bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome‐Wide Family‐Based Linkage Analysis of Exome Chip Variants and Cardiometabolic Risk
Authors: Hellwege Jacklyn N. , Palmer Nicholette D. , Raffield Laura M. , Ng Maggie C.Y. , Hawkins Gregory A. , Long Jirong , Lorenzo Carlos , Norris Jill M. , Ida Chen Y.‐D. , Speliotes Elizabeth K. , Rotter Jerome I. , Langefeld Carl D. , Wagenknecht Lynne E. , Bowden Donald W. 
Published: April 2014

ABSTRACTLinkage analysis of complex traits has had limited success in identifying trait‐influencing loci. Recently, coding variants have been implicated as the basis for some biomedical associations. We tested whether coding variants are the basis for linkage peaks of complex traits in 42 African‐American (n = 596) and 90 Hispanic (n = 1,414) families in the Insulin Resistance Atherosclerosis Family Study (IRASFS) using Illumina HumanExome Beadchips. A total of 92,157 variants in African Americans (34%) and 81,559 (31%) in Hispanics were polymorphic and tested using two‐point linkage and association analyses with 37 cardiometabolic phenotypes. In African Americans 77 LOD scores greater than 3 were observed. The highest LOD score was 4.91 with the APOE SNP rs7412 (MAF = 0.13) with plasma apolipoprotein B (ApoB). This SNP was associated with ApoB (P‐value = 4 × 10−19) and accounted for 16.2% of the variance in African Americans. In Hispanic families, 104 LOD scores were greater than 3. The strongest evidence of linkage (LOD = 4.29) was with rs5882 (MAF = 0.46) in CETP with HDL. CETP variants were strongly associated with HDL (0.00049 < P‐value <4.6 × 10−12), accounting for up to 4.5% of the variance. These loci have previously been shown to have effects on the biomedical traits evaluated here. Thus, evidence of strong linkage in this genome wide survey of primarily coding variants was uncommon. Loci with strong evidence of linkage was characterized by large contributions to the variance, and, in these cases, are common variants. Less compelling evidence of linkage and association was observed with additional loci that may require larger family sets to confirm.
Bayesian Latent Variable Collapsing Model for Detecting Rare Variant Interaction Effect in Twin Study
Authors: He Liang , Sillanpää Mikko J. , Ripatti Samuli , Pitkäniemi Janne 
Published: April 2014

ABSTRACTBy analyzing more next‐generation sequencing data, researchers have affirmed that rare genetic variants are widespread among populations and likely play an important role in complex phenotypes. Recently, a handful of statistical models have been developed to analyze rare variant (RV) association in different study designs. However, due to the scarce occurrence of minor alleles in data, appropriate statistical methods for detecting RV interaction effects are still difficult to develop. We propose a hierarchical Bayesian latent variable collapsing method (BLVCM), which circumvents the obstacles by parameterizing the signals of RVs with latent variables in a Bayesian framework and is parameterized for twin data. The BLVCM can tackle nonassociated variants, allow both protective and deleterious effects, capture SNP‐SNP synergistic effect, provide estimates for the gene level and individual SNP contributions, and can be applied to both independent and various twin designs. We assessed the statistical properties of the BLVCM using simulated data, and found that it achieved better performance in terms of power for interaction effect detection compared to the Granvil and the SKAT. As proof of practical application, the BLVCM was then applied to a twin study analysis of more than 20,000 gene regions to identify significant RVs associated with low‐density lipoprotein cholesterol level. The results show that some of the findings are consistent with previous studies, and we identified some novel gene regions with significant SNP–SNP synergistic effects.
Changing hydrologic connectivity due to permafrost thaw in the lower Liard River valley, NWT, Canada
Authors: Connon Ryan F. , Quinton William L. , Craig James R. , Hayashi Masaki 
Published: April 2014

AbstractFlows from river basins in northwestern Canada have been rising in the last two decades as a result of climate warming. In the wetland‐dominated basins that characterise the southern margin of permafrost, permafrost thaw and disappearance, and resulting land‐cover change, is occurring at an unprecedented rate. The impact of this thaw on runoff generation in headwater basins is poorly understood. Permafrost thaw has the potential to fundamentally alter the cycling and storage of moisture inputs in this region by altering the type and relative proportions of the major land‐cover types, such as peat plateaus, channel fens and flat bogs. This paper examines streamflow changes in the four Water Survey of Canada gauged river basins (152–2050 km2) in the lower Liard River valley, Northwest Territories, Canada, a region where permafrost thaw has produced widespread loss of forest and concomitant expansion of permafrost‐free wetlands. Annual runoff in the lower Liard Valley increased by between 112 and 160 mm over the period of 1996–2012. The Mann‐Kendall non‐parametric statistical test and the Kendall‐Theil robust line were used to ascertain changes in streamflow. Historical aerial photographs from 1977 and high‐resolution satellite imagery (WorldView 2) from 2010 were used to measure the rate and pattern of permafrost thaw in a representative 6 km2 area of Scotty Creek. Permafrost thaw‐induced land‐cover change is both increasing the adjacency between runoff producing and transmitting land cover types and transforming certain land covers that store water into ones that produce runoff. This land‐cover change was found to be the single most important factor (37–61 mm) contributing to the observed increase in river discharge. Other contributing factors include increases in plateau runoff contributing areas (20–32 mm), increases in annual effective precipitation depth (18–30 mm), contribution of water from the melt of ice within permafrost (9 mm) and increases in baseflow (0.9–6.8 mm). Although runoff has significantly (p < 0.05) increased in all four basins, the largest increases are in basins with a relatively high cover of flat bogs. Copyright © 2014 John Wiley & Sons, Ltd.
Novel biomimetic tripolymer scaffolds consisting of chitosan, collagen type 1, and hyaluronic acid for bone marrow‐derived human mesenchymal stem cells‐based bone tissue engineering
Authors: Mathews Smitha , Bhonde Ramesh , Gupta Pawan Kumar , Totey Satish 
Published: April 2014

AbstractHuman bone marrow‐derived mesenchymal stem cells (hMSCs) are an ideal osteogenic cell source for bone tissue engineering (BTE). A scaffold, in the context of BTE, is the extracellular matrix (ECM) that provides the unique microenvironment and play significant role in regulating cell behavior, differentiation, and development in an in vitro culture system. In this study, we have developed novel biomimetic tripolymer scaffolds for BTE using an ECM protein, collagen type 1; an ECM glycosaminoglycan, hyaluronic acid; and a natural osteoconductive polymer, chitosan. The scaffolds were characterized by scanning electron microscopy (SEM) and swelling ratio. The scaffolds were seeded with hMSCs and tested for cytocompatibility and osteogenic potential. The scaffolds supported cell adhesion, enhanced cell proliferation, promoted cell migration, showed good cell viability, and osteogenic potential. The cells were able to migrate out from the scaffolds in favorable conditions. SEM, alkaline phosphatase assay, and immunofluorescent staining confirmed the differentiation of hMSCs to osteogenic lineage in the scaffolds. In conclusion, we have successfully developed biomimetic scaffolds that supported the proliferation and differentiation of hMSCs. These scaffolds hold great promise as a cell‐delivery vehicle for regenerative therapies and as a support system for enhancing bone regeneration. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1825–1834, 2014.
Fluorescent in situ hybridization of synaptic proteins imaged with super‐resolution STED microscopy
Authors: Zhang William I. , Röhse Heiko , Rizzoli Silvio O. , Opazo Felipe 
Published: April 2014

ABSTRACTSuper‐resolution fluorescence microscopy is still a developing field. One of the limitations has been that standard labeling assays, which had been developed for conventional imaging, must be adjusted and optimized for each super‐resolution method. These methods are more sensitive to noise, and require more intense labeling than conventional microscopy, which is not always trivial to achieve. Here, we describe the use of stimulation‐emission depletion (STED) microscopy to locate messenger RNAs (mRNAs) in single neurons with high spatial precision. We address several technical difficulties we encountered in using fluorescent in situ hybridization (FISH) for STED imaging. We optimized the experimental protocol to detect mRNAs and proteins simultaneously, by performing FISH and immunostaining on the same samples. We tested our imaging approach in primary hippocampal neurons, studying the mRNAs of three important presynaptic proteins (synaptobrevin, synaptotagmin, and synaptophysin). Our approach allowed us to relate changes in mRNA levels and localization to neuronal physiology, under different activity regimes and also during neuronal development. We conclude that FISH can be performed efficiently using super‐resolution techniques. This should contribute significantly to the clarification of the molecular mechanisms that govern mRNA distribution and dynamics within cells. Microsc. Res. Tech. 77:517–527, 2014. © 2014 Wiley Periodicals, Inc.
Practical methods for improving homogeneity in 3 tesla breast imaging
Authors: Winkler Simone A. , Rutt Brian K. 
Published: April 2014

PurposeTo improve image contrast and
field homogeneity in 3 Tesla (T) breast MR.Materials and MethodsTwo practical
shimming methods for 3T breast MR are presented; low‐cost passive shimming using local pads of high dielectric permittivity (εr from 0 to 100), and two‐channel radiofrequency (RF) shimming (adjusting Q‐I amplitude ratios and phase differences of 0 to −4 dB and 90 to 45 degrees), as well as a combination of both methods. The technique has been studied both in simulation using a numerical body model with added mammary tissue and in vivo in six subjects.ResultsLarge improvements are observed with both methods, leading to a decrease in left–right
asymmetry ratio of 1.24 to 1.00 (simulation) and from 1.26 to 1.01 (in vivo). RF safety was not adversely affected.ConclusionBoth RF shimming and dielectric shimming were shown to improve inhomogeneity in the
field in 3T breast MR. J. Magn. Reson. Imaging 2015;41:992–999. © 2014 Wiley Periodicals, Inc.
Measurement of tumor blood flow in head and neck squamous cell carcinoma by pseudo‐continuous arterial spin labeling: Comparison with dynamic contrast‐enhanced MRI
Authors: Fujima Noriyuki , Kudo Kohsuke , Tsukahara Akiko , Yoshida Daisuke , Sakashita Tomohiro , Homma Akihiro , Tha Khin Khin , Shirato Hiroki 
Published: April 2014

PurposeTo investigate the feasibility of tumor blood flow (TBF) measurement in head and neck squamous cell carcinoma (HNSCC) using pseudo‐continuous arterial spin labeling (pCASL) in a comparison with dynamic contrast‐enhanced (DCE) perfusion.Materials and MethodsWe prospectively scanned 18 patients with HNSCC using 3T magnetic resonance imaging (MRI) with both pCASL and DCE perfusion. Quantitative TBF value in the whole‐tumor region of interest (ROI), and regional TBF in the ROIs of the central and peripheral areas in the tumor were respectively measured. Relative TBF value in the whole‐tumor ROI was also calculated. We determined the correlation and agreement between each measured TBF by pCASL and DCE perfusion using Pearson's correlation coefficients, intraclass correlation coefficients (ICC), and Bland–Altman analysis.ResultsIn the whole‐tumor ROIs, significant correlation was observed between the absolute TBF values (r = 0.72, P < 0.01), with an ICC of 0.72; moreover, higher correlation was observed in the relative TBF (r = 0.79). The correlation was higher in the peripheral ROI (r = 0.70) than the central ROI (r = 0.65), with an ICC of 0.62 and 0.54, respectively. Bland–Altman plots revealed the underestimation of TBF by pCASL in central ROIs.ConclusionTBF measurement by pCASL was feasible in patients with HNSCC. J. Magn. Reson. Imaging 2015;41:983–991. © 2014 Wiley Periodicals, Inc.
Minimization of carryover for high‐throughput liquid chromatography with tandem mass spectrometry analysis of 14 mycotoxins in corn grits
Authors: Tamura Masayoshi , Matsumoto Keiko , Watanabe Jun , Iida Junko , Nagatomi Yasushi , Mochizuki Naoki 
Published: April 2014

A method for the simultaneous analysis of 14 mycotoxins with the minimization of carryover was developed. Our verification experiments suggested that the carryover occurred due to the chelation of fumonisins with the metal. To wash the fumonisins from the metal, the inner surface of the injection needle was rinsed with 10 mM trisodium citrate and 1% formic acid in water/methanol/acetonitrile/isopropanol after each injection, and the analysis was performed on a metal‐free Mastro C18 column. This approach remarkably minimized the carryover of fumonisins. Fourteen mycotoxins in samples were extracted with 2% acetic acid in water/acetonitrile and a quick, easy, cheap, effective, rugged, and safe extraction kit, purified on a MultiSep 229 Ochra, and then quantified by liquid chromatography with tandem mass spectrometry. Determinations performed using this method produced a linearity greater than 0.99 and recoveries ranging from 72.6 to 117.4%, with good intraday precision from 4.0 to 12.4%, and interday precision from 6.5 to 17.0%. The limits of detection ranged from 0.01 to 0.71 μg/kg, demonstrating that a highly sensitive method for the simultaneous analysis of mycotoxins over a wide range of concentrations was achieved with minimal carryover. When 12 samples of commercially available corn grits were analyzed with this method, deoxynivalenol, fumonisin B1, fumonisin B2, fumonisin B3, and zearalenone were present most frequently.
Determination of Sudan dyes in chili pepper powder by online solid‐phase extraction with a butyl methacrylate monolithic column coupled to liquid chromatography with tandem mass spectrometry
Authors: Liu Yao , Wang Man‐Man , Ai Lian‐Feng , Zhang Chang‐Kun , Li Xin , Wang Xue‐Sheng 
Published: April 2014

A poly(butyl methacrylate‐co‐ethylene dimethacrylate) monolithic column was fabricated and used as a novel sorbent for online solid‐phase extraction coupled to liquid chromatography with tandem mass spectrometry for the simultaneous determination of Sudan I–IV in chili pepper powder. The prepared columns were characterized by scanning electron microscopy, nitrogen adsorption‐desorption, and pressure drop measurements. Online solid‐phase extraction was performed on the synthesized monolithic column using 10 mM ammonium acetate solution as the loading solution with the aid of an online cleanup chromatography system. The desorption of Sudan I–IV was achieved with acetonitrile as the eluting solution at the flow rate of 0.5 mL/min. The extracted analytes were subsequently eluted into a C18 analytical column for chromatographic separation using a mixture of 10% acetonitrile/90% formic acid (0.5%) solution as the mobile phase. Under the optimized conditions, the developed method had linear range of 1.0–50 μg/kg, a detection limit of 0.3 μg/kg, and a quantification limit of 1.0 μg/kg for each analyte. The intraday and interday recoveries of Sudan I–IV in chili pepper powder samples ranged from 94.8 to 100.9% and 94.9 to 99.4%, respectively. The intraday and interday precision were between 3.37–7.01% and 5.01–7.68%, respectively.
COL6A3 expression in adipocytes associates with insulin resistance and depends on PPARγ and adipocyte size
Authors: Dankel Simon N. , Svärd Jessica , Matthä Simone , Claussnitzer Melina , Klöting Nora , Glunk Viktoria , Fandalyuk Zinayida , Grytten Elise , Solsvik Margit H. , Nielsen Hans‐Jørgen , Busch Christian , Hauner Hans , Blüher Matthias , Skurk Thomas , Sagen Jørn V. , Mellgren Gunnar 
Published: April 2014

ObjectiveCOL6A3 may modulate adipose tissue function in obesity and insulin resistance. A role for human adipocytes linking COL6A3 with insulin resistance warrants exploration.MethodsCOL6A3 mRNA in abdominal subcutaneous adipose samples was compared between (1) BMI‐matched obese subjects resistant or sensitive to insulin (surgical whole tissue biopsies, n = 30/group), (2) lean/overweight and obese subjects (isolated adipocytes from collagenase‐treated surgical biopsies, n = 11/group), (3) developing primary human adipocytes with/without knockdown of the insulin‐sensitizing adipogenic gene PPARG (collagenase‐treated lipoaspirate, n = 5), and (4) small and large adipocytes from lean/overweight subjects (collagenase‐treated surgical biopsies or lipoaspirate, n = 10). Insulin resistance and sensitivity were assessed by euglycemic‐hyperinsulinemic clamp (glucose infusion rate <60 and >70 μmol kg−1 min−1, respectively) (1), or by HOMA‐IR and TG/HDL ratio (2).ResultsWhole tissue COL6A3 mRNA was 2.6‐fold higher in insulin resistant compared to sensitive subjects (P < 0.001). In isolated adipocytes, COL6A3 mRNA correlated positively with BMI (P = 0.007), HOMA‐IR (P = 0.039), and TG/HDL (P = 0.004). PPARG knockdown in developing adipocytes increased COL6A3 mRNA 1.5‐fold (P = 0.043). The inverse relationship with adipocyte development was further supported by 2.8‐fold higher COL6A3 mRNA in small compared to large adipocytes (P = 0.004).ConclusionIncreased adipocyte COL6A3 expression associates with insulin resistance in humans, which may involve impaired PPARγ‐mediated adipocyte development.
Quantification of peptides from immunoglobulin constant and variable regions by LC‐MRM MS for assessment of multiple myeloma patients
Authors: Remily‐Wood Elizabeth R. , Benson Kaaron , Baz Rachid C. , Chen Y. Ann , Hussein Mohamad , Hartley‐Brown Monique A. , Sprung Robert W. , Perez Brianna , Liu Richard Z. , Yoder Sean J. , Teer Jamie K. , Eschrich Steven A. , Koomen John M. 
Published: April 2014

PurposeQuantitative MS assays for Igs are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, for example, multiple myeloma (MM).Experimental designUsing LC‐MS/MS data, Ig constant region peptides, and transitions were selected for LC‐MRM MS. Quantitative assays were used to assess Igs in serum from 83 patients. RNA sequencing and peptide‐based LC‐MRM are used to define peptides for quantification of the disease‐specific Ig.ResultsLC‐MRM assays quantify serum levels of Igs and their isoforms (IgG1–4, IgA1–2, IgM, IgD, and IgE, as well as kappa (κ) and lambda (λ) light chains). LC‐MRM quantification has been applied to single samples from a patient cohort and a longitudinal study of an IgE patient undergoing treatment, to enable comparison with existing clinical methods. Proof‐of‐concept data for defining and monitoring variable region peptides are provided using the H929 MM cell line and two MM patients.Conclusions and clinical relevanceLC‐MRM assays targeting constant region peptides determine the type and isoform of the involved Ig and quantify its expression; the LC‐MRM approach has improved sensitivity compared with the current clinical method, but slightly higher inter‐assay variability. Detection of variable region peptides is a promising way to improve Ig quantification, which could produce a dramatic increase in sensitivity over existing methods, and could further complement current clinical techniques.
Giant magneto‐impedance effect in thin Finemet nanocrystalline microwires
Authors: Talaat A. , Ipatov M. , Zhukova V. , Blanco J. M. , Churyukanova M. , Kaloshkin S. , Zhukov A. 
Published: April 2014

AbstractWe studied giant magneto‐impedance (GMI) effect, magnetic and structural properties of thin Finemet‐type (FeCuNbSiB) glass‐coated microwires fabricated by Taylor‐Ulitovsky technique with different composition and diameters, with the aim to achieve the optimal conditions for improving the final GMI response. We observed that GMI can be tailored either by controlling the microwires microstructure through the thermal annealing, or by controlling the quenching rate velocity during the fabrication processes. Finally, we obtained up to 50% GMI in the as‐prepared samples and up to 100% in annealed microwires. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hopkinson effect in Co‐rich glass‐coated microwires
Authors: Zhukova V. , Ipatov M. , Talaat A. , Zhukov A. 
Published: April 2014

AbstractWe present studies of the temperature dependence of AC susceptibility, χ, and magnetization, M in few Fe‐Cr based microwires. We observed drastic increasing of the χ in vicinity of Curie temperature which we interpreted as the Hopkinson effect. Cr content drastically affects the Curie temperature of studied microwires. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An almost linear time algorithm for finding Hamilton cycles in sparse random graphs with minimum degree at least three
Authors: Frieze Alan , Haber Simi 
Published: April 2014

AbstractWe describe an algorithm for finding Hamilton cycles in random graphs. Our model is the random graph . In this model G is drawn uniformly from graphs with vertex set [n], m edges and minimum degree at least three. We focus on the case where m = cn for constant c. If c is sufficiently large then our algorithm runs in time and succeeds w.h.p. © 2014 Wiley Periodicals, Inc. Random Struct. Alg., 47, 73–98, 2015
Using modified approaches on marginal regression analysis of longitudinal data with time‐dependent covariates
Authors: Zhou Yi , Lefante John , Rice Janet , Chen Shande 
Published: April 2014

AbstractQuadratic inference functions (QIFs) and estimating equations using the conjugate gradient method (CGM) for fitting marginal models to longitudinal data show appealing features in improving the efficiency without making assumptions on the correlation structure. However, our simulation study shows that both methods produce biased and inefficient estimates of regression parameters when time‐dependent covariates are present. In this paper, we extend both the QIF and CGM methods for fitting marginal models to longitudinal data with time‐dependent covariates. The idea is to restrict the moment conditions to the ones that are only valid to certain types of time‐dependent covariates. Our simulations show that efficiency on estimating regression parameters is achieved using modified approaches. Furthermore, we apply the modified approach to anthropometric screening data to evaluate the association between body mass index and morbidity in children in the Philippines. Copyright © 2014 John Wiley & Sons, Ltd.