bluuebunny/crossref_metadata_2025 huggingface dataset:
Doubly Doped Bi2O3 Electrolytes with Higher Conductivity
Authors: Jung Doh Won , Duncan Keith , Wachsman E. D.
Published: November 2006

Bi2O3 electrolytes doubly doped with Dy2O3 and WO3 (DyWSB) were developed to obtain high ionic conductivity. Various compositions having 2:1 mol dopant ratio between Dy and W were tested to obtain a pure single phase, and the trend in conductivity according to total dopant concentration determined. The dopants were selected based on their radii and polarizability. The conductivity of DyWSB electrolytes increases linearly as the total dopant concentration decreases with fixed dopant ratio. The conductivity of 8Dy4WSB is 0.098 S/cm (4 times higher than that of 20ErSB) at 500oC, and the conductivity is 0.569 S/cm at 700oC.
A NOx Sensor Using Solid Electrolyte Impedance Transducer and Perovskite-Type Oxide Receptor
Authors: Shimizu Youichi , Koba Daisuke , Saitoh Hiroaki , Takase Satoko
Published: November 2006

Impedance-type new all-solid-state ceramic NOx sensor has been developed using solid-electrolyte and oxide receptor. The electrochemical device composed of Li1.5Al0.5Ti1.5(PO4)3 (LATP) and perovskite-type oxide LaBO3 (B= Co, Cr, Ni, Mn, Fe) as the transducer and the receptor, respectively, have been systematically investigated for the detection of NOx (NO, NO2 and N2O) in the range 10 - 2000ppm at 400 - 500 {degree sign} C. Among the sensor devices tested, those using LaCoO3-, and LaCrO3 based receptor gave good selectivity to NO. The LaNiO3/LATP based sensor element showed excellent NOx sensing properties.
The Effect of LSM Nanoparticles on SOFC Cathode Performance
Authors: Birss V. I. , Fournier Joseph
Published: November 2006

Nanoparticles of La1-xSrxMnO3{plus minus}¸ (LSM) were developed in the hopes that their high surface area would translate into enhanced oxygen reduction (ORR) kinetics when used as SOFC cathode materials. A novel sol gel derived synthesis was developed to produce both powders and a sol of LSM. Two distinct cathode fabrication approaches were utilized in this work in an effort to test the effects of sintering temperature. The first involved the pre-calcination of LSM nanopowders at 900 åC that were than subjected to the same high temperatures commonly used to sinter micron-sized LSM:YSZ electrodes. The second made use of a two stage sintering process, where the nano LSM component was introduced into a pre-sintered YSZ matrix by a liquid phase impregnation technique, which was followed by low temperature calcination. A comparison of the electrochemical activities between conventional LSM and LSM:YSZ cathodes has shown that higher ORR rates are obtainable by utilization of LSM nanoparticles.
Combustion Synthesis and Characterization of Pr0.8Sr0.2Co1-xFexO3 Nanocrystalline Powders
Authors: Magnone Edoardo , Miyayama Masaru , Traversa E.
Published: November 2006

Different sets of perovskite-type oxides of general formula Pr0.8Sr0.2Co1-xFexO3 (x = 0.0, 0.2, 0.5, 0.8 and 1.0) were successfully prepared by the amorphous citrate method and auto- combustion synthesis at low temperature. Simultaneous thermogravimetric and differential thermal analysis (TG-DTA) was carried out on dried precursor gels to determine the perovskite-phase formation process, and thus discriminate the ignition temperature, actual combustion temperature, and temperature synthesis of the oxide. The calcination behaviour was studied at temperatures up to 1273 K. Single-phase nanocrystalline powders were obtained with controllable grain size from 30 to 100 nm as a function of the heating. Induced couple plasma (ICP) spectroscopy results indicated that for the prepared samples the actual metal contents were nearly equal to the nominal values. X-Ray diffraction (XRD) results showed that Pr0.8Sr0.2Co1-xFexO3 as-combusted compounds possessed a rhombohedral to orthorhombic structure, depending on the iron content. Composition dependence of lattice constants was observed to follow the Vegard's law. Moreover, the perovskite-type nano-powder oxides were characterized as electrodes on Ce0.8Sm0.2O2-x pellets in symmetrical cells, and the electrochemical properties of the electrode/electrolyte interfaces were investigated using electrochemical impedance spectroscopy (EIS).
The Inhibition Activity of Low- and High-Molecular Compounds with Triazole Cycle under Acidic Iron Corrosion
Authors: Kaluzhina Svetlana A. , Neupokoeva Evgenia I.
Published: November 2006

There are literature data about using the benzotriazole (BTA) and triazole (TA) as the inhibitors of acidic iron corrosion. Triazol-dicarbonic acid (TDA), its butyl ether (BEA) and vinyl triazoles with different viscosities (PVT-1, PVT-2, PVT-4) are the substances, the inhibition activity of which has not been considered earlier and it's analysed for the first time in the present work. It has shown, that studied substances inhibit the iron corrosion in 0.05M H2SO4, especially under high temperature. The optimum concentrations of inhibitors, providing the maximum protective effect, have been sorted out. The mechanism of inhibition action of triazole compounds was considered. It was established, that all investigated substances are high-temperature cathodic inhibitors of iron corrosion and their protective properties are connected with adsorption on metal surface
Degradation of Organic Coatings on Steel Investigated by Dynamic Electrochemical Impedance Spectroscopy
Authors: Itagaki Masayuki , Ono Akira , Watanabe Kunihiro , Katayama Hideki , Noda Kazuhiko
Published: November 2006

Degradation of the organic coatings on steel has been investigated by the dynamic impedance measurements. The dynamic impedance was displayed on 3-dimension plots, whose axes were real and imaginary components and time. The time variation of the film resistance related to the permeation of water was monitored to discuss the corrosion mechanisms of coated steel.
Fabrication of the Electroless NiMoB Films as a Diffusion Barrier Layer on the Low-k Substrate
Authors: Yoshino Masahiro , Masuda Toyoto , Wakatsuki Satoshi , Sasano Junji , Matsuda Itsuaki , Shacham-Diamand Yosi , Osaka Tetsuya
Published: November 2006

Fabrication of electroless NiMoB thin films as a diffusion barrier layer and capping layer for Cu interconnects in ULSI with low-k inter level dielectrics were developed. The films containing the Mo were expected to improve the barrier property for Cu diffusion and thermal stability of the films. This study included the novel wet formation process, i.e. we use self-assembled monolayer and catalyzing process to obtain the uniform catalyzed surface to initiate the electroless deposition reaction. The deposition rate was strongly dependent on the MoO3 concentration in the solution. The content of Mo in the deposit increased as the concentration of MoO3 in the solution increased. Thermal stability of the NiMoB film for Cu diffusion was evaluated. The obtained films (Mo concentration = 20 to 25at %) was stable against vacuum annealing under 400{degree sign}C
Electromigration in sub-micron Copper Interconnects in Low-k Dielectrics
Authors: Agarwala Birendra , Chanda Kaushik , Rathore H. S. , Nguyen Du , Hu Chao-Kun , Mclaughlin Paul , Demarest James , Clevenger Lawrence , Yang Chih-Chao
Published: November 2006

In the advanced on-chip interconnect Technology, the interconnect reliability has been a subject of utmost importance. As the line width is reduced to the sub -micron range, the current carrying capability of the Cu interconnect lines becomes an important issue. This paper discusses the electromigration behavior of Cu interconnects passivated with low-k dielectrics. The influences of the cap dielectrics, the liner thickness, via /liner contact and multiple via on the EM lifetime are discussed. The data on the EM kinetics are also presented.
Micro-Thermoelectric Gas Sensor with P-doped SiGe Thin Film Deposited by Helicon Sputtering
Authors: Tajima Kazuki , Shin Woosuck , Nishibori Maiko , Itoh Toshio , Izu Noriya , Matsubara Ichiro
Published: November 2006

Micro-thermoelectric hydrogen sensor working with the combination of the thermoelectric effect of phosphorus-doped SiGe thin film and the Pt-catalyzed exothermic reaction of hydrogen oxidation has been fabricated. Sensitivity of hydrogen gas of the device was improved by doping the SiGe thermoelectric thin film deposited by helicon sputtering.
Cardiovascular Risk Reduction in High-Risk Pediatric Patients
Authors: Kavey Rae-Ellen W. , Allada Vivek , Daniels Stephen R. , Hayman Laura L. , McCrindle Brian W. , Newburger Jane W. , Parekh Rulan S. , Steinberger Julia
Published: November 2006

Although for most children the process of atherosclerosis is subclinical, dramatically accelerated atherosclerosis occurs in some pediatric disease states, with clinical coronary events occurring in childhood and very early adult life. As with most scientific statements about children and the future risk for cardiovascular disease, there are no randomized trials documenting the effects of risk reduction on hard clinical outcomes. A growing body of literature, however, identifies the importance of premature cardiovascular disease in the course of certain pediatric diagnoses and addresses the response to risk factor reduction. For this scientific statement, a panel of experts reviewed what is known about very premature cardiovascular disease in 8 high-risk pediatric diagnoses and, from the science base, developed practical recommendations for management of cardiovascular risk.
The Human Striatum is Necessary for Responding to Changes in Stimulus Relevance
Authors: Cools R. , Ivry R. B. , D'Esposito M.
Published: November 2006

Various lines of evidence suggest that the striatum is implicated in cognitive flexibility. The neuropsychological evidence has, for the most part, been based on research with patients with Parkinson's disease, which is accompanied by chemical disruption of both the striatum and the prefrontal cortex. The present study examined this issue by testing patients with focal lesions of the striatum on a task measuring two forms of cognitive switching. Patients with striatal, but not frontal lobe lesions, were impaired in switching between concrete sensory stimuli. By contrast, both patient groups were unimpaired when switching between abstract task rules relative to baseline nonswitch trials. These results reveal a dissociation between two distinct forms of cognitive f lexibility, providing converging evidence for a role of the striatum in f lexible control functions associated with the selection of behaviorally relevant stimuli.
Repetition Suppression for Spoken Sentences and the Effect of Task Demands
Authors: Hasson Uri , Nusbaum Howard C. , Small Steven L.
Published: November 2006

We examined whether the repeated processing of spoken sentences is accompanied by reduced bold oxygenation level-dependent response (repetition suppression) in regions implicated in sentence comprehension and whether the magnitude of such suppression depends on the task under which the sentences are comprehended or on the complexity of the sentences. We found that sentence repetition was associated with repetition suppression in temporal regions, independent of whether participants judged the sensibility of the statements or listened to the statements passively. In contrast, repetition suppression in inferior frontal regions was found only in the context of the task demanding active judgment. These results suggest that repetition suppression in temporal regions reflects facilitation of sentence comprehension processing per se, whereas in frontal regions it reflects, at least in part, easier execution of specific psycholinguistic judgments.
Imaging Informational Conflict: A Functional Magnetic Resonance Imaging Study of Numerical Stroop
Authors: Tang J. , Critchley H. D. , Glaser D. E. , Dolan R. J. , Butterworth B.
Published: November 2006

We employed a parametric version of the comparison Stroop paradigm to investigate the processing of numerical magnitude and physical size under task-relevant and -irrelevant conditions to investigate two theoretical issues: (1) What is the neural fate of task-irrelevant information? (2) What is the neural basis of the resolution of the conflict between task-relevant and -irrelevant information? We show in 18 healthy adults that numerical magnitudes of numbers call for higher processing requirements than physical sizes. The enhanced activation elicited by numerical magnitudes is not modulated by task relevance, indicating autonomous processing. Moreover, the normal behavioral distance effect when the numerical dimension is task relevant and reversed distance effect when it is not show that autonomous processing fully encodes numerical magnitudes. Conflict trials elicited greater activation in bilateral inferior frontal gyri, right middle frontal gyri, and right superior frontal gyri. We postulate two sources to the conflict, namely, at cognitive and response levels.
Notes on A Record of Fear: On the Threshold of the Audible
Authors: Wilson Louise K.
Published: November 2006

The author considers the ideas behind her series of temporary audio (and video) installations collectively entitled A Record of Fear, made for the site of Orford Ness on the Suffolk coast. This remote shingle spit was a covert military testing site for much of the 20th century and is now owned and run by the National Trust. The author worked with three sound recordists to capture ambient and “performed” sounds subsequently used in three separate on-site installations. These pieces were a response to both the site's painful history and its current rich soundscape.
Acoustic, Electric and Virtual Noise: The Cultural Identity of the Guitar
Authors: Carfoot Gavin
Published: November 2006

Guitar technology underwent significant changes in the 20th century in the move from acoustic to electric instruments. In the first part of the 21st century, the guitar continues to develop through its interaction with digital technologies. Such changes in guitar technology are usually grounded in what we might call the “cultural identity” of the instrument: that is, the various ways that the guitar is used to enact, influence and challenge sociocultural and musical discourses. Often, these different uses of the guitar can be seen to reflect a conflict between the changing concepts of “noise” and “musical sound.”
Concert Room
Authors: Kirkegaard Jacob
Published: November 2006

Recording of a concert room inside the abandoned city of Pripyat, in the Chernobyl exclusion zone, October 2005.
Our Streets! Symphonies of Protest
Authors: DeLaurenti Chris
Published: November 2006

Extract from Live in New York at the Republican National Convention Protest September 2–August 28, 2004.
Sound Massages
Authors: Battus Pascal
Published: November 2006

Binaural recording at the Musique et Quotidien Sonore Festival, Albi, France, May 2005.
A Self-Contained Identification Scheme for Eddies in Drifter and Float Trajectories
Authors: Lankhorst Matthias
Published: November 2006

It is becoming increasingly recognized that the eddy field plays an important—possibly dominating—role for oceanic motions in many aspects (e.g., transport of properties and risk assessment in the case of extreme events). This motivates the study of individual eddy events. In the Lagrangian coordinate system, vorticity possibly associated with eddies appears in two forms: as shear vorticity between neighboring particles, and as curvature of the trajectory of a single particle. Typical field experiments in physical oceanography using surface drifters or subsurface floats do not reach data densities high enough to produce enough encounters of drifters to calculate shear vorticity between them. However, curvature in individual tracks is easily observed. This study presents a methodology that extracts segments from within a trajectory that are “looping,” which will be interpreted as a drifter being caught in an eddy. The method makes use of autoregressive processes, a simple type of stochastic processes, which easily enables a fit to the nonperfectly shaped trajectory data usually expected from field experiments. These processes also deliver frequency and persistence of the detected eddies by a very simple calculation, which makes the methodology highly suited for automatized scanning of larger datasets.
The Measurement of the Sea Surface Temperature by Satellites from 1991 to 2005
Authors: O’Carroll Anne G. , Saunders Roger W. , Watts James G.
Published: November 2006

A near-continuous series of global retrievals of sea surface temperature (SST) has been made from the Along-Track Scanning Radiometer (ATSR) series of instruments from 1991 to 2005. To analyze possible long-term trends in the global or regional SST throughout the period daily anomalies are computed using a 1961–90 daily climatology, averaged into global monthly means, and plotted as a global time series. To evaluate any biases in these anomalies they are compared with other satellite SST datasets that have been computed and compared over the same time period. Global infrared satellite SST data have been received from the Advanced Very High Resolution Radiometer (AVHRR) series, microwave SST data from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI), and global microwave SST data from the Advanced Microwave Sounding Radiometer (AMSR)-E on Aqua. Additionally, the anomalies have also been compared with the Hadley Centre Global Sea Ice Coverage and Sea Surface Temperature (HadISST1) anomalies. HadISST1 is a globally complete 1° SST analysis compiled from in situ and bias-corrected AVHRR SSTs at the Met Office (UK).

The results of the study show the high accuracy of the Advanced Along Track Scanning Radiometer (AATSR) SSTs, but there are concerns with the NOAA-14 AVHRR data (1996–2000) being biased cold, especially in the Northern Hemisphere, and the AMSR-E SSTs (version 4), which show unexplained biases. Since 1999 TMI SSTs appear to have a consistently warm (∼0.2 K) bias relative to the infrared sensors and HadISST1.

The time series in (A)ATSR SSTs indicate the possibility of warming trends between 0.1 and 0.2 K decade−1, but the remaining ATSR-1 data are required to confirm this.
Problems with Heavy Snow Data at First-Order Stations in the United States
Authors: Changnon Stanley A.
Published: November 2006

Various interests desire information and data on heavy snowfalls to define their spatial and temporal occurrences. Historical data at the nation’s 208 first-order stations for events with 15.2 cm or more snowfall in 2 days or less was assessed, and revealed various serious data problems at 118 stations with climatological quality data available for 90 stations. The data problems are described as guidelines for those seeking to utilize heavy snowfall data, and stations with quality data are listed.
Infrared Thermal Imagery of Cloud Base in Tornadic Supercells
Authors: Tanamachi Robin L. , Bluestein Howard B. , Moore Stephen S. , Madding Robert P.
Published: November 2006

During the spring seasons of 2003 and 2004, an infrared thermal camera was deployed in and around supercell thunderstorms in an attempt to retrieve the temperature at the cloud base of a mesocyclone prior to tornadogenesis. The motivation for this exercise was to obtain temperature information that might indicate the thermal structure, timing, and extent of the rear-flank downdraft (RFD) and possibly elucidate its relationship to tornadogenesis.

An atmospheric transmissivity study was conducted to account for the effects of atmospheric transmission on the measured temperatures, and to determine an ideal range of distances from which infrared images of a wall cloud or a tornado could be safely captured while still retrieving accurate cloud temperatures. This range was found to be 1.5–3 km.

Two case days are highlighted in which the infrared camera was deployed within 1.5–3 km of a tornado; the visible and infrared images are shown side by side for comparison. On the single occasion on which the tornadogenesis phase was captured, the infrared images show no strong horizontal temperature gradients. From the infrared images taken of tornadoes, it can be inferred that the infrared signal from the tornado consisted primarily of infrared emissions from lofted dust particles or cloud droplets, and that the infrared signal from the tornado condensation funnel was easily obscured by infrared emissions from lofted dust particles or intervening precipitation curtains.

The deployment of the infrared camera near supercell thunderstorms and the analysis of the resulting images proved challenging. It is concluded that the infrared camera is a useful tool for measuring cloud-base temperature gradients provided that distance and viewing angle constraints are met and that the cloud base is unobscured by rain or other intervening infrared emission sources. When these restrictions were met, the infrared camera successfully retrieved horizontal temperature gradients along the cloud base and vertical temperature gradients (close to the moist adiabatic lapse rate) along the tornado funnel.
Influence of Silsesquioxane Coatings on Interfacial and Impact Properties of Carbon Fiber—Polyarylacetylene Composites
Authors: Zhang X.Z. , Huang Y.D. , Wang T.Y. , Liu L.
Published: November 2006

A carbon fiber surface is treated with silsesquioxane (SSO) coatings, including methyl-SSO (MES-SSO), vinyl-SSO (VMS-SSO), and 3-(methacryloxy) propyl-SSO (MPMS-SSO). The mechanical behavior of the carbon fiber—polyarylacetylene (CF—PAA) composites is studied in terms of force modulation mode atomic force microscope (AFM), short-beam bending, microdebonding, and impact tests. A transitional layer appears between the fiber and resin after the carbon fibers are treated with SSO coating. Based on experimental results, The authors conclude that the mechanical interfacial properties of the composites, i.e., interlaminar shear strength (ILSS) and interfacial shear strength (IFSS), are largely increased by the SSO coatings on the fiber surface. Impact properties of the composites are also dominated by SSO coatings. These results could be explained as probably due to the effect of SSO coatings, resulting in improved ductile fracture properties, thereby increasing the resistance to deformation and crack initiation of the polyarylacetylene system.
Establishment of a pipeline to analyse non-synonymous SNPs in Bos taurus
Authors: Lee Michael A , Keane Orla M , Glass Belinda C , Manley Tim R , Cullen Neil G , Dodds Ken G , McCulloch Alan F , Morris Chris A , Schreiber Mark , Warren Jonathan , Zadissa Amonida , Wilson Theresa , McEwan John C
Published: November 2006

Background

Single nucleotide polymorphisms (SNPs) are an abundant form of genetic variation in the genome of every species and are useful for gene mapping and association studies. Of particular interest are non-synonymous SNPs, which may alter protein function and phenotype. We therefore examined bovine expressed sequences for non-synonymous SNPs and validated and tested selected SNPs for their association with measured traits.

Results

Over 500,000 public bovine expressed sequence tagged (EST) sequences were used to search for coding SNPs (cSNPs). A total of 15,353 SNPs were detected in the transcribed sequences studied, of which 6,325 were predicted to be coding SNPs with the remaining 9,028 SNPs presumed to be in untranslated regions. Of the cSNPs detected, 2,868 were predicted to result in a change in the amino acid encoded. In order to determine the actual number of non-synonymous polymorphic SNPs we designed assays for 920 of the putative SNPs. These SNPs were then genotyped through a panel of cattle DNA pools using chip-based MALDI-TOF mass spectrometry. Of the SNPs tested, 29% were found to be polymorphic with a minor allele frequency >10%. A subset of the SNPs was genotyped through animal resources in order to look for association with age of puberty, facial eczema resistance or meat yield. Three SNPs were nominally associated with resistance to the disease facial eczema (P < 0.01).

Conclusion

We have identified 15,353 putative SNPs in or close to bovine genes and 2,868 of these SNPs were predicted to be non-synonymous. Approximately 29% of the non-synonymous SNPs were polymorphic and common with a minor allele frequency >10%. Of the SNPs detected in this study, 99% have not been previously reported. These novel SNPs will be useful for association studies or gene mapping.
Abnormal insulin-like growth factor 1 signaling in human osteoarthritic subchondral bone osteoblasts
Authors: Massicotte Frédéric , Aubry Isabelle , Martel-Pelletier Johanne , Pelletier Jean-Pierre , Fernandes Julio , Lajeunesse Daniel
Published: November 2006

Insulin-like growth factor (IGF)-1 is a key factor in bone homeostasis and could be involved in bone tissue sclerosis as observed in osteoarthritis (OA). Here, we compare the key signaling pathways triggered in response to IGF-1 stimulation between normal and OA osteoblasts (Obs). Primary Obs were prepared from the subchondral bone of tibial plateaus of OA patients undergoing knee replacement or from normal individuals at autopsy. Phenotypic characterization of Obs was evaluated with alkaline phosphatase and osteocalcin release. The effect of IGF-1 on cell proliferation, alkaline phosphatase and collagen synthesis was evaluated in the presence or not of 50 ng/ml IGF-1, whereas signaling was studied with proteins separated by SDS-PAGE before western blot analysis. We also used immunoprecipitation followed by western blot analysis to detect interactions between key IGF-1 signaling elements. IGF-1 receptor (IGF-1R), Shc, Grb2, insulin receptor substrate (IRS)-1, and p42/44 mitogen-activated protein kinase (MAPK) levels were similar in normal and OA Obs in the presence or absence of IGF-1. After IGF-1 stimulation, the phosphorylation of IGF-1R in normal and OA Obs was similar; however, the phosphorylation of IRS-1 was reduced in OA Ob. In addition, the PI3K pathway was activated similarly in normal and OA Obs while that for p42/44 MAPK was higher in OA Obs compared to normal. p42/44 MAPK can be triggered via an IRS-1/Syp or Grb2/Shc interaction. Interestingly, Syp was poorly phosphorylated under basal conditions in normal Obs and was rapidly phosphorylated upon IGF-1 stimulation, yet Syp showed a poor interaction with IRS-1. In contrast, Syp was highly phosphorylated in OA Obs and its interaction with IRS-1 was very strong initially, yet rapidly dropped with IGF-1 treatments. The interaction of Grb2 with IRS-1 progressively increased in response to IGF-1 in OA Obs whereas this was absent in normal Ob. IGF-1 stimulation altered alkaline phosphatase in Ob, an effect reduced in the presence of PD98059, an inhibitor of p42/44 MAPK signaling, whereas neither IGF-1 nor PD98059 had any significant effect on collagen synthesis. In contrast, cell proliferation was higher in OA Obs compared to normal under basal conditions, and IGF-1 stimulated more cell proliferation in OA Obs than in normal Ob, an effect totally dependent on p42/44 MAPK activiy. The altered response of OA Obs to IGF-1 may be due to abnormal IGF-1 signaling in these cells. This is mostly linked with abnormal IRS-1/Syp and IRS-1/Grb2 interaction in these cells.
Association of SUMO4, as a Candidate Gene for IDDM5, with Susceptibility to Type 1 Diabetes in Asian Populations
Authors: NOSO SHINSUKE , IKEGAMI HIROSHI , FUJISAWA TOMOMI , KAWABATA YUMIKO , ASANO KATSUAKI , HIROMINE YOSHIHISA , SUGIHARA SHIGETAKA , LEE INKYU , KAWASAKI EIJI , AWATA TAKUYA , OGIHARA TOSHIO
Published: November 2006

Abstract:  Recent study demonstrated that M55V variant in SUMO4 at IDDM5 was associated with susceptibility to type 1 diabetes. Subsequent studies, however, showed inconsistency in the association. To clarify the population‐wide effect on the association of SUMO4 with type 1 diabetes, we have performed meta‐analysis including our own data in Asian populations, which confirmed a highly significant association in Asian populations (summary odds ratio [OR]: 1.29, P= 7.0 × 10−6), but indicated significant heterogeneity in the genetic effect of the SUMO4 gene on type 1 diabetes among diverse ethnic groups. These observations indicated the association of SUMO4 with type 1 diabetes in Asian populations.
The Gene for Human IL‐21 and Genetic Susceptibility to Type 1 Diabetes in the Japanese
Authors: ASANO KATSUAKI , IKEGAMI HIROSHI , FUJISAWA TOMOMI , KAWABATA YUMIKO , NOSO SHINSUKE , HIROMINE YOSHIHISA , OGIHARA TOSHIO
Published: November 2006

Abstract:  Type 1 diabetes is under polygenic control both in humans and the NOD mouse. Recently a possible role of IL‐21 in the pathogenesis of type 1 diabetes was demonstrated in the NOD mouse. Furthermore, the murine IL‐21 gene is mapped to the Idd3 interval, making the human IL‐21 gene (IL21) a functional as well as positional candidate for susceptibility. We therefore screened sequence variants of IL21 and studied the association with type 1 diabetes. Preliminary data showed no association of IL21 polymorphisms with the disease, suggesting that IL21 plays little role in susceptibility to type 1 diabetes in Japanese.
Genetics of Type 1 Diabetes: Similarities and Differences between Asian and Caucasian Populations
Authors: IKEGAMI HIROSHI , FUJISAWA TOMOMI , KAWABATA YUMIKO , NOSO SHINSUKE , OGIHARA TOSHIO
Published: November 2006

Abstract:  Transracial studies are a powerful tool for genetic association studies of multifactorial diseases, such as type 1 diabetes. We therefore studied the association of candidate genes, HLA, INS, CTLA4, PTPN22, and SUMO4, with type 1 diabetes in Asian populations in comparison with Caucasian populations. Class II HLA was strongly associated with type 1 diabetes in both Asian and Caucasian populations, but alleles associated with type 1 diabetes are different among different ethnic groups due to difference in allele distribution in general populations. INS was associated with type 1 diabetes in both Japanese and Caucasian populations, but frequency of disease‐associated haplotype was markedly higher in Japanese than in Caucasian populations. CTLA4 association was reported for both type 1 diabetes and autoimmune thyroid diseases (AITD) in Caucasian populations, but the association with type 1 diabetes was concentrated in a subset of patients with AITD in Japanese. A variant (R620W) of PTPN22 was consistently associated with type 1 diabetes in Caucasian populations, but the variant was absent in Asian populations including Japanese. M55V variant of SUMO4 was significantly associated with type 1 diabetes in Asians, but genetic heterogeneity between Asian and Caucasian populations was suggested. These data indicate the importance of transracial studies with a large number of samples in each ethnic group in genetic dissection of type 1 diabetes.
Contribution of Class III MHC to Susceptibility to Type 1 Diabetes in the NOD Mouse
Authors: YAMAJI KAORI , IKEGAMI HIROSHI , FUJISAWA TOMOMI , NOSO SHINSUKE , NOJIMA KOJI , BABAYA NARU , ITOI‐BABAYA MICHIKO , KOBAYASHI MISATO , HIROMINE YOSHIHISA , MAKINO SUSUMU , OGIHARA TOSHIO
Published: November 2006

Abstract:  A recombinant major histocompatibility complex (MHC) with the same class III region as the NOD mouse, but different class II region from the NOD mouse was identified in the NON mouse, and NOD mice congenic for this recombinant MHC, NOD.NON‐H2, was established. None of the congenic mice homozygous for the NON MHC developed type 1 diabetes, indicating that the NOD MHC is necessary for the development of type 1 diabetes. A small portion of MHC heterozygotes developed late‐onset type 1 diabetes, suggesting the contribution of class III MHC to type 1 diabetes susceptibility.
MHC‐Linked Susceptibility to Type 1 Diabetes in the NOD Mouse
Authors: FUJISAWA TOMOMI , IKEGAMI HIROSHI , NOSO SHINSUKE , YAMAJI KAORI , NOJIMA KOJI , BABAYA NARU , ITOI‐BABAYA MICHIKO , HIROMINE YOSHIHISA , KOBAYASHI MISATO , MAKINO SUSUMU , OGIHARA TOSHIO
Published: November 2006

Abstract:  Although major histocompatibility complex (MHC)‐linked susceptibility is the strongest component, recent studies demonstrated that MHC‐linked susceptibility to type 1 diabetes consists of multiple components both in humans and non‐obese diabetic (NOD) mouse. In the NOD mouse, Idd16 has been mapped to the region adjacent to, but distinct from Idd1 in the MHC class II region. Establishment of subcongenic NOD.CTS‐H2 lines that possess the same MHC class II as the NOD mouse but non‐NOD‐derived chromosomal region in its adjacent regions, would facilitate further narrowing down of the localization of Idd16.
Long‐Term Prevention of Diabetes and Marked Suppression of Insulin Autoantibodies and Insulitis in Mice Lacking Native Insulin B9–23 Sequence
Authors: NAKAYAMA M. , BABAYA N. , MIAO D. , GIANANI R. , LIU E. , ELLIOTT J.F. , EISENBARTH G.S.
Published: November 2006

Abstract:  We analyzed double native insulin gene knockout NOD mice with a mutated (B16:alanine) proinsulin transgene at multiple ages for the development of insulin autoantibodies, insulitis, and diabetes. In contrast to mice with at least one copy of a native insulin gene that expressed insulin antibodies, only 2 out of 21 (10%) double native insulin gene knockout mice with a mutated insulin transgene developed insulin autoantibodies. Of 21 double insulin knockout mice sacrificed between 10 to 48 weeks of age, only 5 showed minimal insulitis versus 100% of wild‐type NOD and more than 90% of insulin 1 knockout mice. Consistent with robust suppression of insulin autoantibodies and insulitis, no double insulin knockout mice developed diabetes. In that the B9–23 peptide with B16A is an altered peptide ligand inducing Th2 responses, we analyzed transfer of splenocytes into NOD.SCID mice. There was no evidence for regulatory T cells able to inhibit transfer of diabetes by diabetogenic NOD splenocytes. Insulin peptide B9–23 is likely a crucial target for initiation of islet autoimmunity and further mutation of the sequence will be tested to attempt to eliminate all anti‐islet autoimmunity.
Peptide‐Pulsed Immature Dendritic Cells Reduce Response to β Cell Target Antigens and Protect NOD Recipients from Type I Diabetes
Authors: LO JEANNETTE , PENG RUI HUA , BARKER TOLGA , XIA CHANG‐QING , CLARE‐SALZLER MICHAEL J.
Published: November 2006

Abstract:  Our previous work demonstrated peptide‐pulsed mature myeloid dendritic cells (DC) presenting β cell antigens induce tolerance. Here we determine whether immature DC (iDC) presenting dominant (insulin β9–23 chain, proinsulin C19–A3) or ignored (glutamic acid decarboxylase 6578‐97) antigen determinants promote tolerance. Nonobese diabetic (NOD) mice were given injections of either unpulsed or peptide‐pulsed myeloid iDC beginning at 9 weeks of age for 3 consecutive weeks. Diabetes incidence in recipients of unpulsed iDC was comparable to unmanipulated animals (∼80%), whereas GAD6578–97 pulsed iDC recipients were protected from the disease (P= 0.05). We also analyzed splenic T cell proliferation responses to the panel of studied peptides in diabetic and nondiabetic recipients. When stimulated with insulin or proinsulin peptide, nondiabetic mice receiving the peptide‐pulsed iDC had a 21‐ to 31‐fold or 3.9‐ to 9.0‐fold reduction in T cell response, respectively, as compared to the response of diabetic unpulsed recipients. However, only a 2.6‐ to 3.1‐fold reduction in response to β chain peptide, and a 1.5‐ to 3.4‐fold reduction in proinsulin response were observed in diabetic mice receiving peptide‐pulsed iDC. The reduction was not specific to the immunizing peptide, as reduced proliferation was observed to other diabetes‐target peptides. We conclude that protective iDC‐based therapies require target antigen presentation, and ignored determinants may be preferable perhaps due to an available naïve T cell repertoire. In addition, iDC presenting peptides induce a nonspecific reduction in T cell responses to β cell antigens, possibly through the induction of regulatory T cells.
New Members of the Interleukin‐12 Family of Cytokines: IL‐23 and IL‐27 Modulate Autoimmune Diabetes
Authors: MENSAH‐BROWN E.P.K. , SHAHIN A. , AL‐SHAMSI M. , LUKIC M.L.
Published: November 2006

Abstract:  Multiple low doses of streptozotocin (5 × 40 mg/kg) given to susceptible male C57BL6 mice induced delayed and sustained hyperglycemia accompanied by body weight loss, mononuclear cell infiltration in the islet, and apoptosis of β cells. Shorter regimes (4 × 40 mg/kg) did not have such effect. Administration of IL‐23 at a dose of 400 ng/mL for 10 consecutive days concomitantly
with this subdiabetogenic regimen of STZ, however, induced significant hyperglycemia, weight loss, and mononuclear cellular infiltration. The same regimen of IL‐27 in duced milder effect on glycemia and no weight loss inspite of a massive peri‐islet and intra‐islet infiltration of mononuclear cells. The molecular mechanisms underlying the actions of these cytokines on diabetogenesis is under study.
In Vitro TNF‐α and IL‐6 Production by Adherent Peripheral Blood Mononuclear Cells Obtained from Type 1 and Type 2 Diabetic Patients Evaluated according to the Metabolic Control
Authors: FOSS‐FREITAS MARIA CRISTINA , FOSS NORMA TIRABOSCHI , DONADI EDUARDO ANTONIO , FOSS MILTON CESAR
Published: November 2006

Abstract:  Tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) levels were evaluated in lipopolysaccharide (LPS)‐stimulated cell cultured monocytes obtained from 24 type 1 and type 2 diabetic patients presenting inadequate (IN) or adequate (AD) metabolic control, and in 21 healthy individuals paired to patients for sex and age. The TNF‐α levels in stimulated cultures of diabetic patients were similar to healthy individuals, and type 1 diabetic patients showed increased IL‐6 supernatant levels. The tendency toward increased TNF‐α and IL‐6 levels was observed with metabolic control of type 1 and type 2 diabetic patients, suggesting that the control of diabetes improves the capacity of activation and maintenance of the proinflammatory immune response.
T Cell Immunity to Glutamic Acid Decarboxylase in Fulminant Type 1 Diabetes without Significant Elevation of Serum Amylase
Authors: AOKI KANEMI , TANIYAMA MATSUO , NAGAYAMA CHIEKO , OIKAWA YOICHI , SHIMADA AKIRA
Published: November 2006

Abstract:  We encountered three patients with fulminant type 1 diabetes whose serum amylase levels were not elevated and evaluated their immunological characteristics. Although all three patients had no antibodies to islet antigens including glutamic acid decarboxylase (GAD), GAD‐reactive T lymphocytes were detected in two patients. Combined with the findings that human leukocyte antigen (HLA) class II haplotype associated with fulminant type 1 diabetes is the same as that of autoimmune type 1 diabetes, an immune process similar to autoimmune type 1 diabetes may be involved in at least a part of fulminant type 1 diabetes.
Expression Levels of CXC Chemokine Receptors 3 Are Associated with Clinical Phenotype of Type 1 Diabetes
Authors: YAMADA SATORU , OIKAWA YOICHI , SAKAI GEN , ATSUMI YOSHIHITO , MARUYAMA TARO , SHIMADA AKIRA
Published: November 2006

Abstract:  Type 1 diabetes is recognized as one of T helper 1 cell (Th1)‐mediated diseases. The purpose of this article was to investigate the expression levels of CXC chemokine receptor 3 (CXCR3) and CC chemokine receptor 5 (CCR5) on CD4 T cells as Th1 markers in Japanese patients with type 1 diabetes and control subjects. A total of 72 patients with type 1 diabetes and 24 healthy subjects were enrolled. Their peripheral mononuclear cells were obtained and stained with anti‐CXCR3, anti‐CCR5, and anti‐CD4 monoclonal antibodies. Flow‐cytometric analysis was performed and patients were classified according to their onset pattern as fulminant, typical, or slow onset. Statistical analysis was performed using ANOVA. CXCR3 expression on CD4 T cells in patients with a fulminant pattern of onset was significantly lower than that in the other groups, and that in patients with a typical pattern of onset was significantly higher than that in the other groups. CCR5 expression on CD4 T cells was not different among the three clinical phenotypes. CXCR3 expression level is associated with the onset pattern of type 1 diabetes. Further studies are needed to clarify the role of chemokines in type 1 diabetes.
Antigenic Determinants to GAD Autoantibodies in Patients With Type 1 Diabetes With and Without Autoimmune Thyroid Disease
Authors: PARK HYEWON , YU LIPING , KIM TAEWHA , CHO BOYOUN , KANG JUNGOO , PARK YONGSOO
Published: November 2006

Abstract:  Type 1 diabetes (T1D) is frequently associated with other autoimmune diseases. Most T1D patients' sera contain two distinct glutamic acid decarboxylase (GAD) antibody specificities, of which one targets an epitope region in the middle‐third of GAD65 (amino acids 221–359) and the other targets the carboxy‐third of GAD65 (amino acids 453–569). Using five chimeric GAD65/GAD67 proteins to maintain conformation‐dependent epitopes of GAD65, we compared the humoral repertoire of antibodies from 127 T1D patients with and without autoimmune thyroid diseases (ATD). Thirty‐one patients with T1D (24%) expressed antithyroid autoantibodies ATA and 22 patients (17%) had ATD in comparison to 6% of age‐matched controls having ATA. GAD65‐antibody‐positive patients much more often (28% versus 5%, P < 0.0004) had ATD. Of 66 GAD65‐autoantibody‐positive T1D patients, 34 had autoantibodies reacting with both middle and carboxy epitopes. Autoantibodies of the other 32 reacted with middle, carboxy, or other epitopes but not with both middle‐ and carboxy‐third. Those with GAD65 autoantibodies reacting with both middle‐ and carboxy‐third had less ATD. Of 22 (23%) patients with ATD, 5 compared to 29 of 47 (62%) T1D patients without ATD had GAD65 autoantibodies reacting with both middle‐ and carboxy‐third (relative risk = 0.2, P < 0.01). These results indicate that there are both similarities and differences in the humoral response to GAD65 in ATD and T1D, and expression of antibodies to middle‐ and carboxy‐third at the same time is a feature specific to T1D.
Time‐Resolved Fluorescence Imaging of Islet Cell Autoantibodies
Authors: VUORINEN PAULI , RULLI MARIS , KUUSISTO ARI , SIMELL SATU , SIMELL TUULA , VAHLBERG TERO , ILONEN JORMA , HYÖTY HEIKKI , KNIP MIKAEL , SIMELL OLLI
Published: November 2006

Abstract:  Time‐resolved fluorescence of lanthanide chelates has been widely used in bioanalytical assays. Long fluorescence time, large Stokes shift, and minute fading out of the fluorescence over years are major advantages of the lanthanides over the conventional fluorescent dyes. We have now applied time‐resolved fluorescence imaging (TRFI) also for measurement of type 1 diabetes mellitus (T1DM)‐related islet cell autoantibodies (ICA). Retaining the accuracy of conventional ICA, TRFI has over 10 times better signal‐to‐noise ratio than the conventional fluorochromes. The technology allows objective determination of fluorescence intensity with the camera and computer software, and serial dilutions for obtaining the antibody titer in autoantibody‐positive samples are unnecessary.We now describe the TRFI as a method and its application for measurement of ICA.
Frequency of CTLA‐4 Gene CT60 Polymorphism May Not Be Affected by Vitamin D Receptor Gene Bsm I Polymorphism or HLA DR9 in Autoimmune‐Related Type 1 Diabetes in the Japanese
Authors: KANAZAWA YASUHIKO , MOTOHASHI YOSHIKO , YAMADA SATORU , OIKAWA YOICHI , SHIGIHARA TOSHIKATSU , OKUBO YOSHIAKI , MARUYAMA TARO , SHIMADA AKIRA
Published: November 2006

Abstract:  One of the CTLA‐4 SNPs, +6230G>A (CT60), has recently been reported to be related to susceptibility to type 1 diabetes and autoimmune thyroid disease. We have previously reported an association between acute‐onset type 1 diabetes in Japanese and the Vitamin D receptor (VDR) gene Bsm I large B polymorphism, which is related to the Th1‐type response. Moreover, we found a significant correlation between autoimmune‐related type 1 diabetes with HLA DR9 and detection of GAD‐reactive Th1 (T helper 1)‐type cells. In the present article, we tried to clarify whether the frequency of one of the CTLA‐4 SNPs, +6230G>A (CT60), is affected by the VDR gene Bsm I polymorphism or by HLA DR9 in Japanese type 1 diabetics. The frequency of the CT60 GG genotype did not appear to be affected by either the VDR gene Bsm I large B polymorphism or HLA DR9.
No Association of TLR2 and TLR4 Polymorphisms with Type I Diabetes Mellitus in the Basque Population
Authors: SANTIN IZORTZE , BILBAO JOSE RAMON , DE NANCLARES GUIOMAR PÉREZ , CALVO BEGOÑA , CASTAÑO LUIS
Published: November 2006

Abstract:  The destruction of pancreatic β cells that occurs in type 1 diabetes mellitus (T1DM) is mediated by the immune system, and evidence has accumulated supporting the implication of innate immune mediators. Toll‐like receptors (TLRs) participate in the first line of immune defense through antigen recognition, and their ligands are mostly exogenous but can be host‐derived as well. To test the possible role of TLRs in the development of T1DM, we studied different SNPs of TLR2 (N199N, S450S, R677W, and R753Q) and TLR4 (D299G, T399I, and S400N) in Basque families with T1DM. Several positions analyzed were not polymorphic in the Basque population. Genetic association analysis failed to demonstrate any association of these polymorphisms of TLR2 and TLR4 with T1DM in our population. The differences in TLR4 haplotype transmission to affected and unaffected offspring are indicative of a possible implication of TLR4 in disease risk but differences did not reach statistical significance.
A Second Component of HLA‐Linked Susceptibility to Type 1 Diabetes Maps to Class I Region
Authors: KAWABATA YUMIKO , IKEGAMI HIROSHI , FUJISAWA TOMOMI , NOSO SHINSUKE , ASANO KATSUAKI , HIROMINE YOSHIHISA , OGIHARA TOSHIO
Published: November 2006

Abstract:  Type 1 diabetes is a polygenic disease with a major susceptibility locus, IDDM1, located in the human leukocyte antigen (HLA) region. Although class II loci, DR and DQ genes in particular, are major components of IDDM1, accumulating lines of evidence indicated that IDDM1 consists of multiple components and that non‐class II genes in addition to class II genes contribute to susceptibility to and/or age‐at‐onset of type 1 diabetes. To identify a second component of IDDM1, we investigated the association of a panel of polymorphisms in 2.2 Mb region of the HLA encompassing from class II to class I regions with type 1 diabetes. Polymorphisms types were: DRB1 and DQB1 in class II; two microsatellite markers, BAT2‐GT and TNFa in class III; and, five microsatellite markers, STR‐MICA, MIB, C1‐3‐1, C2‐4‐4, and C3‐2‐10 in class I region. A total of >200 Japanese patients and healthy control subjects were studied. Class II DRB1*0405 and DQB1*0401 were significantly associated with susceptibility to, but not with age‐at‐onset of, type 1 diabetes. C1‐3‐1, located near C locus, was significantly associated with not only susceptibility to, but also age‐at‐onset of type 1 diabetes. These data suggest that a second component of IDDM1 maps to the HLA class I region, contributing to susceptibility to as well as age‐at‐onset of type 1 diabetes.
Molecular Scanning of the Gene for Programmed Cell Death‐1 (PDCD‐1) as a Candidate for Type 1 Diabetes Susceptibility
Authors: HIROMINE YOSHIHISA , IKEGAMI HIROSHI , FUJISAWA TOMOMI , KAWABATA YUMIKO , NOSO SHINSUKE , YAMAJI KAORI , ASANO KATSUAKI , OGIHARA TOSHIO
Published: November 2006

Abstract:  Multiple genes are involved in the susceptibility to autoimmune type 1 diabetes. The immunoreceptor programmed cell death‐1 (PDCD‐1), an inhibitory costimulatory molecule regulating peripheral tolerance, was reported to play a role in the development of type 1 diabetes, making the human PDCD‐1 gene, PDCD1, as a candidate for disease susceptibility. In this article, we sequenced all 5 exons and exon–intron junctions of PDCD1 in Japanese subjects, and found 10 sequence variants. Preliminary data suggested no association of these polymorphisms with type 1 diabetes. These sequence variants are valuable for further studies to clarify contribution of PDCD1 to susceptibility to type 1 diabetes.