bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exendin-4 Stimulation of Cyclin A2 in β-Cell Proliferation
Authors: Song Woo-Jin , Schreiber Weston E. , Zhong Enhong , Liu Fei-Fei , Kornfeld Benjamin D. , Wondisford Fredric E. , Hussain Mehboob A. 
Published: June 2008

OBJECTIVE—β-Cell proliferation is an important mechanism underlying β-cell mass adaptation to metabolic demands. We have examined effects, in particular those mediated through intracellular cAMP signaling, of the incretin hormone analog exendin-4 on cell cycle regulation in β-cells.
RESEARCH DESIGN AND METHODS—Changes in islet protein levels of cyclins and of two critical cell cycle regulators cyclin kinase inhibitor p27 and S-phase kinase–associated protein 2 (Skp2) were assessed in mice treated with exendin-4 and in a mouse model with specific upregulation of nuclear cAMP signaling exhibiting increased β-cell proliferation (CBP-S436A mouse). Because cyclin A2 was stimulated by cAMP, we assessed the role of cylcin A2 in cell cycle progression in Min6 and isolated islet β-cells.
RESULTS—Mice treated with exendin-4 showed increased β-cell proliferation, elevated islet protein levels of cyclin A2 with unchanged D-type cyclins, elevated PDX-1 and Skp2 levels, and reduced p27 levels. Exendin-4 stimulated cyclin A2 promoter activity via the cAMP–cAMP response element binding protein pathway. CBP-S436A islets exhibited elevated cyclin A2, reduced p27, and no changes in D-type cyclins, PDX-1, or Skp2. In cultured islets, exendin-4 increased cyclin A2 and Skp2 and reduced p27. Cyclin A2 overexpression in primary islets increased proliferation and reduced p27. In Min6 cells, cyclin A2 knockdown prevented exendin-4–stimulated proliferation. PDX-1 knockdown reduced exendin-4–stimulated cAMP synthesis and cyclin A2 transcription.
CONCLUSIONS—Cyclin A2 is required for β-cell proliferation, exendin-4 stimulates cyclin A2 expression via the cAMP pathway, and exendin-4 stimulation of cAMP requires PDX-1.
The Common P446L Polymorphism in GCKR Inversely Modulates Fasting Glucose and Triglyceride Levels and Reduces Type 2 Diabetes Risk in the DESIR Prospective General French Population
Authors: Vaxillaire Martine , Cavalcanti-Proença Christine , Dechaume Aurélie , Tichet Jean , Marre Michel , Balkau Beverley , Froguel Philippe ,   for the DESIR Study Group
Published: June 2008

OBJECTIVE— Hepatic glucokinase (GCK) is a key regulator of glucose storage and disposal in the liver, where its activity is competitively modulated, with respect to glucose, by binding to glucokinase regulatory protein (GCKR) in the presence of fructose 6-phosphate. Genome-wide association studies for type 2 diabetes identified GCKR as a potential locus for modulating triglyceride levels. We evaluated, in a general French population, the contribution of the GCKR rs1260326-P446L polymorphism to quantitative metabolic parameters and to dyslipidemia and hyperglycemia risk.
RESEARCH DESIGN AND METHODS— Genotype effects of rs1260326 were studied in 4,833 participants from the prospective DESIR (Data from an Epidemiological Study on the Insulin Resistance syndrome) cohort both at inclusion and using the measurements at follow-up.
RESULTS— The minor T-allele of rs1260326 was strongly associated with lower fasting glucose (−1.43% per T-allele; P = 8 × 10−13) and fasting insulin levels (−4.23%; P = 3 × 10−7), lower homeostasis model assessment of insulin resistance index (−5.69%; P = 1 × 10−8), and, conversely, higher triglyceride levels (3.41%; P = 1 × 10−4) during the 9-year study. These effects relate to a lower risk of hyperglycemia (odds ratio [OR] 0.79 [95% CI 0.70–0.88]; P = 4 × 10−5) and of incident cases during the study (hazard ratio [HR] 0.83 [0.74–0.95]; P = 0.005). Moreover, an additive effect of GCKR rs1260326(T) and GCK (−30G) alleles conferred lower fasting glycemia (P = 1 × 10−13), insulinemia (P = 5 × 10−6), and hyperglycemia risk (P = 1 × 10−6).
CONCLUSIONS— GCKR-L446 carriers are protected against type 2 diabetes despite higher triglyceride levels and risk of dyslipidemia, which suggests a potential molecular mechanism by which these two components of the metabolic syndrome can be dissociated.
Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1
Authors: DeAngelis Anthony M. , Heinrich Garrett , Dai Tong , Bowman Thomas A. , Patel Payal R. , Lee Sang Jun , Hong Eun-Gyoung , Jung Dae Young , Assmann Anke , Kulkarni Rohit N. , Kim Jason K. , Najjar Sonia M. 
Published: June 2008

OBJECTIVE—Liver-specific inactivation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) by a dominant-negative transgene (l-SACC1 mice) impaired insulin clearance, caused insulin resistance, and increased hepatic lipogenesis. To discern whether this phenotype reflects a physiological function of CEACAM1 rather than the effect of the dominant-negative transgene, we characterized the metabolic phenotype of mice with null mutation of the Ceacam1 gene (Cc1−/−).
RESEARCH DESIGN AND METHODS—Mice were originally generated on a mixed C57BL/6x129sv genetic background and then backcrossed 12 times onto the C57BL/6 background. More than 70 male mice of each of the Cc1−/− and wild-type Cc1+/+ groups were subjected to metabolic analyses, including insulin tolerance, hyperinsulinemic-euglycemic clamp studies, insulin secretion in response to glucose, and determination of fasting serum insulin, C-peptide, triglyceride, and free fatty acid levels.
RESULTS—Like l-SACC1, Cc1−/− mice exhibited impairment of insulin clearance and hyperinsulinemia, which caused insulin resistance beginning at 2 months of age, when the mutation was maintained on a mixed C57BL/6x129sv background, but not until 5–6 months of age on a homogeneous inbred C57BL/6 genetic background. Hyperinsulinemic-euglycemic clamp studies revealed that the inbred Cc1−/− mice developed insulin resistance primarily in liver. Despite substantial expression of CEACAM1 in pancreatic β-cells, insulin secretion in response to glucose in vivo and in isolated islets was normal in Cc1−/− mice (inbred and outbred strains).
CONCLUSIONS—Intact insulin secretion in response to glucose and impairment of insulin clearance in l-SACC1 and Cc1−/− mice suggest that the principal role of CEACAM1 in insulin action is to mediate insulin clearance in liver.
Beneficial Effects of Insulin on Glycemic Control and β-Cell Function in Newly Diagnosed Type 2 Diabetes With Severe Hyperglycemia After Short-Term Intensive Insulin Therapy
Authors: Chen Harn-Shen , Wu Tzu-En , Jap Tjin-Shing , Hsiao Li-Chuan , Lee Shen-Hung , Lin Hong-Da 
Published: June 2008

OBJECTIVE—To evaluate whether treatment with insulin is advantageous compared with oral antidiabetes agents in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy.
RESEARCH DESIGN AND METHODS—Newly diagnosed type 2 diabetic patients with severe hyperglycemia were hospitalized and treated with intensive insulin injections for 10–14 days. The oral glucose tolerance test (OGTT) was performed after intensive insulin treatment. After discharge, the patients were randomized to receive either insulin injections or oral antidiabetes drugs (OADs) for further management. The OGTT was repeated 6 months later, and β-cell function and insulin sensitivity were evaluated again. These subjects were continually followed up for another 6 months to evaluate their long-term glycemic control.
RESULTS—At the 6th month of the study, the A1C level was significantly lower in the insulin group than in the OAD group (6.33 ± 0.70% vs. 7.50 ± 1.50%; P = 0.002). During the follow-up visit, the A1C level was still better in the insulin group (6.78 ± 1.21% vs. 7.84 ± 1.74%; P = 0.009). All parameters regarding β-cell function measured in the OGTT were improved significantly in both groups after 6 months of treatment. Compared with the OAD group, the homeostasis model assessment of β-cell function index, insulin area under the curve, and insulinogenic index were better in the insulin group.
CONCLUSIONS—A 6-month course of insulin therapy, compared with OAD treatment, could more effectively achieve adequate glycemic control and significant improvement of β-cell function in new-onset type 2 diabetic patients with severe hyperglycemia.
Coincidence of a Novel KCNJ11 Missense Variant R365H With a Paternally Inherited 6q24 Duplication in a Patient With Transient Neonatal Diabetes
Authors: Staník Juraj , Lethby Mark , Flanagan Sarah E. , Gašperíková Daniela , Milošovičová Beata , Lever Margaret , Bullman Hilary , Zubcevic Lejla , Hattersley Andrew T. , Ellard Sian , Ashcroft Frances M. , Klimeš Iwar 
Published: June 2008

OBJECTIVE—Neonatal diabetes is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent neonatal diabetes is mutations of the ATP-sensitive K+ channel subunits; in transient neonatal diabetes, chromosome 6q24 abnormalities are the most common cause.
RESEARCH DESIGN AND METHODS—We report a sporadic case of diabetes without ketoacidosis diagnosed on the fourth day of life.
RESULTS—Analysis of the KCNJ11 gene found a novel R365H mutation in the proband and her unaffected father. The functional analysis did not support pathogenicity of this variant. When the patient's diabetes remitted in the seventh month of life, the 6q24 region was analyzed and a paternally inherited duplication was identified.
CONCLUSIONS—Our case reports a coincidental novel KCNJ11 variant in a patient with transient neonatal diabetes due to a 6q24 duplication, illustrating the difficulty in testing neonates before the clinical course of neonatal diabetes is known.
Retrospective Assessment of Islet Cell Autoantibodies in Pancreas Organ Donors
Authors: Diamantopoulos Stavros , Allende Gloria , Ferreira Joseph M. , Ciancio Gaetano , Burke George W. , Pugliese Alberto 
Published: June 2008

OBJECTIVE—Of deceased pancreas donors, 3–4% may have autoantibodies (AAb) to pancreatic islet cell antigens; these autoantibodies are well-established markers of type 1 diabetes. We investigated whether donor AAb positivity could affect the outcome of pancreas transplantation.
RESEARCH DESIGN AND METHODS—We retrospectively tested AAb in 135 donors whose pancreata and kidneys were transplanted in type 1 diabetes patients. We measured AAb to glutamic acid decarboxylase (GAD-AAb), the tyrosine-phosphatase-like protein IA2 (IA2-AAb), and insulin (insulin-AAb). We then evaluated pancreas transplant outcome data.
RESULTS—Four of 135 (2.96%) donors were AAb positive: three donors had GAD-AAb, and one donor had insulin-AAb. Their respective recipients became insulin independent on follow-up. Three of the four recipients had normal, insulin-producing grafts 3–5.8 years after transplant. The recipient of the insulin-AAb–positive donor pancreas developed chronic rejection following discontinuation of immunosuppression 3.3 years after transplant.
CONCLUSIONS—Single AAb positivity did not affect the outcome of pancreas transplantation in our study.
Dietary Patterns and Risk of Incident Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Nettleton Jennifer A. , Steffen Lyn M. , Ni Hanyu , Liu Kiang , Jacobs David R. 
Published: June 2008

OBJECTIVE—We characterized dietary patterns and their relation to incident type 2 diabetes in 5,011 participants from the Multi-Ethnic Study of Atherosclerosis (MESA).
RESEARCH DESIGN AND METHODS—White, black, Hispanic, and Chinese adults, aged 45–84 years and free of cardiovascular disease and diabetes, completed food frequency questionnaires at baseline (2000–2002). Incident type 2 diabetes was defined at three follow-up exams (2002–2003, 2004–2005, and 2005–2007) as fasting glucose &gt;126 mg/dl, self-reported type 2 diabetes, or use of diabetes medication. Two types of dietary patterns were studied: four empirically derived (principal components analysis) and one author-defined (low-risk food pattern) as the weighted sum of whole grains, vegetables, nuts/seeds, low-fat dairy, coffee (positively weighted), red meat, processed meat, high-fat dairy, and soda (negatively weighted).
RESULTS—The empirically derived dietary pattern characterized by high intake of tomatoes, beans, refined grains, high-fat dairy, and red meat was associated with an 18% greater risk (hazard ratio per 1-score SD 1.18 [95% CI 1.06–1.32]; Ptrend = 0.004), whereas the empirically derived dietary pattern characterized by high intake of whole grains, fruit, nuts/seeds, green leafy vegetables, and low-fat dairy was associated with a 15% lower diabetes risk (0.85 [0.76–0.95]; Ptrend = 0.005). The low-risk food pattern was also inversely associated with diabetes risk (0.87 [0.81–0.99]; Ptrend = 0.04). Individual component food groups were not independently associated with diabetes risk. Associations were not modified by sex or race/ethnicity.
CONCLUSIONS—Multiple food groups collectively influence type 2 diabetes risk beyond that of the individual food groups themselves.
Legitimisation and Proximisation Values in the Discourse of Historic Change
Authors: Wieczorek Anna 
Published: June 2008

Legitimisation and Proximisation Values in the Discourse of Historic Change
This methodological-critical paper belongs to the field of pragmaticcognitive discourse analysis. It develops Cap's STA model of legitimisation (2005, 2006, 2008) and investigates various mechanisms legitimising the speaker's actions (or actions for which he bears responsibility) in political discourse of historic change. Proximisation as the salient feature of the model adds significantly to effectiveness of the speaker's continual attempt to convince the addressee of the rightness of political steps taken. It is a powerful and coercive tool "alerting the addressee [to] the proximity or imminence of phenomena which can be a ‘threat’ to the addressee" located in the deictic centre of a given event (Cap 2006:4) or a chain of events. The STA model accounts for the application of a three-dimensional pattern of the phenomenon in question, i.e. spatial, temporal, and axiological proximisation. However, the division does not exhaust the notion's potential, since properties of the dimensions mentioned enable us to classify them according to an extended taxonomic system in which they possess positive, negative, and neutral values (cf. Wieczorek 2008). Thus, the aim of this paper is to (a) analyse the interplay between a number of legitimisation strategies, (b) present the positive/negative/neutral classification of proximisation, and (c) comment on the nature of the interaction between and potency of the three dimensions and values. These can coexist within the body of one text, as well as within the body of one paragraph and their complementary character strengthens the overall goal of legitimisation providing various stimuli for the addressee to accept the speaker's stance, his decisions and actions, to comply with them, and to undertake actions intended by the speaker.
ThermoCalc-based numerical computations for temperature, fraction of solid phase and composition couplings in alloy solidification
Authors: Zhao Guangwei , Xu Daming , Fu Hengzhi 
Published: June 2008

Abstract
The directional solidification transport behaviors in blade-like castings of Al – Cu and Fe – C alloys were simulated based on a multilength-scale continuum model for solidification transport processes. The simulations were closely coupled with the commercial ThermoCalc package via its TQ-interface codes, for instantaneous determination of the related thermodynamic data at each calculation time step. Comparisons were made between the simulation results obtained by the ThermoCalc-coupled modeling and the model using the regression functions for the solidification thermodynamic data. The present numerical investigations confirm the feasibility of a close linkage of ThermoCalc software/Databases to the solidification simulations, but indicate an urgent need to cut down significantly the CPU-time spent for accessing the ThermoCalc/Databases for an efficient coupled computation.
Phase equilibria of the Al–Ni–Zn system at 340°C
Authors: Xu Honghui , Du Yong , Zhou Yichun , Zheng Xuejun , Xiong Wei , Liu Shuhong , Su Xuping , Yin Fucheng 
Published: June 2008

Abstract
The phase equilibria at 340°C of the Al – Ni – Zn system were investigated by combining the diffusion couple technique with the equilibrated alloys method. The samples were examined by means of optical microscopy, X-ray diffraction, scanning electron microscopy, and electron probe microanalysis. Two ternary compounds (1 and 2) were found to exist at 340°C. The solubilities of Zn in AlNi, Al3Ni2 and Al3Ni were determined to be about 20, 2 and 1 at.% Zn, respectively. The solubilities of Al in β1-NiZn and in were measured to be about 11.5 and 1 at.% Al, respectively. The solubilities of Zn in both AlNi3 and Al3Ni5 are below 1 at.% Zn.
Construction of the Al–Ni–Si phase diagram over the whole composition and temperature ranges: thermodynamic modeling supported by key experiments and first-principles calculations
Authors: Xiong Wei , Du Yong , Hu Rong-Xiang , Wang Jiong , Zhang Wei-Wei , Nash Philip , Lu Xiao-Gang 
Published: June 2008

Abstract
An extensive thermodynamic investigation of the Al – Ni – Si system is carried out via an integrated approach of calculation of phase diagrams, first-principles calculations, and key experiments. Eighteen decisive alloys are prepared in order to verify the existence of the previously reported ternary compounds and to provide new phase equilibrium data. Phase compositions, microstructure, and phase transition temperatures are determined using the combined techniques of X-ray diffraction, scanning electron microscopy, energy dispersion X-ray analysis, and differential thermal analysis. The order/disorder transition between disordered bcc_A2 and ordered bcc_B2 phases as well as that between disordered fcc_A1 and ordered L12 phase are described using a two-sublattice model. A self-consistent parameter set is finally obtained by considering the huge amount of experimental data including 13 vertical sections and 5 isothermal sections from both the literature and the present experiments. Almost all of the reliable phase diagram data can be well described by the present modeling. The reliability of the calculated thermodynamic properties for ternary phases is verified through enthalpy measurement employing drop calorimetry and first-principles calculations. The thermodynamic parameters obtained can also successfully predict most of the thermodynamic properties and describe the solidification path for the selected as-cast alloy Al6Ni55Si39.
Phase equilibria in the Y–Ti–Si system at 773 K
Authors: Zhan Yongzhong , Yu Zhengwen , Li Chunhui , Guo Qinghua , Hu Zhaohua , Zhuang Yinghong 
Published: June 2008

Abstract
Physico-chemical analysis techniques, including X-ray powder diffraction, scanning electron microscopy, optical microscopy and differential thermal analysis were employed in constructing the isothermal section of the Y – Ti – Si system at 773 K. The isothermal section consists of 12 single phase regions, 21 binary phase regions and 10 ternary phase regions. No ternary compound is found in the work. None of the phases in this system reveals a remarkable homogeneity range at 773 K.
Thermodynamic description of the Ce-Mg-Y and Mg-Nd-Y systems
Authors: Guo Cuiping , Du Zhenmin , Li Changrong 
Published: June 2008

Abstract
The thermodynamic modeling and optimization of the Ce-Mg, Ce-Y, Mg-Nd, Nd-Y, Ce-Mg-Y and Mg-Nd-Y systems have been carried out by means of the CALPHAD technique. The solution phases, liquid, body-centered cubic, face-centered cubic, hexagonal close-packed and double hexagonal close-packed, were described by the substitutional solution model. The isostructural MgCe, MgNd and MgY phases with B2 structure form continuous range of solid solutions in the Ce-Mg-Y and Mg-Nd-Y ternary systems. The order-disorder transition between the solutions with A2 structure and compounds with B2 structure in the systems has been taken into account and thermodynamically modeled. The other compounds Mg2Y, Mg24Y5, Mg3R, Mg41R5, Mg2R and Mg12Ce (R = Ce and Nd) in the Mg-R-Y system exhibit different solubilities of the third component. A set of self-consistent thermodynamic descriptions of the Ce-Mg-Y and Mg-Nd-Y systems was obtained.
First-principles calculations of the thermodynamic and elastic properties of the L12-based Al3RE (RE = Sc, Y, La–Lu)
Authors: Tao Xiaoma , Ouyang Yifang , Liu Huashan , Feng Yuanping , Du Yong , Jin Zhanpeng 
Published: June 2008

Abstract
First-principles calculations of the total energy and elastic properties of the L12-based Al3RE (RE = Sc, Y, Lanthanide) at T = 0 K are performed by using the projector augmented-wave method within the generalized gradient approximation. The lattice constants, formation enthalpies, elastic constants and bulk modulus of the L12-based Al3RE are obtained. Young's modulus, shear modulus and Poisson's ratios are also estimated in the present work. By using the Debye – Grüneisen model, the Debye temperatures, Grüneisen constants and the sound velocity are obtained for the L12-based Al3RE. All the calculated results are in good agreement with experimental values and other theoretical calculations available.
Thermodynamic description of multi-component multi-phase alloys and its application to the solidification process
Authors: Jie Wanqi , Zhang Ruijie , He Zhi 
Published: June 2008

Abstract
Metallic materials in engineering applications are mostly multi-component and multi-phase alloys. The solidification principles of these materials still lack quantitative description. In this work, the solute partition behavior and its influence on the solidification process of multi-component alloys are studied based on CALPHAD.
A complete thermodynamic model for the accurate calculation of the partition coefficients in solidification is described. The model is applied to Al – Si – Mg ternary alloys, and the predicted partition coefficients are compared with some former experimental data. Good agreement between the calculation results and the experimental data demonstrates the validity of the present model.
The variation of solute partition coefficients of both Si and Mg is studied in dendritic solidification of Al – Si – Mg alloys. It is found that the partition coefficient changes greatly during solidification. By coupling CALPHAD with a micro-scale solidification model, the predicted solidification path for different composition and cooling rates and the off-eutectic fraction of Al – Si – Mg alloys agrees well with the experimental results.
The conventional theory of constrained dendrite growth for binary alloys is extended to multi-component alloys based on the CALPHAD method with consideration of the solute interactions, through which the primary dendrite spacing is estimated.