bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Novel Gene for Diabetic Traits in Rats, Mice, and Humans
Authors: Tsaih Shirng-Wern , Holl Katie , Jia Shuang , Kaldunski Mary , Tschannen Michael , He Hong , Andrae Jaime Wendt , Li Shun-Hua , Stoddard Alex , Wiederhold Andrew , Parrington John , Ruas da Silva Margarida , Galione Antony , Meigs James ,   Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) Investigators, Hoffmann Raymond G , Simpson Pippa , Jacob Howard , Hessner Martin , Solberg Woods Leah C 
Published: September 2014

AbstractThe genetic basis of type 2 diabetes remains incompletely defined despite the use of multiple genetic strategies. Multiparental populations such as heterogeneous stocks (HS) facilitate gene discovery by allowing fine mapping to only a few megabases, significantly decreasing the number of potential candidate genes compared to traditional mapping strategies. In the present work, we employed expression and sequence analysis in HS rats (Rattus norvegicus) to identify Tpcn2 as a likely causal gene underlying a 3.1-Mb locus for glucose and insulin levels. Global gene expression analysis on liver identified Tpcn2 as the only gene in the region that is differentially expressed between HS rats with glucose intolerance and those with normal glucose regulation. Tpcn2 also maps as a cis-regulating expression QTL and is negatively correlated with fasting glucose levels. We used founder sequence to identify variants within this region and assessed association between 18 variants and diabetic traits by conducting a mixed-model analysis, accounting for the complex family structure of the HS. We found that two variants were significantly associated with fasting glucose levels, including a nonsynonymous coding variant within Tpcn2. Studies in Tpcn2 knockout mice demonstrated a significant decrease in fasting glucose levels and insulin response to a glucose challenge relative to those in wild-type mice. Finally, we identified variants within Tpcn2 that are associated with fasting insulin in humans. These studies indicate that Tpcn2 is a likely causal gene that may play a role in human diabetes and demonstrate the utility of multiparental populations for positionally cloning genes within complex loci.
Bayesian Modeling of Haplotype Effects in Multiparent Populations
Authors: Zhang Zhaojun , Wang Wei , Valdar William 
Published: September 2014

Abstract
A general Bayesian model, Diploffect, is described for estimating the effects of founder haplotypes at quantitative trait loci (QTL) detected in multiparental genetic populations; such populations include the Collaborative Cross (CC), Heterogeneous Socks (HS), and many others for which local genetic variation is well described by an underlying, usually probabilistically inferred, haplotype mosaic. Our aim is to provide a framework for coherent estimation of haplotype and diplotype (haplotype pair) effects that takes into account the following: uncertainty in haplotype composition for each individual; uncertainty arising from small sample sizes and infrequently observed haplotype combinations; possible effects of dominance (for noninbred subjects); genetic background; and that provides a means to incorporate data that may be incomplete or has a hierarchical structure. Using the results of a probabilistic haplotype reconstruction as prior information, we obtain posterior distributions at the QTL for both haplotype effects and haplotype composition. Two alternative computational approaches are supplied: a Markov chain Monte Carlo sampler and a procedure based on importance sampling of integrated nested Laplace approximations. Using simulations of QTL in the incipient CC (pre-CC) and Northport HS populations, we compare the accuracy of Diploffect, approximations to it, and more commonly used approaches based on Haley–Knott regression, describing trade-offs between these methods. We also estimate effects for three QTL previously identified in those populations, obtaining posterior intervals that describe how the phenotype might be affected by diplotype substitutions at the modeled locus.
High-Resolution Genetic Mapping of Complex Traits from a Combined Analysis of F2 and Advanced Intercross Mice
Authors: Parker Clarissa C , Carbonetto Peter , Sokoloff Greta , Park Yeonhee J , Abney Mark , Palmer Abraham A 
Published: September 2014

AbstractGenetic influences on anxiety disorders are well documented; however, the specific genes underlying these disorders remain largely unknown. To identify quantitative trait loci (QTL) for conditioned fear and open field behavior, we used an F2 intercross (n = 490) and a 34th-generation advanced intercross line (AIL) (n = 687) from the LG/J and SM/J inbred mouse strains. The F2 provided strong support for several QTL, but within wide chromosomal regions. The AIL yielded much narrower QTL, but the results were less statistically significant, despite the larger number of mice. Simultaneous analysis of the F2 and AIL provided strong support for QTL and within much narrower regions. We used a linear mixed-model approach, implemented in the program QTLRel, to correct for possible confounding due to familial relatedness. Because we recorded the full pedigree, we were able to empirically compare two ways of accounting for relatedness: using the pedigree to estimate kinship coefficients and using genetic marker estimates of “realized relatedness.” QTL mapping using the marker-based estimates yielded more support for QTL, but only when we excluded the chromosome being scanned from the marker-based relatedness estimates. We used a forward model selection procedure to assess evidence for multiple QTL on the same chromosome. Overall, we identified 12 significant loci for behaviors in the open field and 12 significant loci for conditioned fear behaviors. Our approach implements multiple advances to integrated analysis of F2 and AILs that provide both power and precision, while maintaining the advantages of using only two inbred strains to map QTL.
Characterizing Uncertainty in High-Density Maps from Multiparental Populations
Authors: Ahfock Daniel , Wood Ian , Stephen Stuart , Cavanagh Colin R , Huang B Emma 
Published: September 2014

Abstract
Multiparental populations are of considerable interest in high-density genetic mapping due to their increased levels of polymorphism and recombination relative to biparental populations. However, errors in map construction can have significant impact on QTL discovery in later stages of analysis, and few methods have been developed to quantify the uncertainty attached to the reported order of markers or intermarker distances. Current methods are computationally intensive or limited to assessing uncertainty only for order or distance, but not both simultaneously. We derive the asymptotic joint distribution of maximum composite likelihood estimators for intermarker distances. This approach allows us to construct hypothesis tests and confidence intervals for simultaneously assessing marker-order instability and distance uncertainty. We investigate the effects of marker density, population size, and founder distribution patterns on map confidence in multiparental populations through simulations. Using these data, we provide guidelines on sample sizes necessary to map markers at sub-centimorgan densities with high certainty. We apply these approaches to data from a bread wheat Multiparent Advanced Generation Inter-Cross (MAGIC) population genotyped using the Illumina 9K SNP chip to assess regions of uncertainty and validate them against the recently released pseudomolecule for the wheat chromosome 3B.
Electrical Properties at Grain Boundaries Influenced by Cr3+Diffusion in SnO2.ZnO.Nb2O5-Films Varistor Prepared by Electrophoresis Deposition
Authors: Lustosa Glauco M. M. M. , Costa João Paulo C. , Perazolli Leinig A. , Zaghete Maria A. 
Published: September 2014

ABSTRACTSnO2-based varistors are strong candidates to replace the ZnO-based varistors due to ordering fewer additives to improve its electrical behavior as well as by showing similar nonlinear characteristics of ZnO varistors. In this work, SnO2-nanoparticles based-varistors with addition of 1.0 %mol of ZnO and 0.05 %mol of Nb2O5were synthesized by chemical route. SnO2.ZnO.Nb2O5-films with 5 μm of thickness were obtained by electrophoretic deposition (EPD) of the nanoparticles on Si/Pt substrate from alcoholic suspension of SnO2-based powder. The sintering step was carried out in a microwave oven at 1000 °C for 40 minutes. Then, Cr3+ions were deposited on the films surface by EPD after the sintering step. Each sample was submitted to different thermal treatments to improve the varistor behavior by diffusion of ions in the samples. The films showed a nonlinear coefficient (α) greater than 9, breakdown voltage (VR) around 60 V, low leakage current (IF≈ 10-6A), height potential barrier above 0.5 eV and grain boundary resistivity upward of 107Ω.cm.
Synthesis and Characterization of NaNbO3 Mesostructure by a Microwave-Assisted Hydrothermal Method
Authors: Teixeira Guilhermina F. , Zaghete Maria Ap. , Varela José A. , Longo Elson 
Published: September 2014

ABSTRACTIn the present work, we report the synthesis and characterization of NaNbO3 particles obtained by microwave-assisted hydrothermal method from Nb2O5 and NaOH. The synthesis was made at different periods at 180 °C and 300W. The crystallization of NaNbO3 structures produced Na2Nb2O6.H2O in the intermediate phase with fiber-like morphology, and this is associated with the synthesis time. Pure orthorhombic NaNbO3 with cube-like morphology originates after synthesizing for 240 minutes. To verify the remnant polarization of particles, films were obtained by electrophoresis process and sintered at 800°C for 10 minutes in a microwave furnace. The films characterization indicated that films of niobate with fiber-like morphology present remaining polarization, and the morphology of cubes did not show remaining polarization. Considering these results, it can be concluded that the morphology implemented ferroelectric property of NaNbO3.
Fabrication of Flexible Photonic Crystal Slabs
Authors: Karrock Torben , Schmalz Julius , Nazirizadeh Yousef , Gerken Martina 
Published: September 2014

ABSTRACTTwo methods for the fabrication of flexible and stretchable photonic crystal slabs are demonstrated and compared. In both cases a periodically nanostructured polydimethylsiloxane (PDMS) membrane is used as substrate. The first method is based on oblique-angle vapor deposition of SiO as a high refractive index material onto the nanostructured membrane. The deposition is made at an angle of 45° to the surface. The grooves of the nanostructure are aligned such that shading effects cause an inhomogeneous layer thickness distribution on the surface. This supports controlled, periodic cracking of the high index layer upon stretching. In the second approach ZnO nanoparticles are spin-coated on the nanostructured PDMS membrane. Here, the membrane can be stretched and serves as a photonic crystal slab without the need of any further treatment. For both types of flexible photonic crystal slabs a shift of the guided mode resonances to longer wavelengths is observed upon stretching. For a 20% strain perpendicular to the grating grooves a resonance shift of more than 50 nm is obtained.
Experience With Afatinib in Patients With Non-Small Cell Lung Cancer Progressing After Clinical Benefit From Gefitinib and Erlotinib
Authors: Schuler Martin , Fischer Jürgen R. , Grohé Christian , Gütz Sylvia , Thomas Michael , Kimmich Martin , Schneider Claus-Peter , Laack Eckart , Märten Angela ,   for the Afatinib Compassionate Use Consortium
Published: September 2014

Abstract

Background.
Afatinib, an irreversible ErbB family blocker, demonstrated superiority to chemotherapy as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is also active in patients progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs). We report the results of a large cohort of NSCLC patients receiving afatinib within a compassionate-use program (CUP).

Patients and Methods.
Patients with advanced NSCLC progressing after one line or more of chemotherapy and one line or more of EGFR-TKI treatment with either an EGFR mutation or documented clinical benefit were enrolled. Data collection was not monitored or verified by central review. The intention of this CUP was to provide controlled preregistration access to afatinib for patients with life-threatening diseases and no other treatment option.

Results.
From May 2010 to October 2013, 573 patients (65% female; median age: 64 years [range: 28–89 years]) were enrolled, with strong participation of community oncologists. Comorbidities were allowed, including second malignancies in 11% of patients. EGFR mutation status was available in 391 patients (72%), and 83% tested mutation positive. Median time to treatment failure (TTF) of 541 patients treated with afatinib was 3.7 months (range: 0.0 to &gt;29.0 months). Median TTF was 4.0 and 2.7 months in patients with adenocarcinomas and squamous cell carcinomas, respectively, and 4.6 months in patients with EGFR-mutated NSCLC. Adverse events were generally manageable.

Conclusion.
Afatinib was able to be given in a real-world setting to heavily pretreated patients with EGFR-mutated or EGFR-TKI-sensitive NSCLC. Acknowledging the constraints of data collection in a CUP, afatinib appears to be safe and to confer some clinical benefit in this population.
Serum Adenosine Deaminase Level is High But Not Related with Disease Activity Parameters in Patients with Rheumatoid Arthritis
Authors: Demir Gülseren , Borman Pınar , Ayhan Figen , Özgün Tuba , Kaygısız Ferda , Yilmez Gulsen 
Published: September 2014

Serum adenosine deaminase (ADA) has been previously proposed to predict disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the level of serum ADA, and the relationship between ADA and disease activity markers, in a group of patients with RA.A hundred and 10 patients with a diagnosis of RA were recruited from outpatient clinic of Rheumatology Unit. Demographic properties comprising age, gender, disease duration and drugs were recorded. Disease activity based on disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) and DAS28- C reactive protein (CRP,) ESR, CRP levels, as well as pain by visual analog scale and rheumatoid factor (RF) were recorded. Serum ADA levels (IU/L) were determined in all RA patients and in 55 age and sex similar healthy control subjects.Ninety-six female and 14 male RA patients with a mean age of 54.32±11.51, and with a mean disease duration of 11.5±9.13 years were included to the study. The control group comprised of 48 female and 7 male healthy subjects. 35.5% of the patients were on methotrexate (MTX) and 64.5% of patients were on combined DMARDs or combined MTX and anti-TNF therapies. The mean serum ADA level was statistically higher in RA patients than in control subjects (27.01±10.6 IU/Lvs21.8 ±9.9 IU/L). The mean values of ESR (23.2±14.8 mm/h), CRP (1.71±1.11mg/dL), pain by VAS (37.2±27.1), DAS28-ESR (2.72±0.77), DAS28 CRP (1.37±0.5) were not correlated with ADA levels (p>0.05).Our results have shown that serum ADA levels are higher in RA patients than in controls but were not related with any of the disease activity markers. We conclude that ADA in the serum may not be a reliable biochemical marker to predict disease activity in patients with RA.
Incidence of Remission in Adults With Type 2 Diabetes: The Diabetes & Aging Study
Authors: Karter Andrew J. , Nundy Shantanu , Parker Melissa M. , Moffet Howard H. , Huang Elbert S. 
Published: September 2014

OBJECTIVE
To estimate the incidence of remission in adults with type 2 diabetes not treated with bariatric surgery and to identify variables associated with remission.

RESEARCH DESIGN AND METHODS
We quantified the incidence of diabetes remission and examined its correlates among 122,781 adults with type 2 diabetes in an integrated healthcare delivery system. Remission required the absence of ongoing drug therapy and was defined as follows: 1) partial: at least 1 year of subdiabetic hyperglycemia (hemoglobin A1c [HbA1c] level 5.7–6.4% [39–46 mmol/mol]); 2) complete: at least 1 year of normoglycemia (HbA1c level &lt;5.7% [&lt;39 mmol/mol]); and 3) prolonged: complete remission for at least 5 years.

RESULTS
The incidence density (remissions per 1,000 person-years; 95% CI) of partial, complete, or prolonged remission was 2.8 (2.6–2.9), 0.24 (0.20–0.28), and 0.04 (0.01–0.06), respectively. The 7-year cumulative incidence of partial, complete, or prolonged remission was 1.47% (1.40–1.54%), 0.14% (0.12–0.16%), and 0.007% (0.003–0.020%), respectively. The 7-year cumulative incidence of achieving any remission was 1.60% in the whole cohort (1.53–1.68%) and 4.6% in the subgroup with new-onset diabetes (&lt;2 years since diagnosis) (4.3–4.9%). After adjusting for demographic and clinical characteristics, correlates of remission included age &gt;65 years, African American race, &lt;2 years since diagnosis, baseline HbA1c level &lt;5.7% (&lt;39 mmol/mol), and no diabetes medication at baseline.

CONCLUSIONS
In community settings, remission of type 2 diabetes does occur without bariatric surgery, but it is very rare.
Permanence of Values as an Important Element of Family Life
Authors: Cudak Henryk 
Published: September 2014

Abstract
In contemporary family the roles of parents have changed. The methods of passing values and their hierarchy to children are also changed. Therefore it is important for nowadays families to have an aware educational and upbringing program, as it is the only way, through the consequent teaching of the system of values, set in new social role context it is possible for a child to achieve the coherent system of values
The Therapeutic and Educational Properties of Fairytale Therapy in the Early Stages of Children’S Development
Authors: Kuciapiński Marek Jan 
Published: September 2014

Abstract
Literature builds children’s personal resources. It not only confers knowledge, but also helps to know other ways of thinking and acting. It shows patterns of behaviour that give considerable support in emotionally difficult situation; compensates for any deficiencies; relaxes releasing a good mood. Such an approach to the role of literature shows that the influence on a child using a variety of psychological mechanisms, mainly imitation and identification plays an essential role in the therapy and prophylaxis.
Fables, fairy tales (these two concepts often used interchangeably) build a lot of bridges to the art of imagination, to other people and to each other. Therefore, knowing their role is not only interesting but also necessary. Fairy tales are therapeutic means for independent and creative way to cope with the world. They are an excellent way to build relationships between parents and children. They allow to establish a closer contact with a toddler, understand its situation, emotions and a way of looking at the world. Thus, a treatment by fairy tales is one of the best methods to reach the child’s understanding of its problems and provide support in difficult times.
The main purpose of the following article is to show how great and educational value of literature is in the life of children; how it can be used to help a child overcome his difficulties. It presents the fairy tale not only as a factor in developing imagination, raising an interest in reading, satisfying curiosity and transmitting moral values providing many emotions, but also as a therapeutic agent
Scientific Tourism, Aspects, Religious and Ethics Values
Authors: Kosiewicz Jerzy 
Published: September 2014

Abstract
The presented paper focuses primarily on the tourism activities of teaching staff at universities and other research institutions. This applies in particular to travel during which the principal purpose is, inter alia, various exploratory internships, conferences, trips as a guest professor or a visiting professor under the auspices of the Erasmus and Erasmus Mundus programs. These peregrinations require extra effort, not only with regards to teaching and research duties, but also present opportunities to confront, test and evaluate one’s own research results and outlook with new listeners in new locations in different environments. This travel especially applies to the foreign environment, a situation that presents high degrees of professional, scientific and linguistic challenges, resulting in increased contributions and activity to the specific field of science. Regardless of the workload and the difficulties of the discussed travel, such travel can also bring about much personal satisfaction: a) due to a sense of a well done job as a result of meeting expectations of the employer and the host placed on the 'messenger of science' and b) due to the pleasure associated with those tourist experiences having autotelic and pragmatic (instrumental) overtones
The Perceived Differences in Interdepartmental Communication Regarding Organisational Formalisation: a Case Study of an International Company
Authors: Pruvli Elena , Alas Ruth 
Published: September 2014

Abstract
The goal of this paper is to study differences in communication between two cultures that are believed to belong to a low-context pole and represent “old“ and “new“ European. It is achieved in the context of the German-based MNE by investigation of the perceived differences between Estonian and Bavarian-based production units. An exploratory qualitative case study with ethnographic techniques proved that the reason for dysfunctional outcomes originated in how knowledge of norms was transferred and in differences in cultural orientations. It concludes that prior to organisational learning and development activities MNE managers should get training in intercultural communication
In Situ Ablation Recession Sensor for Ablative Materials Based on Ultraminiature Thermocouples
Authors: Yee Colin , Ray Matt , Tang Felix , Wan Jonathan , Tatuaca Richard , Natali Maurizio , Koo Joseph H. 
Published: September 2014

This study involved the development of an in situ ablation sensor designed to evaluate the recession rate for an ablative thermal protection system exposed to a hyperthermal environment. Design requirements specify that the sensor be constructed using multiple thermocouples at staggered depths, drilled and mounted into carbon/carbon composite and carbon/phenolic ablatives. During erosion, the thermocouples record thermal data and then melt when the flame front approaches the thermocouples. The position of the recession front and breaking time of the thermocouple can determine the ablation rate. Earlier designs developed by the authors’ research group involved the use of 0.25-mm-diam thermocouples and electric discharge machining. Later designs used 0.5-mm-diam thermocouples using conventional microdrilling: This approach can be used in all applications in which the intrusiveness of the thermocouple embedded in the thermal protection system is not a primary requirement and allows 0.5 mm thermocouples to be used as a replacement for ultrasmall and costly 0.25 mm thermocouples.