survivors are at increased risk, not only for progressive and recurrent disease, but also other cancers, cardiovascular disease, diabetes, osteoporosis, and functional decline. Lifestyle interventions to improve dietary and physical activity behaviors, and smoking cessation, have the potential to improve the overall health and quality of life of this vulnerable population. Studies on overall health and physical function from 1966 and beyond regarding the impact of behavioral interventions that used randomized and controlled designs were identified through MEDLINE and PubMed searches. Published reports currently exist for 22 exercise interventions, 11 diet-related interventions (excluding those limited to dietary supplements or single nutrients), two diet and exercise interventions, and 10 behavioral-based smoking cessation interventions. Although many interventions have been successful in promoting behavioral change and have resulted in improvements in various health-related outcomes, more research is needed to determine the key components of interventions that are able to produce the greatest behavioral change and the most favorable health-related benefits. The oncology care provider can play a pivotal role in improving the long-term health of cancer survivors by (1) being aware of opportunities to encourage healthful behaviors (ie, smoking cessation, weight control, and increased physical activity); (2) vigilantly tracking long-term effects among cancer survivors and exploring whether they are amenable to intervention; (3) staying abreast of current health behavior guidelines for cancer survivors and existing resources for professional and patient education; and (4) supporting and contributing to efforts aimed at primary and tertiary prevention research.
Insights into cytoskeletal behavior from computational modeling of dynamic microtubules in a cell-like environment
Authors: Gregoretti Ivan V. , Margolin Gennady , Alber Mark S. , Goodson Holly V.
Published: November 2006

Microtubule dynamic instability plays a fundamental role in cell biology, enabling microtubules to find and interact with randomly distributed cargo and spatially localized signals. In vitro, microtubules transition between growth and shrinkage symmetrically, consistent with the theoretical understanding of the mechanism of dynamic instability. In vivo, however, microtubules commonly exhibit asymmetric dynamic instability, growing persistently in the cell interior and experiencing catastrophe near the cell edge. What is the origin of this behavior difference? One answer is that the cell edge causes the asymmetry by inducing catastrophe in persistently growing microtubules. However, the origin of the persistent growth itself is unclear. Using a simplified coarse-grained stochastic simulation of a system of dynamic microtubules, we provide evidence that persistent growth is a predictable property of a system of nucleated, dynamic, microtubules containing sufficient tubulin in a confined space – MAP activity is not required. Persistent growth occurs because cell-edge-induced catastrophe increases the concentration of free tubulin at steady-state. Our simulations indicate that other aspects of MT dynamics thought to require temporal or spatial changes in MAP activity are also predictable, perhaps unavoidable, outcomes of the `systems nature' of the cellular microtubule cytoskeleton. These include the mitotic increase in microtubule dynamics and the observation that defects in nucleation cause changes in the behavior of microtubule plus ends. These predictions are directly relevant to understanding of the microtubule cytoskeleton, but they are also attractive from an evolutionary standpoint because they provide evidence that apparently complex cellular behaviors can originate from simple interactions without a requirement for intricate regulatory machinery.
Actin regulation in endocytosis
Authors: Smythe Elizabeth , Ayscough Kathryn R.
Published: November 2006

Increasing evidence from a variety of cell types has highlighted the importance of the actin cytoskeleton during endocytosis. No longer is actin viewed as a passive barrier that must be removed to allow endocytosis to proceed. Rather, actin structures are dynamically organised to assist the remodelling of the cell surface to allow inward movement of vesicles. The majority of our mechanistic insight into the role of actin in endocytosis has come from studies in budding yeast. Although endocytosis in mammalian cells is clearly more complex and subject to a greater array of regulatory signals, recent advances have revealed actin, and actin-regulatory proteins, to be present at endocytic sites. Furthermore, live cell imaging indicates that spatiotemporal aspects of actin recruitment and vesicle formation are likely to be conserved across eukaryotic evolution.
β-catenin relieves I-mfa-mediated suppression of LEF-1 in mammalian cells
Authors: Pan Weijun , Jia Yingying , Huang Tao , Wang Jiyong , Tao Donglei , Gan Xiaoqing , Li Lin
Published: November 2006

We have previously shown that β-catenin interacts with a transcription suppressor I-mfa and, through this interaction, canonical Wnt signaling could relieve I-mfa-mediated suppression of myogenic regulatory factors (MRFs). In this study, we found that, based on this interaction, I-mfa-mediated suppression of the Wnt transcription factor T-cell factor/lymphoid enhancing factor-1 (TCF/LEF-1) can also be relieved. Our work showed that knocking down endogenous I-mfa expression mimics canonical Wnt treatment by inducing myogenesis and increasing Wnt reporter gene activity, endogenous Wnt target gene expression and expression of MRFs in P19 cells. More importantly, these I-mfa small interfering RNA (siRNA)-induced effects could be blocked by a dominant-negative mutant of LEF-1, confirming the involvement of the TCF/LEF-1 pathway. In addition, we found that β-catenin could compete with I-mfa for binding to LEF-1 and relieve the inhibitory effects of I-mfa in overexpression systems. Furthermore, canonical Wnt was able to reduce the levels of endogenous I-mfa associated with LEF-1, while increasing that of I-mfa associated with β-catenin. All of the evidence supports a conclusion that I-mfa can suppress myogenesis by inhibiting TCF/LEF-1 and that canonical Wnt signaling may relieve the suppression through elevating β-catenin levels, which in turn relieve I-mfa-mediated suppression.
p63 is upstream of IKKα in epidermal development
Authors: Candi Eleonora , Terrinoni Alessandro , Rufini Alessandro , Chikh Anissa , Lena Anna Maria , Suzuki Yasuhiro , Sayan Berna S. , Knight Richard A. , Melino Gerry
Published: November 2006

The epidermis, the outer layer of the skin composed of keratinocytes, develops following the action of the transcription factor p63. The mouse Trp63 gene contains two promoters, driving the production of distinct proteins, one with an N-terminal trans-activation domain (TAp63) and one without (ΔNp63), although their relative contribution to epidermal development is not clearly established. To identify the relative role of p63 isoforms in relation to IKKα, also known to be essential for epithelial development, we performed both molecular and in vivo analyses using genetic complementation in mice. We found that the action of TAp63 is mediated at the molecular level by direct and indirect transactivation of IKKα and Ets-1, respectively. We also found that ΔNp63 upregulates IKKα indirectly, through GATA-3. Our data are consistent with a role for p63 directly upstream of IKKα in epithelial development.
Cinderella no longer: α-catenin steps out of cadherin's shadow
Authors: Scott Jeanie A. , Yap Alpha S.
Published: November 2006

To date, α-catenin has been best understood as an important cytoplasmic component of the classical cadherin complex responsible for cell-cell adhesion. By virtue of its capacity to bind F-actin, α-catenin was commonly envisaged to support cadherin function by coupling the adhesion receptor to the actin cytoskeleton. But is α-catenin solely the cadherin's handmaiden? A range of recent developments suggest, instead, that its biological activity is much more complex than previously appreciated. Evidence from cellular systems and model organisms demonstrates a clear, often dramatic, role for α-catenin in tissue organization and morphogenesis. The morphogenetic impact of α-catenin reflects its capacity to mediate functional cooperation between cadherins and the actin cytoskeleton, but is not confined to this. α-Catenin has a role in regulating cell proliferation and cadherin-independent pools of α-catenin may contribute to its functional impact.
SPECIAL SECTION: Adapting to New Technology in the Operating Room
Authors: Cook Richard I. , Woods David D.
Published: November 2006

The effects of new technology on human performance in domains such as anesthesiology, commercial aviation, and nuclear power operations remain controversial. To study the impact of new technology on skilled practitioner performance, we observed the introduction of a new, highly integrated, microprocessor-based physiological monitoring system for use in cardiac anesthesia. The new computer system differed from its predecessors in method of display, human interface, level of integration, and automation of functions. A process-tracing technique was used to examine physician-computer interaction in the context of 22 anesthesia procedures for cardiothoracic surgery, most of which involved cardiopulmonary bypass. Practitioners experienced a series of problems with the new computer system. Computer system characteristics relative to the specific context of cardiac surgery created new cognitive and physical burdens that tended to congregate at times of high demand, the characteristic feature of clumsy automation. Practitioners as individuals and as a group tried to overcome these problems by adapting the computer system ( system tailoring) and their behavior ( task tailoring) as they learned about the interaction between characteristics of the new system and characteristics of their field of practice.