bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-Implantation of Si And Be in GaAs by Rapid Thermal Annealing
Authors: Yu Tan-Hua , Wang Sujane
Published: March 2011

A buried p-layer in GaAs MESFET channel is successfully formed by (Si,Be) co-implantation and rapid thermal annealing process. The annealing cycle is optimized to activate Si and Be simultaneously and to minimize the dopant redistribution for precise dopant control. As a result, more than 80% activation efficiency for both Si and Be, as well as the greatly improved doping abruptness from 85 nm/decade to 65 nm/decade are achieved. Devices are fabricated and superior performance including sharper pinchoff, an increase of RF gain by 2–3dB and a 40% decrease in backgating effect is observed.
A Two Step Rapid Thermal Annealing Process for Be Implant Activation in GaAs
Authors: Plumton D.L. , Duncan W.M. , Tran L.T.
Published: March 2011

SUMMARY ABSTRACT

A two step rapid thermal anneal (RTA) has been studied for activating Be implanted GaAs, where a short duration, high temperature step is used to electrically activate the Be followed by a longer, low temperature anneal for lattice regrowth. p-n diodes show a substantial reduction in reverse diode leakage current after the low temperature second step anneal, when compared to a single step RTA or to furnace annealing (FA). For low energy Be implants, no difference in elecrical activiation between the two step anneal is observed. Raman studies demonstrate that residual substrate impurities and high Be concentrations inhibit restoration of single crystal lattice characteristics after RTA. Lattice quality is shown not to limit diode characteristics in the RTA material.
Rapid Thermal Annealing of Low Temperature Silicon Dioxide Films
Authors: Fitch J.T. , Lucovsky G.
Published: March 2011

This paper discusses the local atomic structure in silicon dioxide films formed by the oxidation of silicon in dry oxygen in a temperature range between 850 and 1150°C. The films grown at 850°C were subjected to rapid thermal annealing (RTA)at temperatures between 800 and 1200°C and for periods of time ranging from 1 to 100 seconds. The local atomic structure has been studied via infrared (IR) spectroscopy and ellipsometry. We discuss the temperature dependence (with respect to both oxidation temperature, and annealing temperature [and time]) of the frequency, v, and linewidth, δv, of the Si-O-Si bond stretching vibration, and the index of refraction, n, at 632.8 nm. We make comparisons with silicon dioxidefilms deposited by remote plasma enhanced chemical vapor deposition (RPECVD) at temperatures between 100 and 400C and subjected to high temperature annealing (850 to 1050°C). We find that the variations in v, δv and n with growth, deposition and annealing can be understood in terms of systematic variations in the magnitude of the bond angle, 2e, at the oxygen atom bonding sites.
Oxygen Precipitation Along Individual Ion Tracks During High Dose O+ Implantation into Silicon
Authors: Maszara Witold P.
Published: March 2011

Silicon wafers with and without protective1Ahermil oxide were implanted with oxygen at 150keV with doses 1.6 – 2.0×1018 cm−2. Transmission electron microscopy (TEM) and secondary ion mass spectroscopy (SIMS) were used to study the top silicon layer remaining above the implanted buried oxide. regular array of spheroidal voids filled with oxygen gas was observed only in the samples that were not protected by the oxide. The voids were aligned into individual columns whose crystallographic orientation with respect to the host silicon lattice matched the direction of the implantation. The origin and the kinetics of their formation are discussed.
Channeling Studies of Ion-Implantation Damage in Titanium Dioxide
Authors: Stoffel N. G. , Hart D. L.
Published: March 2011

Rutherford backscattering in the channeling alignment was used to characterize the damage produced in rutile TiO2 by oxygen ion implantation at energies of 200 and 400 keV. Backscattering g{om the dajnaged layer increases sublinearly with ion dose above 4×1015 ions/cm2. Complete amorphization was not achieved even for much higher doses and implant temperatures well below room temperature, and remnants of the original crystal lattice remain in the damaged layer. Substantial defect annealing occurs at 450 C, and essentially complete lattice recovery is observed at 750 C when the annealing takes place in a reducing environment. In an oxidizing ambient, higher annealing temperatures are required to achieve the same degree of crystal regrowth, and dechanneling actually increases at lower annealing temperatures, apparently due to the coalescence of point defects into extended defects. The optical properties of the implanted layer were also probed by ellipsometry.
Ion Induced Mixing of AlGaAs/GaAs Superlattices
Authors: Venkatesan T. , Schwarz S. A. , Mei P. , Yoon H. W.
Published: March 2011

Subsequent to the implantation of certain ions, the thermal stability of AlGaAs/GaAs superlattices can be reduced, enabling mixing of the layers at temperatures where they would otherwise be stable. The mixed layers have intermediate alloy composition and are of good crystalline quality. As a result this process is of great value in device fabrication where a high degree of vertical and lateral bandgap control is desirable. This paper reviews our work in understanding the mechanism of diffusion, its dependence on varilous process parameters, and potential applications in device fabrication.
Mechanism of Interdiffusion in Hg1-XXxTe/CdTe Superlattices (X = Cd, Mn, AND Zn)
Authors: Staudenmann J.-L. , Knox R. D. , Faurie J.-P.
Published: March 2011

The interdiffusion mechanism in Hg(l-x)X(x)Te/CdTe superlattices where X is Cd, Mn, or Zn can be deduced from the magnitude of the interdiffusion activation energy. By comparing in-situ x-ray diffraction measurements (our work) with results from Tang and Stevenson (J. Vac. Sci. Technol. AS, 1987), it is found that anionic and cationic Frenkel pairs represent the most likely interdiffusion mechanism in Hg(l-x)X(x)Te/CdTe superlattices. This model mixes vacancies and interstitials, as well as maintaining the conduction type and the electronic mobility. It is further shown that interdiffusion sets in as soon as the growth starts.
The Influence of Dose Rate on the Formation of CrSi2 by Ion Mixing
Authors: Kim S.-J. , Jamieson D. N. , Nicolet M-A. , Averback R. S.
Published: March 2011

The relationship between growth rate of CrSi2 and dose rate during Xe ion irradiation at 500K is investigated. Dose raies difffering by up to a factor of 40 have been utilized to study the relationship. For a fixed total dose, a lower dose rate results in a thicker silicide layer compound to a higher dose rate. The results are explained from radiation-enhanced diffusion theory.
Control of Al Orientation on Si(100) Substrate Using a Partially Ionized Beam
Authors: Choi C.-H. , Ramanarayanan R. , Mei S.-N. , Lu T.-M.
Published: March 2011

We report an investigation of Al films deposited on Si(100) surfaces by a partially ionized beam. By controlling the Al ion to atom ratio in the beam and the bias potential applied to the substrate, two different orientations, namely, the Al(110) and the Al(111) faces, can be formed on the Si(100) substrate.
Properties and Effects of Laser-Induced Plasma During Evaporative Deposition of Thin Films
Authors: Sankur H. , Denatale J. , Gunning W. J.
Published: March 2011

The properties of plasmas generated by the interaction of a pulsed CO2 laser with several solid evaporation targets were studied and the films deposited from such plasmas were characterized. A large flux (˜ 1014/cm2/s) of ions at high velocities (2 − 10 × 106 cm/s) was measured in these plasmas. ZrO2 thin films deposited by laser-assisted evaporation on room temperature substrates had crystalline-oriented structures. Low optical absorption and high refractive index values (2.15 at 632.8 nm) indicated the stoichiometric and dense nature of these films.
Preparation of Aluminum Nitride and Oxynitride Thin Films by Ion-Assisted Deposition
Authors: Targove J. D. , Lingg L J. , Lehan J. P. , Hwangbo C. K. , Macleod H. A. , Leavitt J. A. , Mcintyre L. C.
Published: March 2011

Aluminum nitride thin films have been deposited by ion-assisted deposition. Aluminum was electron-beam evaporated onto substrates with simultaneous nitrogen ion bombardment. Rutherford backscattering spectrometry showed that nitrogen-to-aluminum ratios of one or greater could be achieved with sufficient nitrogen ion fluxes. This excess nitrogen apparently degrades the optical properties of the films in the visible. Annealing at 500°C improves the optical properties drastically at the expense of a slight oxygen diffusion into the films. Finally, aluminum oxynitride films were deposited by adding an oxygen backfill to the vacuum chamber during deposition. These films had very similar optical properties to the annealed nitride films.
A Study of Boron Implanted Silicon
Authors: Chang P.-H. , Liu H.-Y. , Anthony J. M.
Published: March 2011

Single crystal <100> Silicon wafers implanted by 1×1016/cm2 boron ions at 30, 80, or 130 KeV are studied. The through thickness strain distribution in the wafer is found to reverse from tension in the as-implanted condition to compression after annealing for 20 minutes at 900°C. The 30 KeV implant generates a partially amorphized region under the wafer surface. Boron diffuses out of this region and accumulates at greater depth during annealing. Higher energy implants do not generate such an amorphous region and many long rod-like defects develop under a band of dislocation loops during annealing. Enhanced boron diffusion was observed at the tail of the boron profile at all three energies.
Limits on the Accuracy of Stoichiometry Determined by Rutherford Backscattering Using Computer Peak Fitting.
Authors: Mcintyre L. C. , Ashbaugh M. D. , Leavitt J. A.
Published: March 2011

Rutherford Backscattering Spectrometry (RBS) using MeV ions is capable of routinely measuring absolute atomic areal densities to an accuracy of about 3% and relative areal densities to a fraction of 1% if the elastic scattering peaks from different elements do not overlap. The accuracy of areal density measurements can be seriously reduced in cases where the sample thickness is large enough to cause overlapping peaks. We report here an investigation of the use of standard computer fitting techniques to analyze overlapping peaks in elastic scattering spectra and its effect on the accuracy of the final results of an RBS analysis.
Adhesion of Reactive Ion Implanted Copper Films on Al2O3 and SiO2
Authors: Madakson P. B. , Baglin J. E. E.
Published: March 2011

Implantation of reactive ions at the Cu-Al2O3 or Cu-SiO2 interface has been explored as a means of producing adhesion of thin copper films on these otherwise inert substrates. The process may promote complex chemical bonding at the interface due to the presence of a reactive implanted species; it may also enhance adhesion by interface layer mixing. Thin copper films (400–800Å) were deposited on fused quartz or sapphire substrates. After implantation and, in some cases, heat treatment thick Cu stripes were added to enable peel testing of adhesion strength. The reactive ion species implanted were oxygen (100 keV), or titanium (120 keV) or chromium (80 or 160 keV), to doses ranging from 1015 to 1017 ions/cm2. In each case, the energy was chosen to place the reactive implant at the interface region. For comparison with simple ion beam mixing, a similar set of samples was implanted with krypton ions at 2 MeV to doses of 1 or 3.6 × 1016 ion/cm2. The peel strength was found to be about 0.5 gm/mm for the unimplanted Cu-sapphire samples; 1.3 gm/mm for those implanted with oxygen; 18 gm/mm for those implanted with krypton; 90 gm/mm for those implanted with chromium; and more than 200 gm/mm for the titanium implanted samples. No significant increase in adhesion was achieved for the implanted Cu-quartz samples, except for the titanium implant, which gave an average peel strength of 66 gm/mm after anneal for the dose of 5 × 1016 Ti+/cm2. Studies of the interfaces and of the peeled surfaces were made, using RBS. Changes in both chemical bonding and interface morphology appear to contribute to the phenomena of enhanced adhesion.
Suppression of the Uranium-Hydrogen Reaction using High-Dose Carbon Implantation
Authors: Musket R. G.
Published: March 2011

We have previously reported the delay and reduction of the hydriding of uranium by implantation of oxygen. The reduced hydriding was attributed to the presence of the uranium oxide layer created near room temperature. In this paper we present results for the layers formed by implantation of 80 keV C+ to a dose of 8E17 C/cm2. The carbide layers formed were characterized by Auger electron spectroscopy, Rutherford backscattering, and glancing angle x-ray diffraction. Hydriding properties of both nonimplanted and implanted uranium were measured for 76 Torr hydrogen at 130°C. The implanted specimens had significantly longer incubation times for the start of the reaction after exposure to hydrogen and less area participating in the reaction.
Atomic Profiles of High Energy (MeV) Si Implanted into GaAs
Authors: Thompson Phillip E. , Wilson Robert G. , Ingram David C. , Pronko Peter P.
Published: March 2011

High energy Si implantation into GaAs is of interest for the fabrication of fully implanted monolithic microwave integrated circuits. 30Si has been implanted into LEC GaAs at energies of 1, 2, 4, and 6 MeV. We have measured atomic concentration profiles using SIMS and carrier concentration profiles using an electrolytic CV procedure. Theoretical atomic profiles have been calculated using TRIM-86. Excellent SIMS dynamic range and low background (<1014/cm3) was achieved for the profiles by the use of 30Si. The range statistics and profile shape factors: Rm, Rp, ΔRp, skewness (Y1), kurtosis (B2), and maximum Si density (Nmax) have been determined from the SIMS data by applying a Pearson IV computer fitting routine. The first two moments (Rp and ΔRp) were also obtained from the carrier profiles and the theoretical profiles. The range and standard deviation obtained from each profile have a maximum difference of only 15%, and the difference is usually less than 10%. This is less than the mutual experimental uncertainty of 17%. The samples were activated using a furnace anneal (800°C, 15 min) with a Si3N4 cap and using rapid thermal anneal (1000°C, 10s) with and without a Si3N4 cap. No redistribution of Si was observed for any of the anneal conditions within experimental error.
The Creation and Annealing of Heavy Ion Damage in Silicon
Authors: Howe L. M. , Rainville M. H.
Published: March 2011

High resolution transmission electron microscopy techniques have been used to obtain information on the contrast, spatial distribution, size and annealing behaviour of the damaged regions produced within individual collision cascades by heavy ion (As, Sb and Bi) bombardment (10–120 KeV) of silicon with 1.0 × 1011 – 6.0 × 1011 ions cm−2. The fraction of the theoretical cascade volume occupied by a heavily damaged region steadily increased as the average deposited energy density within the cascade increased. At high energy densities, the visible damage produced in the main cascade consisted of a single, isolated damaged region. With decreasing values of (i.e. increasing ion implant energies), there was an increasing tendency for multiple damaged regions to be produced within the main cascade.
TBX22 Mutation Associated with Cleft Lip/Palate, Hypodontia, and Limb Anomaly
Authors: Kaewkhampa Arunee , Jotikasthira Dhirawat , Malaivijitnond Sutti , Kantaputra Piranit
Published: March 2011

Mutations in TBX22 are known causes of cleft palate with/without ankyloglossia. We identified a hemizygous missense C.452G>T (p.Arg151Leu) mutation in a Thai boy who had unilateral complete cleft lip and palate, agenesis of a maxillary second premolar, ankyloglossia, hypoplastic carpal bones, and hypoplastic right thumb. Our study has demonstrated that TBX22 mutation is associated not only with cleft palate and ankyloglossia, but also cleft lip and palate and tooth agenesis. Phenotypic variability caused by a single nucleotide substitution is clearly demonstrated.
Role of Postoperative Radiotherapy in Resected Non-Small Cell Lung Cancer: A Reassessment Based on New Data
Authors: Le Péchoux Cécile
Published: March 2011

Learning Objectives

After completing this course, the reader will be able to: Identify patients with non-small cell lung cancer who may benefit from postoperative radiotherapy based upon current evidence.Summarize the results of analyses of both older and more recent data regarding postoperative radiotherapy in NSCLC patients.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

In completely resected non-small cell lung cancer (NSCLC) patients with pathologically involved mediastinal lymph nodes (N2), administration of adjuvant platinum-based chemotherapy is now considered the standard of care, based on level 1 evidence. The role of postoperative radiation therapy (PORT) in this group of patients remains controversial. The PORT meta-analysis published in 1998 concluded that adjuvant radiotherapy was detrimental to patients with early-stage completely resected NSCLC, but that the role of PORT in the treatment of tumors with N2 involvement was unclear, and that further research was warranted. Recent retrospective and nonrandomized studies, as well as subgroup analyses of recent randomized trials evaluating adjuvant chemotherapy, provide evidence of the possible benefit of PORT in patients with mediastinal nodal involvement. The role of PORT is also a valid question in patients with proven N2 disease who have undergone only induction chemotherapy followed by surgery, because the local recurrence rate for such patients varies in the range of 20%–60%. Based on the currently available data, PORT should be discussed for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy. There is a need for new randomized evidence to evaluate PORT using the modern three-dimensional conformal radiation technique, with attention paid to reducing the risk for, particularly, pulmonary and cardiac toxicity. A new large multi-institutional randomized trial evaluating PORT in this patient population is needed and now under way.
Tobacco Harm Reduction and the Evolution of Nicotine Dependence
Authors: Parascandola Mark
Published: March 2011

In recent years, a renewed debate has developed around the potential for modified tobacco products to play a role in reducing tobacco-related harm. During the 1960s and 1970s medical experts recommended to smokers who could not quit that they switch to cigarettes with lower tar and nicotine content. At the time, survey data suggested that smokers who switched did not compensate for the reduction in nicotine by increasing their intake. However, public health scientists were hindered in their ability to evaluate the population impact of the reduced tar strategy by a limited understanding of nicotine addiction. Smoking dependence was seen as primarily psychological and social, rather than pharmacological or biological, until the late 1970s, when addiction researchers began to apply experimental techniques from other forms of drug abuse to study smoking behavior. This history has important lessons for current discussions about tobacco harm reduction and regulation of nicotine delivery.
A Nationwide Analysis of US Racial/Ethnic Disparities in Smoking Behaviors, Smoking Cessation, and Cessation-Related Factors
Authors: Trinidad Dennis R. , Pérez-Stable Eliseo J. , White Martha M. , Emery Sherry L. , Messer Karen
Published: March 2011

Objectives. We used nationally representative data to examine racial/ethnic disparities in smoking behaviors, smoking cessation, and factors associated with cessation among US adults.

Methods. We analyzed data on adults aged 20 to 64 years from the 2003 Tobacco Use Supplement to the Current Population Survey, and we examined associations by fitting adjusted logistic regression models to the data.

Results. Compared with non-Hispanic Whites, smaller proportions of African Americans, Asian Americans/Pacific Islanders, and Hispanics/Latinos had ever smoked. Significantly fewer African Americans reported long-term quitting. Racial/ethnic minorities were more likely to be light and intermittent smokers and less likely to smoke within 30 minutes of waking. Adjusted models revealed that racial/ethnic minorities were not less likely to receive advice from health professionals to quit smoking, but they were less likely to use nicotine replacement therapy.

Conclusions. Specific needs and ideal program focuses for cessation may vary across racial/ethnic groups, such that approaches tailored by race/ethnicity might be optimal. Traditional conceptualizations of cigarette addiction and the quitting process may need to be revised for racial/ethnic minority smokers.
Interventions to Increase Physical Activity Among Healthy Adults: Meta-Analysis of Outcomes
Authors: Conn Vicki S. , Hafdahl Adam R. , Mehr David R.
Published: March 2011

Objectives. We conducted a meta-analysis summarizing the effects of interventions designed to increase physical activity among healthy adults.

Methods. Our comprehensive searches located 358 reports eligible for inclusion. We used random-effects analyses to synthesize data, and we used meta-analytic analogues of regression and analysis of variance to examine potential moderator variables. We also explored moderator variable robustness and publication bias.

Results. We computed meta-analytic results from studies comprising 99 011 participants. The overall mean effect size for comparisons of treatment groups versus control groups was 0.19 (higher mean for treatment participants than for control participants). This effect size is consistent with a mean difference of 496 ambulatory steps per day between treatment and control participants. Exploratory moderator analyses suggested that the characteristics of the most effective interventions were behavioral interventions instead of cognitive interventions, face-to-face delivery versus mediated interventions (e.g., via telephone or mail), and targeting individuals instead of communities. Participant characteristics were unrelated to physical activity effect sizes. Substantial between-studies heterogeneity remained beyond individual moderators.

Conclusions. Interventions designed to increase physical activity were modestly effective. Interventions to increase activity should emphasize behavioral strategies over cognitive strategies.
The Association Between Social Factors and Physical Activity Among Low-Income Adults Living in Public Housing
Authors: Shelton Rachel C. , McNeill Lorna H. , Puleo Elaine , Wolin Kathleen Y. , Emmons Karen M. , Bennett Gary G.
Published: March 2011

Objectives. We sought to examine the association between structural, functional, and normative social factors and physical activity among urban, low-income, racially/ethnically diverse adults.

Methods. We conducted a baseline cross-sectional survey among residents of 12 low-income housing communities in metropolitan Boston, Massachusetts. Participants were also asked to wear a pedometer for 5 days. We analyzed complete data from 1112 residents (weighted n = 1635).

Results. Residents with smaller social networks were significantly less physically active than were residents with larger social networks (b = −1503.7; P = .01) and residents with conflicting demands were more active than were residents with none (b = 601.6; P = .01), when we controlled for employment status, gender, poverty level, current health status, age, and perceived safety. Social networks were most strongly associated with physical activity among Hispanics and younger residents (aged 18–35 years).

Conclusions. These findings indicate that social factors, including social networks and role-related conflicting demands, may be important drivers of physical activity among low-income populations. Researchers and practitioners should consider social factors in developing multilevel physical activity interventions for this population.
Prevalence of Trial of Snus Products Among Adult Smokers
Authors: Biener Lois , McCausland Kristen , Curry Laurel , Cullen Jennifer
Published: March 2011

A 2008 survey assessed the proportion of smokers in 8 geographic areas who reported trying snus. In test markets, 10% of smokers had tried snus in the past year. Among young adult men, the trial rate was 29%. Trial was more likely among Whites than among minorities, among respondents with lower education than among those with higher education, and among those without immediate plans to quit smoking than among those intending to quit in the next 30 days. The association between trial and low cessation motivation is an important target for research.
Concerns of Newborn Blood Screening Advisory Committee Members Regarding Storage and Use of Residual Newborn Screening Blood Spots
Authors: Rothwell Erin W. , Anderson Rebecca A. , Burbank Matthew J. , Goldenberg Aaron J. , Lewis Michelle Huckaby , Stark Louisa A. , Wong Bob , Botkin Jeffrey R.
Published: March 2011

Objectives. We assessed attitudes and opinions of members of newborn blood screening (NBS) advisory committees regarding the storage and secondary research use of residual specimens from NBS.

Methods. We conducted focus groups in 2008 and 2009 with NBS advisory committees (4 focus groups; n = 39 participants) in the Mountain States region (i.e., AZ, CO, MT, NM, NV, TX, UT, and WY).

Results. Participants identified several challenges to implementing policies for storage of and research on residual newborn blood specimens. Themes that emerged from the data were public health relevancy; improvement of parental knowledge; impact of enhanced parental involvement; concerns over ownership, privacy, and confidentiality; identification of secondary research uses; and role of advisory committees.

Conclusions. Participants indicated that secondary uses of residual specimens entailed opportunities for improvements in NBS programs but also carried significant risks for their programs. Addressing concerns from stakeholders will be necessary for state-level adoption of national recommendations.
Investigation of EHD-Enhanced Water Evaporation and a Novel Empirical Model
Authors: Zheng De-Jiang , Cheng Yong-Qiang , Liu Hong-Jiang , Li Li-Te
Published: March 2011

This paper investigates the relationship between the enhanced evaporation rate by electric field, applied voltage (U) and electrode gap (d) in electrohydrodynamics-enhanced water evaporation. The electric fields produced by a single point-to-plane electrode configuration are used. In our experiments, the enhanced evaporation rate by electric field has shown increasing linearly with the U/d ratio. As regard the evaporation rate distribution on the plane electrode, the maximum evaporation rate is observed at the center of the plane (i.e., directly under the point electrode), and significantly decreased while the radial distance (i.e., radial distance from the point electrode centerline) increases. The evaporation rate is inversely proportional to the radial distance. A novel empirical model based on the dependence relation between the evaporation rate, U/d ratio and radial distance was developed. The model and the experimental results agree well.
Unitization of Spatially Connected Renewable Resources
Authors: Kaffine Daniel T , Costello Christopher
Published: March 2011

Spatial connectivity of renewable resources induces a spatial externality in extraction. We explore the consequences of decentralized spatial property rights in the presence of spatial externalities. We generalize the notion of unitization—developed to enhance cooperative extraction of oil and gas fields—and apply it to renewable resources which face a similar spatial commons problem. We find that unitizing a common pool renewable resource can yield first-best outcomes even when participation is voluntary, provided profit sharing rules can vary by participant.
Permanent Neonatal Diabetes and Enteric Anendocrinosis Associated With Biallelic Mutations in NEUROG3
Authors: Rubio-Cabezas Oscar , Jensen Jan N. , Hodgson Maria I. , Codner Ethel , Ellard Sian , Serup Palle , Hattersley Andrew T.
Published: March 2011

OBJECTIVE

NEUROG3 plays a central role in the development of both pancreatic islets and enteroendocrine cells. Homozygous hypomorphic missense mutations in NEUROG3 have been recently associated with a rare form of congenital malabsorptive diarrhea secondary to enteroendocrine cell dysgenesis. Interestingly, the patients did not develop neonatal diabetes but childhood-onset diabetes. We hypothesized that null mutations in NEUROG3 might be responsible for the disease in a patient with permanent neonatal diabetes and severe congenital malabsorptive diarrhea.

RESEARCH DESIGN AND METHODS

The single coding exon of NEUROG3 was amplified and sequenced from genomic DNA. The mutant protein isoforms were functionally characterized by measuring their ability to bind to an E-box element in the NEUROD1 promoter in vitro and to induce ectopic endocrine cell formation and cell delamination after in ovo chicken endoderm electroporation.

RESULTS

Two different heterozygous point mutations in NEUROG3 were identified in the proband [c.82G>T (p.E28X) and c.404T>C (p.L135P)], each being inherited from an unaffected parent. Both in vitro and in vivo functional studies indicated that the mutant isoforms are biologically inactive. In keeping with this, no enteroendocrine cells were detected in intestinal biopsy samples from the patient.

CONCLUSIONS

Severe deficiency of neurogenin 3 causes a rare novel subtype of permanent neonatal diabetes. This finding confirms the essential role of NEUROG3 in islet development and function in humans.
Updated Genetic Score Based on 34 Confirmed Type 2 Diabetes Loci Is Associated With Diabetes Incidence and Regression to Normoglycemia in the Diabetes Prevention Program
Authors: Hivert Marie-France , Jablonski Kathleen A. , Perreault Leigh , Saxena Richa , McAteer Jarred B. , Franks Paul W. , Hamman Richard F. , Kahn Steven E. , Haffner Steven ,   the DIAGRAM Consortium, Meigs James B. , Altshuler David , Knowler William C. , Florez Jose C. ,   for the Diabetes Prevention Program Research Group
Published: March 2011

OBJECTIVE

Over 30 loci have been associated with risk of type 2 diabetes at genome-wide statistical significance. Genetic risk scores (GRSs) developed from these loci predict diabetes in the general population. We tested if a GRS based on an updated list of 34 type 2 diabetes–associated loci predicted progression to diabetes or regression toward normal glucose regulation (NGR) in the Diabetes Prevention Program (DPP).

RESEARCH DESIGN AND METHODS

We genotyped 34 type 2 diabetes–associated variants in 2,843 DPP participants at high risk of type 2 diabetes from five ethnic groups representative of the U.S. population, who had been randomized to placebo, metformin, or lifestyle intervention. We built a GRS by weighting each risk allele by its reported effect size on type 2 diabetes risk and summing these values. We tested its ability to predict diabetes incidence or regression to NGR in models adjusted for age, sex, ethnicity, waist circumference, and treatment assignment.

RESULTS

In multivariate-adjusted models, the GRS was significantly associated with increased risk of progression to diabetes (hazard ratio [HR] = 1.02 per risk allele [95% CI 1.00–1.05]; P = 0.03) and a lower probability of regression to NGR (HR = 0.95 per risk allele [95% CI 0.93–0.98]; P < 0.0001). At baseline, a higher GRS was associated with a lower insulinogenic index (P < 0.001), confirming an impairment in β-cell function. We detected no significant interaction between GRS and treatment, but the lifestyle intervention was effective in the highest quartile of GRS (P < 0.0001).

CONCLUSIONS

A high GRS is associated with increased risk of developing diabetes and lower probability of returning to NGR in high-risk individuals, but a lifestyle intervention attenuates this risk.
Bimodal Effect on Pancreatic β-Cells of Secretory Products From Normal or Insulin-Resistant Human Skeletal Muscle
Authors: Bouzakri Karim , Plomgaard Peter , Berney Thierry , Donath Marc Y. , Pedersen Bente Karlund , Halban Philippe A.
Published: March 2011

OBJECTIVE

Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells.

RESEARCH DESIGN AND METHODS

Human skeletal muscle cells were cultured for up to 24 h with tumor necrosis factor (TNF)-α to induce insulin resistance, and mRNA expression for cytokines was analyzed and compared with controls (without TNF-α). Conditioned media were collected and candidate cytokines were measured by antibody array. Human and rat primary β-cells were used to explore the impact of exposure to conditioned media for 24 h on apoptosis, proliferation, short-term insulin secretion, and key signaling protein phosphorylation and expression.

RESULTS

Human myotubes express and release a different panel of myokines depending on their insulin sensitivity, with each panel exerting differential effects on β-cells. Conditioned medium from control myotubes increased proliferation and glucose-stimulated insulin secretion (GSIS) from primary β-cells, whereas conditioned medium from TNF-α–treated insulin-resistant myotubes (TMs) exerted detrimental effects that were either independent (increased apoptosis and decreased proliferation) or dependent on the presence of TNF-α in TM (blunted GSIS). Knockdown of β-cell mitogen-activated protein 4 kinase 4 prevented these effects. Glucagon-like peptide 1 protected β-cells against decreased proliferation and apoptosis evoked by TMs, while interleukin-1 receptor antagonist only prevented the latter.

CONCLUSIONS

Taken together, these data suggest a possible new route of communication between skeletal muscle and β-cells that is modulated by insulin resistance and could contribute to normal β-cell functional mass in healthy subjects, as well as the decrease seen in type 2 diabetes.
Validation of a Pediatric Diabetes Case Definition Using Administrative Health Data in Manitoba, Canada
Authors: Dart Allison B. , Martens Patricia J. , Sellers Elizabeth A. , Brownell Marni D. , Rigatto Claudio , Dean Heather J.
Published: March 2011

OBJECTIVE

To validate a case definition for diabetes in the pediatric age-group using administrative health data.

RESEARCH DESIGN AND METHODS

Population-based administrative data from Manitoba, Canada for the years 2004–2006 were anonymously linked to a clinical registry to evaluate the validity of algorithms based on a combination of hospital claim, outpatient physician visit, and drug use data over 1–3 years in youth 1–18 years of age. Agreement between data sources, sensitivity, specificity, negative (NPV) and positive predictive value (PPV) were evaluated for each algorithm. In addition, ascertainment rate of each data source, prevalence, and differences between subtypes of diabetes were evaluated.

RESULTS

Agreement between data sources was very good. The diabetes definition including one or more hospitalizations or two or more outpatient claims over 2 years provided a sensitivity of 94.2%, specificity of 99.9%, PPV of 81.6% and NPV of 99.9%. The addition of one or more prescription claims to the same definition over 1 year provided similar results. Case ascertainment rates of both sources were very good to excellent and the ascertainment-corrected prevalence for youth-onset diabetes for the year 2006 was 2.4 per 1,000. It was not possible to distinguish between subtypes of diabetes within the administrative database; however, this limitation could be overcome with an anonymous linkage to the clinical registry.

CONCLUSIONS

Administrative data are a valid source for the determination of pediatric diabetes prevalence that can provide important information for health care planning and evaluation.
Lifecourse Childhood Adiposity Trajectories Associated With Adolescent Insulin Resistance
Authors: Huang Rae-Chi , de Klerk Nicholas H. , Smith Anne , Kendall Garth E. , Landau Louis I. , Mori Trevor A. , Newnham John P. , Stanley Fiona J. , Oddy Wendy H. , Hands Beth , Beilin Lawrence J.
Published: March 2011

OBJECTIVE

In light of the obesity epidemic, we aimed to characterize novel childhood adiposity trajectories from birth to age 14 years and to determine their relation to adolescent insulin resistance.

RESEARCH DESIGN AND METHODS

A total of 1,197 Australian children with cardiovascular/metabolic profiling at age 14 years were studied serially from birth to age 14 years. Semiparametric mixture modeling was applied to anthropometric data over eight time points to generate adiposity trajectories of z scores (weight-for-height and BMI). Fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were compared at age 14 years between adiposity trajectories.

RESULTS

Seven adiposity trajectories were identified. Three (two rising and one chronic high adiposity) trajectories comprised 32% of the population and were associated with significantly higher fasting insulin and HOMA-IR compared with a reference trajectory group (with longitudinal adiposity z scores of approximately zero). There was a significant sex by trajectory group interaction (P < 0.001). Girls within a rising trajectory from low to moderate adiposity did not show increased insulin resistance. Maternal obesity, excessive weight gain during pregnancy, and gestational diabetes were more prevalent in the chronic high adiposity trajectory.

CONCLUSIONS

A range of childhood adiposity trajectories exist. The greatest insulin resistance at age 14 years is seen in those with increasing trajectories regardless of birth weight and in high birth weight infants whose adiposity remains high. Public health professionals should urgently target both excessive weight gain in early childhood across all birth weights and maternal obesity and excessive weight gain during pregnancy.
Randomized Trial of a Literacy-Sensitive, Culturally Tailored Diabetes Self-Management Intervention for Low-Income Latinos
Authors: Rosal Milagros C. , Ockene Ira S. , Restrepo Angela , White Mary Jo , Borg Amy , Olendzki Barbara , Scavron Jeffrey , Candib Lucy , Welch Garry , Reed George
Published: March 2011

OBJECTIVE

To test whether a theory-based, literacy, and culturally tailored self-management intervention, Latinos en Control, improves glycemic control among low-income Latinos with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 252 patients recruited from community health centers were randomized to the Latinos en Control intervention or to usual care. The primarily group-based intervention consisted of 12 weekly and 8 monthly sessions and targeted knowledge, attitudes, and self-management behaviors. The primary outcome was HbA1c. Secondary outcomes included diet, physical activity, blood glucose self-monitoring, diabetes knowledge and self-efficacy, and other physiological factors (e.g., lipids, blood pressure, and weight). Measures were collected at baseline and at 4- and 12-month follow-up. Change in outcomes over time between the groups and the association between HbA1c and possible mediators were estimated using mixed-effects models and an intention-to-treat approach.

RESULTS

A significant difference in HbA1c change between the groups was observed at 4 months (intervention −0.88 [−1.15 to −0.60] versus control −0.35 [−0.62 to 0.07], P < 0.01), although this difference decreased and lost statistical significance at 12 months (intervention −0.46 [−0.77 to −0.13] versus control −0.20 [−0.53 to 0.13], P = 0.293). The intervention resulted in significant change differences in diabetes knowledge at 12 months (P = 0.001), self-efficacy (P = 0.001), blood glucose self-monitoring (P = 0.02), and diet, including dietary quality (P = 0.01), kilocalories consumed (P < 0.001), percentage of fat (P = 0.003), and percentage of saturated fat (P = 0.04). These changes were in turn significantly associated with HbA1c change at 12 months.

CONCLUSIONS

Literacy-sensitive, culturally tailored interventions can improve diabetes control among low-income Latinos; however, strategies to sustain improvements are needed.
Iterative algorithms for variational inclusions, mixed equilibrium and fixed point problems with application to optimization problems
Authors: Yao Yonghong , Cho Yeol , Liou Yeong-Cheng
Published: March 2011

In this paper, we introduce an iterative algorithm for finding a common element of the set of solutions of a mixed equilibrium problem, the set of fixed points of a nonexpansive mapping, and the the set of solutions of a variational inclusion in a real Hilbert space. Furthermore, we prove that the proposed iterative algorithm converges strongly to a common element of the above three sets, which is a solution of a certain optimization problem related to a strongly positive bounded linear operator.
Effects of plant lectin and extracts on adhesion molecules of endothelial progenitors
Authors: Iordache Florin , Carmen Iordache , Aneta Pop , Lupu Marilena , Andrei Eugen , Buzila Cosmin , Maniu Horia
Published: March 2011

Promise of cell therapy has advanced the use of adult stem cells towards the development of novel approaches to promote regeneration of injured endothelium. The aim of this study was to stimulate endothelial progenitor cells (EPCs) with lectin isolated from Solanum tuberosum (potato) shoot and Calendula officinalis (marigold) extracts, in order to increase EPCs proliferation and gene expression of molecules with roles in chemotaxis and adhesion for a better attachment to injured vascular tissue. EPCs were differentiated from umbilical cord blood-derived mononuclear cells and characterized by light microscopy, flow cytometry, and vascular tube-like structures formation on Matrigel. Cell proliferation was determined by MTS assay, and gene expression of molecules involved in EPCs adhesion (VCAM-1, VE-cadherin, ICAM-1, PECAM-1, P-selectin) and chemotaxis was determined (CXCR4, Tie-2) by RT-PCR. For the assessment of cell motility, wound-healing assay was employed. Both potato shoot lectin and marigold extracts stimulated EPCs proliferation in a concentration dependent manner and were able to increase expression of adhesion and chemotactic molecules. Marigold flower extract proved to be more efficient. This study demonstrates the usefulness of potato lectin and marigold extracts to increase EPCs proliferation and modulate gene expression of chemotactic and adhesion molecules, which may facilitate EPCs attachment to injured endothelium.
Polymeric ionic liquid as a background electrolyte modifier enhancing the separation of inorganic anions by capillary electrophoresis
Authors: Zhou Yabin , Li Jing , Han Haifeng , Liu Xia , Jiang Shengxiang
Published: March 2011

A novel and easy method for the separation of inorganic anions by capillary electrophoresis using a polymeric ionic liquid (PIL), poly(1-vinyl-3-butylimidazolium bromide) as a background electrolyte modifier has been developed. The PIL has been proved to generate a reversed electroosmotic flow which reduces the analysis time and improves the separation significantly. Effects of the PIL concentration and buffer composition (pH and concentration) were evaluated on basis of the resolution and efficiency of the sample. Under optimum conditions, good separation of six model inorganic anions was achieved with high efficiency and excellent reproducibility within 3 min. The results obtained indicate that the combination of reversed EOF and the association between the analytes and the PIL on the capillary wall or BGE play a prominent role in the separation of anions. Therefore, the PIL presents a useful alternative for the BGE modifier in the study of inorganic anions by CE.
Synthesis, molecular characterisation, and in vivo study of platinum(IV) coordination compounds against B16 mouse melanoma tumours
Authors: Łakomska Iwona , Kaźnica Anna , Joachimiak Romana , Marszałek Andrzej , Sitkowski Jerzy , Kozerski Lech , Drewa Tomasz
Published: March 2011

A novel platinum(IV) coordination compound with 6-mercaptopurine (6-Hmp) has been synthesised and characterised by IR and NMR spectroscopy. Spectroscopic parameters indicate the presence of two chelate (S-6, N-7) monodeprotonated ligands and two chloride ions in the coordination sphere of [PtCl2(6-mp)2] · H2O (I). Two Pt(IV) coordination compounds, [PtCl2(6-mp)2] · H2O (I) and [PtCl4(dbtp)2] (II), were used in the in vivo test against B16 mouse melanoma tumours. Cytotoxic activity of compound II against the tumour cells was found to be high (LC10 = 2.6 μM, LC50 = 17.0 μM, LC90 = 58.0 μM) compared to that of cisplatin.
Antimycobacterial 3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones substituted on phenyl and benzoxazine moiety in position 6
Authors: Petrlíková Eva , Waisser Karel , Doležal Rafael , Holý Pavel , Gregor Jiří , Kuneš Jiři , Kaustová Jarmila
Published: March 2011

A series of forty-five derivatives of 3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and forty-five derivatives of 3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones was synthesised. The compounds exhibited in-vitro activity against Mycobacterium tuberculosis, M. kansasii (two strains), and M. avium. The most active derivatives were more active than isonicotinhydrazide (INH). The quantitative relationships between the structure and antimycobacterial activity were calculated. The activity against M. tuberculosis increased with the lipophilicity of the substituents.
Diseases, health status, and mortality in urban and rural environments: The case of Catholics and Lutherans in 19th-century Greater Poland
Authors: Liczbińska Grażyna
Published: March 2011

The aim of the study is to show in the mortality measures calculated for Catholics and Lutherans from 19th-century Greater Poland: 1) stratification dependent on the size of place of residence, 2) stratification dependent on religious denomination in population centres of various size. The data on mortality are drawn from Catholic and Lutheran parish death registers: from Poznań (the poor Catholic St. Margaret's Parish, the wealthy St. Mary Magdalene's Parish, and the Lutheran Holy Cross Parish), small towns such as Leszno (the Lutheran Holy Cross Parish) and Kalisz (the Catholic St. Joseph's Parish) as well as the rural Lutheran parish of Trzebosz and the Catholic parish of Dziekanowice. Stratification in the causes of death and mortality measures among Catholics and Lutherans from 19th-century Greater Poland depends on the size of their places of residence and broadly understood ecological conditions. Smaller deleterious effects of the environment were observed in the rural areas and small towns and, therefore, a relationship between death rate values and religious denominations is more visible in these than in Poznań. The cultural benefits accruing to the Lutherans and Catholics living in 19th century Poznań were insufficient to reduce the high infant death rate.
Morphometric Differences Between the Phylogeographic Lineages of the Common Hamster Cricetus Cricetus in Poland
Authors: Banaszek Agata , Ziomek Joanna , Jadwiszczak Katarzyna
Published: March 2011

Morphometric Differences Between the Phylogeographic Lineages of the Common Hamster Cricetus Cricetus in Poland

As the common hamster is endangered in the European part of its range, it is necessary to define the conservation units for successful management of natural populations. Here we describe the case of clear morphometric differentiation between phylogeographic lineages of the common hamster. The standard external measurements were taken from 209 common hamsters collected during the period 2005-2007 from the present species range in Poland. The studied populations belong to different phylogeographic lineages P3 (Polish Pannonia) and E1, and the hamsters of P3 lineage are smaller with longer feet and tails than the hamsters of E1 lineage. The phylogeographic lineages of the common hamster can be defined as evolutionary significant units (ESU) due to the significant genetic differentiation and as management units (MU) with the evidence for ecological differentiation.