bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Association Study of Type 2 Diabetes and Related Quantitative Traits With 222 Candidate Genes
Authors: Gaulton Kyle J. , Willer Cristen J. , Li Yun , Scott Laura J. , Conneely Karen N. , Jackson Anne U. , Duren William L. , Chines Peter S. , Narisu Narisu , Bonnycastle Lori L. , Luo Jingchun , Tong Maurine , Sprau Andrew G. , Pugh Elizabeth W. , Doheny Kimberly F. , Valle Timo T. , Abecasis Gonçalo R. , Tuomilehto Jaakko , Bergman Richard N. , Collins Francis S. , Boehnke Michael , Mohlke Karen L. 
Published: August 2008

OBJECTIVE—Type 2 diabetes is a common complex disorder with environmental and genetic components. We used a candidate gene–based approach to identify single nucleotide polymorphism (SNP) variants in 222 candidate genes that influence susceptibility to type 2 diabetes.
RESEARCH DESIGN AND METHODS—In a case-control study of 1,161 type 2 diabetic subjects and 1,174 control Finns who are normal glucose tolerant, we genotyped 3,531 tagSNPs and annotation-based SNPs and imputed an additional 7,498 SNPs, providing 99.9% coverage of common HapMap variants in the 222 candidate genes. Selected SNPs were genotyped in an additional 1,211 type 2 diabetic case subjects and 1,259 control subjects who are normal glucose tolerant, also from Finland.
RESULTS—Using SNP- and gene-based analysis methods, we replicated previously reported SNP-type 2 diabetes associations in PPARG, KCNJ11, and SLC2A2; identified significant SNPs in genes with previously reported associations (ENPP1 [rs2021966, P = 0.00026] and NRF1 [rs1882095, P = 0.00096]); and implicated novel genes, including RAPGEF1 (rs4740283, P = 0.00013) and TP53 (rs1042522, Arg72Pro, P = 0.00086), in type 2 diabetes susceptibility.
CONCLUSIONS—Our study provides an effective gene-based approach to association study design and analysis. One or more of the newly implicated genes may contribute to type 2 diabetes pathogenesis. Analysis of additional samples will be necessary to determine their effect on susceptibility.
Persistence of Pre-Diabetes in Overweight and Obese Hispanic Children
Authors: Goran Michael I. , Lane Christianne , Toledo-Corral Claudia , Weigensberg Marc J. 
Published: August 2008

OBJECTIVE—To examine changes in risk factors in overweight and obese Hispanic children at high risk of developing type 2 diabetes.
RESEARCH DESIGN AND METHODS—We recruited 128 overweight/obese Hispanic children with a family history of type 2 diabetes primarily from clinics in East Los Angeles. Children were evaluated annually for 4 years with an oral glucose tolerance test, applying American Diabetes Association criteria to define diabetes and pre-diabetes. Insulin sensitivity (Si), acute insulin response (AIR) to glucose, and β-cell function (BCF) were determined from frequently sampled intravenous glucose tolerance tests, and total body fat by dual-energy X-ray absorptiometry and intra-abdominal and subcutaneous abdominal adipose tissue (IAAT and SAAT) by magnetic resonance imaging were assessed in years 1, 2, and 4.
RESULTS—No subjects developed type 2 diabetes, 40% never had pre-diabetes, 47% had intermittent pre-diabetes with no clear pattern over time, and 13% had persistent pre-diabetes. At baseline, those with persistent pre-diabetes had lower BCF and higher IAAT. In repeated measures, Si deteriorated regardless of pre-diabetes, and there was a significant effect of pre-diabetes on AIR (42% lower in pre-diabetes; P = 0.01) and disposition index (34% lower in pre-diabetes; P = 0.021) and a significant interaction of pre-diabetes and time on IAAT (greater increase over time in those with pre-diabetes; P = 0.034).
CONCLUSIONS—In this group of Hispanic children at high risk of type 2 diabetes, 1) pre-diabetes is highly variable from year to year; 2) the prevalence of persistent pre-diabetes over 3 years is 13%; and 3) children with persistent pre-diabetes have lower BCF, due to a lower AIR, and increasing visceral fat over time.
Common Missense Variant in the Glucokinase Regulatory Protein Gene Is Associated With Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations
Authors: Orho-Melander Marju , Melander Olle , Guiducci Candace , Perez-Martinez Pablo , Corella Dolores , Roos Charlotta , Tewhey Ryan , Rieder Mark J. , Hall Jennifer , Abecasis Goncalo , Tai E. Shyong , Welch Cullan , Arnett Donna K. , Lyssenko Valeriya , Lindholm Eero , Saxena Richa , de Bakker Paul I.W. , Burtt Noel , Voight Benjamin F. , Hirschhorn Joel N. , Tucker Katherine L. , Hedner Thomas , Tuomi Tiinamaija , Isomaa Bo , Eriksson Karl-Fredrik , Taskinen Marja-Riitta , Wahlstrand Björn , Hughes Thomas E. , Parnell Laurence D. , Lai Chao-Qiang , Berglund Göran , Peltonen Leena , Vartiainen Erkki , Jousilahti Pekka , Havulinna Aki S. , Salomaa Veikko , Nilsson Peter , Groop Leif , Altshuler David , Ordovas Jose M. , Kathiresan Sekar 
Published: August 2008

OBJECTIVE—Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry and to fine- map across the associated genomic interval.
RESEARCH DESIGN AND METHODS—We performed association studies in 12 independent cohorts comprising &gt;45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the U.S., African Americans from the U.S., Hispanics of Caribbean origin, and Chinese, Malays, and Asian Indians from Singapore). We conducted genetic fine-mapping across the ∼417-kb region of linkage disequilibrium spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap single nucleotide polymorphisms (SNPs) and genotyping 104 SNPs across the associated genomic interval.
RESULTS—We provide comprehensive evidence that GCKR rs780094 is associated with opposite effects on fasting plasma triglyceride (Pmeta = 3 × 10−56) and glucose (Pmeta = 1 × 10−13) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reactive protein (CRP) level (P = 5 × 10−5). Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r2 = 0.93 with rs780094) as the strongest association signal in the region.
CONCLUSIONS—These findings point to a molecular mechanism in humans by which higher triglycerides and CRP can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism.
Lack of FFAR1/GPR40 Does Not Protect Mice From High-Fat Diet–Induced Metabolic Disease
Authors: Lan Hong , Hoos Lizbeth M. , Liu Li , Tetzloff Glen , Hu Weiwen , Abbondanzo Susan J. , Vassileva Galya , Gustafson Eric L. , Hedrick Joseph A. , Davis Harry R. 
Published: August 2008

OBJECTIVE—FFAR1/GPR40 is a G-protein–coupled receptor expressed predominantly in pancreatic islets mediating free fatty acid–induced insulin secretion. However, the physiological role of FFAR1 remains controversial. It was previously reported that FFAR1 knockout (Ffar1−/−) mice were resistant to high-fat diet–induced hyperinuslinemia, hyperglycemia, hypertriglyceridemia, and hepatic steatosis. A more recent report suggested that although FFAR1 was necessary for fatty acid–induced insulin secretion in vivo, deletion of FFAR1 did not protect pancreatic islets against fatty acid–induced islet dysfunction. This study is designed to investigate FFAR1 function in vivo using a third line of independently generated Ffar1−/− mice in the C57BL/6 background.
RESEARCH DESIGN AND METHODS—We used CL-316,243, a β3 adrenergic receptor agonist, to acutely elevate blood free fatty acids and to study its effect on insulin secretion in vivo. Ffar1+/+ (wild-type) and Ffar1−/− (knockout) mice were placed on two distinct high-fat diets to study their response to diet-induced obesity.
RESULTS—Insulin secretion was reduced by ∼50% in Ffar1−/− mice, confirming that FFAR1 contributes significantly to fatty acid stimulation of insulin secretion in vivo. However, Ffar1+/+ and Ffar1−/− mice had similar weight, adiposity, and hyperinsulinemia on high-fat diets, and Ffar1−/− mice showed no improvement in glucose or insulin tolerance tests. In addition, high-fat diet induced comparable levels of lipid accumulation in livers of Ffar1+/+ and Ffar1−/− mice.
CONCLUSIONS—FFAR1 is required for normal insulin secretion in response to fatty acids; however, Ffar1−/− mice are not protected from high-fat diet–induced insulin resistance or hepatic steatosis.
Significantly Enhanced Photoluminescence of Doped Polymer‐Metal Hybrid Nanotubes
Authors: Park Dong Hyuk , Kim Hyun Seung , Jeong Mi‐Yun , Lee Yong Baek , Kim Hyun‐Jun , Kim Dae‐Chul , Kim Jeongyong , Joo Jinsoo 
Published: August 2008

AbstractWe report on the significantly enhanced photoluminescence (PL) of hybrid double‐layered nanotubes (HDLNTs) consisting of poly(3‐methylthiophene) (P3MT) nanotubes with various doping levels enveloped by an inorganic, nickel (Ni) metal nanotube. From laser confocal microscopy PL experiments on a single strand of the doped‐P3MT nanotubes and of their HDLNTs, the PL peak intensity of the HDLNT systems increased remarkably up to ∼350 times as the doping level of the P3MT nanotubes of the HDLNTs increased, which was confirmed by measurements of the quantum yield. In a comparison of the normalized ultraviolet and visible absorption spectra of the doped‐P3MT nanotubes and their HDLNTs, new absorption peaks corresponding to surface‐plasmon (SP) energy were created at 563 and 615 nm after the nanoscale Ni metal coating onto the P3MT nanotubes, and their intensity increased on increasing the doping level of the P3MT nanotube. The doping‐induced bipolaron peaks of the HDLNTs of doped‐P3MT/Ni were relatively reduced, compared with those of the doped‐P3MT nanotubes before the Ni coating, due to the charge‐transfer effect in the SP‐resonance (SPR) coupling. Both energy‐transfer and charge‐transfer effects due to SP resonance contributed to the very‐large enhancement of the PL efficiency of the doped‐P3MT‐based HDLNTs.
The Influence of UV Irradiation on Ketonic Defect Emission in Fluorene‐Based Copolymers
Authors: Scheiber Horst , Graf Michael , Plank Harald , Zojer Egbert , Slugovc Christian , Kappaun Stefan , Galbrecht Frank , Scherf Ullrich , List Emil J. W. 
Published: August 2008

AbstractThe influence of UV irradiation in inert atmosphere on the emission spectrum of fluorenone containing poly[9,9‐bis(2‐ethyl)hexylfluorene] (PF2/6) has been investigated by means of optical absorption, photoluminescence (PL) and Fourier transform infrared (FTIR) spectroscopy. It is shown that a substantial reduction of green emission arising from ketonic defect sites can be achieved by irradiation of thin films with UV light. This is found to be accompanied by partial cross‐linking of the films. FTIR measurements show no reduction of the C=O stretching mode upon irradiation, and, moreover, the degree of cross‐linking does not scale with the relative fluorenone content (0.1, 0.5, and 5%). Therefore, the reduced emission intensity in the green spectral region is rather associated with the occurrence of interruptions in the polymer backbone, which reduce the effective conjugation length and subsequently inhibit the energy transfer onto the ketonic defect sites. The found results enabled us to build organic light emitting devices (OLEDs) that can be structured by selective illumination of the emitting layer with an intense UV light source. This method allows for the fabrication of rather efficient (2000 cd m−2 at 7 V) two‐color OLEDs.
Arsenic and iron removal from water using constructed soil filter—a novel approach
Authors: Nemade Pravin , Kadam Avinash M. , Shankar Hariharan S. 
Published: August 2008

AbstractArsenic poisoning is a global problem. It is known that groundwater in Bangladesh and West Bengal predominantly contains As(III) and concentrations of Fe(II) which are often too low for removal of arsenic in optimum quantities. To eliminate arsenic from drinking water, several basic methods such as coagulation, adsorption, ion exchange, filtration, membrane processes, are reported. To deal with this issue on a small to large scale, we present a novel approach to remove arsenic and iron from water by constructed soil filter (CSF).In CSF, As (III) is oxidized to As(V) by media via natural oxidation and subsequently, arsenic is co‐precipitated with iron. Here water containing arsenic, iron, and phosphate is passed through the CSF media at the rate of 100 ml/min. Results show a mean residence time of 8.6 min and a holdup of 1.85 l. Results of six runs show that with initial As(III) of 300 µg/l and iron concentration of 5–10 mg/l, residual arsenic levels below 10 ppb and residual iron < 0.30 mg/l in water can be achieved.In CSF, no chemicals are needed for the oxidation of As(III) to As(V). The oxidation takes place due to the presence of various oxides such as iron, manganese, aluminum, and the microbial diversity in the media of soil bioreactor. Such a novel technology is also applied for purification of water and wastewater. Copyright © 2008 Curtin University of Technology and John Wiley & Sons, Ltd.
The behavior of dithiocarbimate derivative as safety accelerator of natural rubber compounds
Authors: Mariano Roberta M. , da Costa Helson M. , Oliveira Marcelo R. L. , Rubinger Mayura M. M. , Visconte Leila L. Y. 
Published: August 2008

AbstractA conventional vulcanization system containing tetrabutylammonium bis(4‐methylphenyldithiocarbimato)zincate(II) (ZNIBU) was used for curing of natural rubber (NR) compounds. Rheometric (ts1, t90, and CRI) and mechanical properties, such as tensile and tear strengths and modulus at 300%, were measured to evaluate the acceleration potential of ZNIBU. Commercial accelerators (TMTD, MBTS, and CBS) and a binary system CBS/ZNIBU were also tested for comparison purposes. It was observed that ZNIBU alone does not give either safe scorch time or cure rates appropriate for industrial applications. Nevertheless, mechanical properties are comparable to those given by the other accelerators used. As for the binary system, positive synergistic effects can be found in tear strength and modulus of NR vulcanizates. Besides, ZNIBU does not contribute for the formation of nitrosamines in the vulcanization process. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Glycan Arrays on Aluminum‐Coated Glass Slides
Authors: Tseng Susan Y. , Wang Cheng‐Chi , Lin Chin‐Wei , Chen Cheng‐Lung , Yu Wen‐Yueh , Chen Chung‐Hsuan , Wu Chung‐Yi , Wong Chi‐Huey 
Published: August 2008

AbstractWe have developed a novel method of immobilizing glycans onto aluminum‐coated glass (ACG) slides for potential use in disease diagnosis and drug discovery. The quality of these sugar chips can be assessed by mass spectrometry and fluorescence measurements with high sensitivity. The unique properties of ACG slides include: 1) the metal oxide layer on the surface can be activated for grafting organic compounds such as modified oligosaccharides; 2) the surface remains electrically conductive, and the grafted oligosaccharides can be simultaneously characterized by mass spectrometry and carbohydrate‐binding assay; and 3) the slides are more sensitive than transparent glass slides in binding analysis. To demonstrate this, we synthesized a model compound of mannose with a built‐in photocleavable linker bound to the ACG slide surface. The molecular weight of the grafted mannose was identified by mass spectrometry, and the slide was subjected to biotinylated ConA binding followed by Cy3‐tagged streptavidin detection. This method was further extended to the preparation of glycan arrays containing lactose and the cancer antigen Globo H.
Tandem Hydroformylation–Hydrogenation of 1‐Decene Catalyzed by Rh‐Bidentate Bis(trialkylphosphine)s
Authors: Ichihara Takeo , Nakano Koji , Katayama Masaya , Nozaki Kyoko 
Published: August 2008

AbstractA series of 2,2′‐bis[(dialkylphosphino)methyl]biphenyls (alkyl‐BISBIs) were synthesized and applied to the tandem hydroformylation–hydrogenation of 1‐decene. The alkyl‐BISBI ligands with “small” primary alkyl groups such as methyl or n‐hexyl groups on the phosphorus atoms provided 1‐alkanols selectively, whereas those with larger alkyl groups such as isopropyl or neopentyl groups showed much lower conversion from alkanals to alkanols. Observation of rhodium complexes of the BISBI‐type ligands under H2/CO atmosphere revealed that the presence of a stable [RhH(CO)2(ligand)] species seems to be less favorable for the second step, the hydrogenation of aldehydes.
Switch‐Peptides: Design and Characterization of Controllable Super‐Amyloid‐Forming Host–Guest Peptides as Tools for Identifying Anti‐Amyloid Agents
Authors: Camus Marie‐Stéphanie , Dos Santos Sonia , Chandravarkar Arunan , Mandal Bhubaneswar , Schmid Adrian W. , Tuchscherer Gabriele , Mutter Manfred , Lashuel Hilal A. 
Published: August 2008

AbstractSeveral amyloid‐forming proteins are characterized by the presence of hydrophobic and highly amyloidogenic core sequences that play critical roles in the initiation and progression of amyloid fibril formation. Therefore targeting these sequences represents a viable strategy for identifying candidate molecules that could interfere with amyloid formation and toxicity of the parent proteins. However, the highly amyloidogenic and insoluble nature of these sequences has hampered efforts to develop high‐throughput fibrillization assays. Here we describe the design and characterization of host–guest switch peptides that can be used for in vitro mechanistic and screening studies that are aimed at discovering aggregation inhibitors that target highly amyloidogenic sequences. These model systems are based on a host–guest system where the amyloidogenic sequence (guest peptide) is flanked by two β‐sheet‐promoting (Leu‐Ser)n oligomers as host sequences. Two host–guest peptides were prepared by using the hydrophobic core of Aβ comprising residues 14–24 (HQKLVFFAEDV) as the guest peptide with switch elements inserted within (peptide 1) or at the N and C termini of the guest peptide (peptide 2). Both model peptides can be triggered to undergo rapid self‐assembly and amyloid formation in a highly controllable manner and their fibrillization kinetics is tuneable by manipulating solution conditions (for example, peptide concentration and pH). The fibrillization of both peptides reproduces many features of the full‐length Aβ peptides and can be inhibited by known inhibitors of Aβ fibril formation. Our results suggest that this approach can be extended to other amyloid proteins and should facilitate the discovery of small‐molecule aggregation inhibitors and the development of more efficacious anti‐amyloid agents to treat and/or reverse the pathogenesis of neurodegenerative and systemic amyloid diseases.
Phosphoric Acid Catalyzed Enantioselective Transfer Hydrogenation of Imines: A Density Functional Theory Study of Reaction Mechanism and the Origins of Enantioselectivity
Authors: Marcelli Tommaso , Hammar Peter , Himo Fahmi 
Published: August 2008

AbstractThe phosphoric acid catalyzed reaction of 1,4‐dihydropyridines with N‐arylimines has been investigated by using density functional theory. We first considered the reaction of acetophenone PMP‐imine (PMP=p‐methoxyphenyl) with the dimethyl Hantzsch ester catalyzed by diphenyl phosphate. Our study showed that, in agreement with what has previously been postulated for other reactions, diphenyl phosphate acts as a Lewis base/Brønsted acid bifunctional catalyst in this transformation, simultaneously activating both reaction partners. The calculations also showed that the hydride transfer transition states for the E and Z isomers of the iminium ion have comparable energies. This observation turned out to be crucial to the understanding of the enantioselectivity of the process. Our results indicate that when using a chiral 3,3′‐disubstituted biaryl phosphoric acid, hydride transfer to the Re face of the (Z)‐iminium is energetically more favorable and is responsible for the enantioselectivity, whereas the corresponding transition states for nucleophilic attack on the two faces of the (E)‐iminium are virtually degenerate. Moreover, model calculations predict the reversal in enantioselectivity observed in the hydrogenation of 2‐arylquinolines, which during the catalytic cycle are converted into (E)‐iminium ions that lack the flexibility of those derived from acyclic N‐arylimines. In this respect, the conformational rigidity of the dihydroquinolinium cation imposes an unfavorable binding geometry on the transition state for hydride transfer on the Re face and is therefore responsible for the high enantioselectivity.
A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma
Authors: Musto Pellegrino , Petrucci Maria Teresa , Bringhen Sara , Guglielmelli Tommasina , Caravita Tommaso , Bongarzoni Velia , Andriani Alessandro , D'Arena Giovanni , Balleari Enrico , Pietrantuono Giuseppe , Boccadoro Mario , Palumbo Antonio 
Published: August 2008

AbstractBACKGROUND.Bisphosphonates (BPs) are effective in the prevention and treatment of skeletal‐related events (SREs) in patients with symptomatic myeloma who are receiving chemotherapy. Recent data also suggest a possible antineoplastic activity of BPs. Few studies published to date have explored the role of BPs in patients with untreated, asymptomatic myeloma (AM). No data are available on the efficacy of zoledronic acid in these patients.METHODS.The authors conducted a prospective, multicenter, open‐label, phase 3, randomized trial comparing the administration of zoledronic acid versus simple observation in patients with AM. One‐hundred sixty‐three patients were enrolled and randomized (1:1) to receive zoledronic acid (n = 81 patients) or not to receive zoledronic acid (n = 82 patients) for 1 year at a dose of 4 mg monthly as a single, 15‐minute, intravenous infusion.RESULTS.After a median follow‐up of 64.7 person‐months, 44.4% of patients in the zoledronic acid group and 45.1% of the control group progressed to ‘symptomatic’ myeloma requiring chemotherapy (P = .9307). The median time to progression was 67 months and 59 months for the treatment and control groups, respectively (P = .8312). At progression, SREs were significantly lower in the zoledronic acid‐treated group (55.5%) than in the control group (78.3%; P = .041), whereas anemia, renal failure, and extramedullary disease were not statistically different. More frequent adverse events observed in the zoledronic acid‐treated group were asymptomatic hypocalcemia and fever. One patient developed reversible osteonecrosis of the jaw. No renal failure caused by zoledronic acid was reported.CONCLUSIONS.The monthly use of zoledronic acid for 1 year in patients with AM reduced the development of SREs at progression but did not influence the natural history of the disease. Cancer 2008. © 2008 American Cancer Society.