bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of susceptibility polymorphisms for nonsyndromic cleft lip with or without cleft palate in the Brazilian population
Authors: de Aquino Sibele Nascimento , Messetti Ana Camila , Hoshi Ryuchi , Borges Andréa , Viena Camila Sane , Reis Sílvia R.A. , Oliveira Swerts Mário Sérgio , Graner Edgard , Martelli‐Júnior Hercílio , Coletta Ricardo D.
Published: January 2014

Background: Although genome‐wide association studies have identified several susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations around the world, the role of most loci is unknown in the highly heterogeneous Brazilian population. Methods: To determine the association of 7 markers that showed genome‐wide significant association in Brazilians with NSCL/P, we conducted a structured association study conditioned upon the individual ancestry proportions to evaluate markers at 1p36 (rs742071), 2p21 (rs7590268), 3p11.1 (rs7632427), 8q21.3 (rs12543318), 13q31.1 (rs8001641), 15q22.2 (rs1873147), and 17q22 (rs227731) in 505 patients with NSCL/P and 594 healthy controls recruited from 2 different geographical regions of Brazil. The polymorphisms were genotyped by TaqMan 5′‐exonuclease allelic discrimination assay, and each sample was independently typed for 40 biallelic short insertion/deletion markers to characterize the genomic ancestry. Results: After Bonferroni correction for multiple tests, significant associations with NSCL/P were observed for rs742071, rs1873147, and rs227731. However, the frequency of the risk alleles varied between the geographical regions, according to the proportions of European and African genomic ancestry. The group enriched by European ancestry showed significant association with rs227731 (p = 0.001), whereas the group with high African ancestry was significantly associated with rs1873147 polymorphism (p = 0.005). The significant association with rs742071 was only detected in the combined sample (p = 0.005). Conclusion: The findings of the present study revealed the associations of 1p36 (rs742071), 15q22 (rs1873147), and 17p22 (rs227731) with NSCL/P in the Brazilian population, and further confirmed that the genetic heterogeneity of NSCL/P may be related to the different ethnic background of the affected individuals. Birth Defects Research (Part A) 100:36–42, 2014. © 2013 Wiley Periodicals, Inc.
Association between maternal COMT gene polymorphisms and fetal neural tube defects risk in a Chinese population
Authors: Liu Jufen , Wang Linlin , Fu Yunting , Li Zhiwen , Zhang Yali , Zhang Le , Jin Lei , Ye Rongwei , Ren Aiguo
Published: January 2014

Background:

Maternal tea consumption was reported to increase the risk of fetal neural tube defects (NTDs). Catechol‐O‐methyltransferase (COMT) may be involved in the metabolism of polyphenolic methylation of tea, thus influence the risk of fetal NTDs. Methods: A total of 576 fetuses or newborns with NTDs and 594 healthy newborns were included in the case–control study. Information on maternal tea consumption, sociodemographic characteristics, reproductive history, and related behavior was collected through face‐to‐face interviews. Maternal blood samples were collected to examine polymorphisms in COMT, and the possible interaction of COMT and tea consumption was analyzed. RESULTS: After controlling for potential confounders, homozygotes of rs737865 showed an elevated risk for total NTDs (odds ratio [OR] = 2.04, 95% confidence interval [CI], 1.24–3.35) and for the anencephaly subtype (OR = 1.99, 95% CI, 1.17–3.39). The CC genotype of rs4633 was positively associated with the overall risk of NTDs (OR = 3.66, 95% CI, 1.05–12.83). Heterozygotes for rs4680 were associated with a decreased risk of spina bifida (OR = 0.71, 95% CI, 0.51–0.98). The COMT rs4680 A allele was negatively related with the risk of spina bifida, with adjusted OR = 0.64 (95% CI, 0.45–0.89). An interaction between tea consumption (1 to 2 cups/day) and the rs4680AA/AG genotype was found in the spina bifida subtype (Pinteraction = .08). Conclusion: Several COMT variants were associated with elevated risk of NTDs in a Chinese population. Maternal tea consumption may be associated with an increased risk for fetal NTDs in genetically susceptible subgroups. Birth Defects Research (Part A) 100:22–29, 2014. © 2013 Wiley Periodicals, Inc.
Epigenetic programing of depression during gestation
Authors: Dulawa Stephanie C.
Published: January 2014

Gestational factors play a role in the development of several neuropsychiatric disorders including schizophrenia and autism. In utero conditions influence future mental health through epigenetic mechanisms, which alter gene expression without affecting DNA coding sequence. Environmental factors account for at least 60% of the risk for developing major depression, and earlier onset of depressive illness has been observed over the past decades. I speculate that gestational factors may play a greater role in programing depression than previously recognized. Here, I examine recent evidence for a role for gestational factors in programing mood disorders, and how epigenetic mechanisms mediate this effect.
Probing Bacterial Uptake of Glycosylated Ciprofloxacin Conjugates
Authors: Milner Stephen J. , Carrick Christopher T. , Kerr Kevin G. , Snelling Anna M. , Thomas Gavin H. , Duhme‐Klair Anne‐Kathrin , Routledge Anne
Published: January 2014

Mono‐ and disaccharide‐functionalised conjugates of the fluoroquinolone antibiotic ciprofloxacin have been synthesised and used as chemical probes of the bacterial uptake of glycosylated ciprofloxacin. Their antimicrobial activities against a panel of clinically relevant bacteria were determined: the ability of these conjugates to inhibit their target DNA gyrase and to be transported into the bacteria was assessed by using in vivo and in vitro assays. The data suggest a lack of active uptake through sugar transporters and that although the addition of monosaccharides is compatible with the inhibition of DNA gyrase, the addition of a disaccharide results in a significant decrease in antimicrobial activity.
Red Fluorescent Turn‐On Ligands for Imaging and Quantifying G Protein‐Coupled Receptors in Living Cells
Authors: Karpenko Iuliia A. , Kreder Rémy , Valencia Christel , Villa Pascal , Mendre Christiane , Mouillac Bernard , Mély Yves , Hibert Marcel , Bonnet Dominique , Klymchenko Andrey S.
Published: January 2014

Classical fluorescence‐based approaches to monitor ligand–protein interactions are generally hampered by the background signal of unbound ligand, which must be removed by tedious washing steps. To overcome this major limitation, we report here the first red fluorescent turn‐on probes for a G protein‐coupled receptor (oxytocin receptor) at the surface of living cells. The peptide ligand carbetocin was conjugated to one of the best solvatochromic (fluorogenic) dyes, Nile Red, which turns on emission when reaching the hydrophobic environment of the receptor. We showed that the incorporation of hydrophilic octa(ethylene glycol) linker between the pharmacophore and the dye minimized nonspecific interaction of the probe with serum proteins and lipid membranes, thus ensuring receptor‐specific turn‐on response. The new ligand was successfully applied for background‐free imaging and quantification of oxytocin receptors in living cells.
Prions: Current Progress in Advanced Research. Edited by Aikikazu Sakudo and Takashi Onodera.
Authors: Pischke Kate E. , Legname Giuseppe
Published: January 2014

Caister Academic, Norwich 2013, VII+137 pp., hardcover, £ 140.00.—ISBN 978‐1‐908230‐24‐9
Cellular and molecular stimulation of adipose‐derived stem cells under hypoxia
Authors: Kang Sangjin , Kim Soo‐Min , Sung Jong‐Hyuk
Published: January 2014

Cultivation under hypoxia has beneficial effects on adipose‐derived stem cells (ASCs). Despite a history of extensive research on the responses of ASCs to hypoxia, investigations have focused on functional alterations of ASCs. Therefore, we provide novel insight in this review into the cellular and molecular changes that occur in ASCs under hypoxic conditions. Hypoxia increases the proliferation and migration of ASCs by the generation of reactive oxygen species (ROS) and downstream phosphorylation of platelet‐derived growth factor receptor‐beta, ERK1/2, and Akt. Chronically, activation of these signaling pathways upregulates miR‐210 via phosphorylation of NF‐κB and Elk1. Protein tyrosine phosphatase, non‐receptor type 2 (PTPN2) is a direct miR‐210 target, and downregulation of PTPN2 mediates the proliferation and migration of ASCs during hypoxia. In addition, the paracrine effect of ASCs is enhanced under hypoxic conditions, irrespective of whether ROS are generated. Hypoxic preconditioning stabilizes hypoxia inducible factor‐1α under hypoxic conditions and increases secretion of vascular endothelial growth factor, thereby improving the regenerative potential of ASCs. Therefore, understanding the cellular and molecular changes that occur during hypoxia is highly relevant for the development of novel ASC therapies.
The case of a migratory fish bone
Authors: Motallebzadeh Reza , Rutter Katharine , Jambulingam Periyathambi
Published: January 2014

Key Clinical Message

We describe a case of a liver abscess due to an ingested foreign body that had migrated through the stomach. Endoscopic removal was performed and laparotomy was avoided.
Immobilized Hydroxynitrile Lyase: A Comparative Study of Recyclability
Authors: Torrelo Guzman , van Midden Nelleke , Stloukal Radek , Hanefeld Ulf
Published: January 2014

Hydroxynitrile lyase from cassava, Manihot esculenta, (MeHNL) catalyzes the formation of (S)‐cyanohydrins from HCN and aldehydes or ketones. Four differently immobilized MeHNLs were prepared: by noncovalent immobilization (celite R‐633), covalent immobilization (cross‐linked enzyme aggregates, CLEA), encapsulation [in a poly(vinyl alcohol) hydrogel Lentikats] and a combination of the above, an unusual immobilization, CLEA encapsulated in a poly(vinyl alcohol) hydrogel. A comparative study of the recyclability of each immobilized MeHNL was performed. Particular attention was paid to the stability and activity of the new immobilized MeHNL–CLEA–Lentikats and to the minimum enzyme loading required to achieve high yields and enantiomeric excesses. MeHNL–CLEA stability was slightly improved by encapsulation into Lentikats and good recyclability rates at low enzyme loading were obtained. However, MeHNL immobilized on celite R‐633 exhibited the best recyclability, giving >95 % conversion and an enantiomeric excess of 99 % during 12 cycles.
Electrochemical‐ and Fluorescent‐Mediated Signal Amplifications for Rapid Detection of Low‐Abundance Circulating Tumor Cells on a Paper‐Based Microfluidic Immunodevice
Authors: Wu Yafeng , Xue Peng , Hui Kam M. , Kang Yuejun
Published: January 2014

The design of a novel paper‐based microfluidic immunodevice with combined electrochemical‐ and fluorescent‐mediated signal amplifications for the highly specific and ultrasensitive point‐of‐care detection of rare circulating tumor cells is reported.
Ordered Hybrids from Template‐Free Organosilane Self‐Assembly
Authors: Chemtob Abraham , Ni Lingli , Croutxé‐Barghorn Céline , Boury Bruno
Published: January 2014

Despite considerable achievements over the last two decades, nonporous organic–inorganic hybrid materials are mostly amorphous, especially in the absence of solvothermal processes. The organosilane self‐assembly approach is one of the few opportunities for creating a regular assembly of organic and inorganic moieties. Additionally, well‐established organosilicon chemistry enables the introduction of numerous organic functionalities. The synthesis of periodically ordered hybrids relies on mono‐, bis‐, or multisilylated organosilane building blocks self‐assembling into hybrid mesostructures or superstructures, subsequently cross‐linked by siloxane Si‐O‐Si condensation. The general synthesis procedure is template‐free and one‐step. However, three concurrent processes underlie the generation of self‐organized hybrid networks: thermodynamics of amphiphilic aggregation, dynamic self‐assembly, and kinetically controlled sol–gel chemistry. Hence, the set of experimental conditions and the precursor structure are of paramount importance in achieving long‐range order. Since the first developments in the mid‐1990s, the subject has seen considerable progress leading to many innovative advanced nanomaterials providing promising applications in membranes, pollutant remediation, catalysis, conductive coatings, and optoelectronics. This work reviews, comprehensively, the primary evolution of this expanding field of research.
Cerium‐Based M4L4 Tetrahedra as Molecular Flasks for Selective Reaction Prompting and Luminescent Reaction Tracing
Authors: Jiao Yang , Wang Jian , Wu Pengyan , Zhao Liang , He Cheng , Zhang Jing , Duan Chunying
Published: January 2014

The application of metal–organic polyhedra as “molecular flasks” has precipitated a surge of interest in the reactivity and property of molecules within well‐defined spaces. Inspired by the structures of the natural enzymatic pockets, three metal–organic neutral molecular tetrahedral, Ce‐TTS, Ce‐TNS and Ce‐TBS (H6TTS: N′,N′′,N′′′‐nitrilotris‐4,4′,4′′‐(2‐hydroxybenzylidene)‐benzohydrazide; H6TNS: N′,N′′,N′′′‐nitrilotris‐6,6′,6′′‐(2‐hydroxybenzylidene)‐2‐naphthohydrazide; H6TBS: 1,3,5‐ phenyltris ‐4,4′,4′′‐(2‐hydroxybenzylidene)benzohydrazide), which exhibit different size of the edges and cavities, were achieved through self‐assembly by incorporating robust amide‐containing tridentate chelating sites into the fragments of the ligands. They acted as molecular flasks to prompt the cyanosilylation of aldehydes with excellent selectivity towards the substrates size. The amide groups worked as trigger sites and catalytic driven forces to achieve efficient guest interactions, enforcing the substrates proximity within the cavity. Experiments on catalysts with the different cavity radii and substrates with the different molecular size demonstrated that the catalytic performance exhibited enzymatical catalytic mechanism and occurred in the molecular flask. These amides were also able to amplify guest‐bonding events into the measurable outputs for the detection of concentration variations of the substrates, providing the possibility for metal–organic hosts to work as smart molecular flasks for the luminescent tracing of catalytic reactions.
Alkylation of Terminal Alkynes with Transient σ‐Alkylpalladium(II) Complexes: A Carboalkynylation Route to Alkyl‐Substituted Alkynes
Authors: Zhou Ming‐Bo , Huang Xiao‐Cheng , Liu Yan‐Yun , Song Ren‐Jie , Li Jin‐Heng
Published: January 2014

A mild and general alkylation of terminal alkynes with transient σ‐alkylpalladium(II) complexes for assembling alkyl‐substituted alkynes is described. This method represents a new way to the use of transient σ‐alkylpalladium(II) complexes in organic synthesis through 1,2‐carboalkynylation of alkenes.
Regeneration of a Conjugated sp2 Graphene System through Selective Defunctionalization of Epoxides by Using a Proven Synthetic Chemistry Mechanism
Authors: Chua Chun Kiang , Pumera Martin
Published: January 2014

Graphene is a promising material capable of driving technological advancement. It is, however, a challenge to obtain pristine graphene in large quantities given the limitation of current synthetic methods. Among the numerous methods available, the chemical approach provides an optimistic outlook and has garnered much interest within the graphene community as a potential alternative. One of the most crucial steps of the chemical approach is the chemical reduction of graphene oxide as this dictates the final quality of the graphene sheets. In recent years, much of the focus has shifted to the usage of established reducing agents or oxygen removal reagents, frequently applied in organic chemistry, onto a graphene oxide platform. Herein, the selective removal of epoxide groups and subsequent regeneration of disrupted conjugated sp2 system is highlighted, based on the synergistic effect of indium and indium(I) chloride. The morphological, structural, and electrical properties of the resulting graphene were fully characterized with X‐ray photoelectron, Fourier transform IR, solid‐state 13C NMR, and Raman spectroscopy; thermogravimetric analysis; scanning electron microscopy; and conductivity measurements. The as‐prepared graphene showed a tenfold increase in conductivity against conventional graphene treated with hydrazine reducing agent and demonstrated a high dispersion stability in ethanol. Moreover, the selective defunctionalization of the epoxide groups provides opportunities for potential tailoring of graphene properties for prospective applications.
Obesity‐associated gastrointestinal tract cancer: From beginning to end
Authors: Berger Nathan A.
Published: January 2014

Unique aspects of the newly reported association between obesity and oral squamous cell carcinoma of the tongue are addressed in view of the current obesity pandemic and its relation to an increased risk of cancer incidence and worse cancer prognosis. Attention is called to problems evaluating and treating cancer in the presence of obesity. Potential biologic links are discussed, including: 1) increased sex steroid hormones; 2) increased growth factors; 3) altered adipokine levels; 4) low‐grade inflammation; and 5) altered microbiomes. Concern is raised regarding the potential interaction between human papillomavirus and obesity, each of which is now associated with an increased relative risk of cancer of the tongue.
Novozym 435‐Catalyzed Syntheses of Polyesters and Polyamides of Medicinal and Industrial Relevance
Authors: Khan Abdullah , Sharma Sunil K. , Kumar Amit , Watterson Arthur C. , Kumar Jayant , Parmar Virinder S.
Published: January 2014

The adverse impact of chemical and biochemical waste on the environment and human health poses a serious challenge in today’s World. The best way to address these challenges is to reduce the waste by developing more efficient processes and technologies, based on the principles of “green chemistry”. Some of these synthetic approaches involving the chemoenzymatic synthetic methodologies are discussed herein. These lead to the formation of unique nanomaterials with diverse applications, such as drugs/gene delivery systems, flame retardant materials, conducting polymers, controlled release systems, diagnostic agents, and polymeric electrolytes for nanocrystalline solar cells.
Cleavage of CO Bonds in Lignin Model Compounds Catalyzed by Methyldioxorhenium in Homogeneous Phase
Authors: Harms Reentje G. , Markovits Iulius I. E. , Drees Markus , Herrmann h.c. mult. Wolfgang A. , Cokoja Mirza , Kühn Fritz E.
Published: January 2014

Methyldioxorhenium (MDO)‐catalyzed CO bond cleavage of a variety of lignin β‐O‐4‐model compounds yields phenolic and aldehydic compounds in homogeneous phase under mild reaction conditions. MDO is in situ generated by reduction of methyltrioxorhenium (MTO) and is remarkably stable under the applied reaction conditions allowing its reuse for least five times without significant activity loss. Based on the observed and isolated intermediates, 17 O‐ and 2 H‐isotope labeling experiments, DFT calculations, and several spectroscopic studies, a reaction mechanism is proposed.
Biosourced Nitrogen‐Doped Microcellular Carbon Monoliths
Authors: Brun Nicolas , Osiceanu Petre , Titirici Magdalena M.
Published: January 2014

An original approach based on the hydrothermal carbonization of nitrogen‐containing biomass derivatives within the continuous phase of a direct concentrated emulsion is reported for the synthesis of nitrogen‐doped microcellular carbon monoliths. These biosourced foams show promising performances as intrinsic electrocatalysts in the oxygen reduction reaction. Preliminary catalytic properties of powdered versus monolithic samples are discussed and suggest interesting prospects for their introduction within electrochemical devices.
The receptor‐like kinases GSO1 and GSO2 together regulate root growth in arabidopsis through control of cell division and cell fate specification
Authors: Racolta Adriana , Bryan Anthony C. , Tax Frans E.
Published: January 2014

COVER PHOTOGRAPH: Confocal image of a median optical section through a heart stage Arabidopsis embryo expressing the epidermalmarker pATML1:: HTA6‐GFP and counterstained with propidium iodide. From The receptor‐like kinases GSO1 and GSO2 together regulate root growth in Arabidopsis through control of cell division and cell fate specification; Racolta et al, Developmental Dynamics 243:257–278.
Increasing pCO2 correlates with low concentrations of intracellular dimethylsulfoniopropionate in the sea anemone Anemonia viridis
Authors: Borell Esther M. , Steinke Michael , Horwitz Rael , Fine Maoz
Published: January 2014

Marine anthozoans maintain a mutualistic symbiosis with dinoflagellates that are prolific producers of the algal secondary metabolite dimethylsulfoniopropionate (DMSP), the precursor of the climate‐cooling trace gas dimethyl sulfide (DMS). Surprisingly, little is known about the physiological role of DMSP in anthozoans and the environmental factors that regulate its production. Here, we assessed the potential functional role of DMSP as an antioxidant and determined how future increases in seawater pCO2 may affect DMSP concentrations in the anemone Anemonia viridis along a natural pCO2 gradient at the island of Vulcano, Italy. There was no significant difference in zooxanthellae genotype and characteristics (density of zooxanthellae, and chlorophyll a) as well as protein concentrations between anemones from three stations along the gradient, V1 (3232 μatm CO2), V2 (682 μatm) and control (463 μatm), which indicated that A. viridis can acclimate to various seawater pCO2. In contrast, DMSP concentrations in anemones from stations V1 (33.23 ± 8.30 fmol cell−1) and V2 (34.78 ± 8.69 fmol cell−1) were about 35% lower than concentrations in tentacles from the control station (51.85 ± 12.96 fmol cell−1). Furthermore, low tissue concentrations of DMSP coincided with low activities of the antioxidant enzyme superoxide dismutase (SOD). Superoxide dismutase activity for both host (7.84 ± 1.37 U·mg−1 protein) and zooxanthellae (2.84 ± 0.41 U·mg−1 protein) at V1 was 40% lower than at the control station (host: 13.19 ± 1.42; zooxanthellae: 4.72 ± 0.57 U·mg−1 protein). Our results provide insight into coastal DMSP production under predicted environmental change and support the function of DMSP as an antioxidant in symbiotic anthozoans.
Phosphane‐Ligated Ionic Palladium Complexes: Synthesis, Characterization and Application as Efficient and Reusable Precatalysts for the Homogeneous Carbonylative Sonogashira Reaction under CuI‐Free Conditions
Authors: Zhang Jing , Wang Yongyong , Zhao Xiaoli , Liu Ye
Published: January 2014

The stable ionic PdII complexes 1A–4A were synthesized through the complexation of PdCl2(MeCN)2 with the phosphane‐functionalized ionic liquids (FILs) 1–4 with π‐acceptor character. Single‐crystal X‐ray diffraction analyses showed that 1A–4A were all composed of PdII‐centred square‐planar cations and triflate (OTf–, CF3SO3–) counteranions. The complex cations in 1A–3A possessed structural similarity to trans‐PdCl2(PPh3)2. The cation in 4A was a new PdII‐centered planar complex ligated by the phosphane–carbon anion–carbene (PCC) pincer in a tripodal manner. The stabilities of 1A–4A were improved due to the intensive π‐backbonding interaction between the Pd and P atoms. When complexes 1A–4A were used as precatalysts for homogeneous carbonylative Sonogashira coupling of PhI with phenylacetylene free of CuI, 1A–3A exhibited excellent catalytic behaviour with a TON of up to 1700 at a CO pressure of 0.5 MPa and moderate temperature of 100 °C, whereas 4A exhibited poor activity towards the transformation of PhI due to the high stability of 4A. The recycling experiments of 3A in [Bpy]BF4 (as a solvent) indicated that 3A could be recycled for 5 runs with neither activity loss nor metal leaching into the organic phase. Complex 3A also proved to be a general precatalyst for the carbonylative Sonogashira couplings of a wide range of aryl iodides with phenylacetylene. The selectivity of the desired carbonylation product depended more on electronic effects than the steric effects of the substituents of the aryl iodides.
A validated method for the determination of nucleotides in infant formulas by capillary electrophoresis coupled to mass spectrometry
Authors: Rodríguez‐Gonzalo Encarnación , Domínguez‐Álvarez Javier , Mateos‐Vivas María , García‐Gómez Diego , Carabias‐Martínez Rita
Published: January 2014

In this work CE‐ESI‐MS is proposed for the identification and simultaneous quantification of several ribonucleotide 5′‐monophosphates in infant formula (IF) samples. The target compounds were adenosine 5′‐monophosphate, cytidine 5′‐monophosphate, guanosine 5′‐monophosphate, uridine 5′‐monophosphate, and inosine 5′‐monophosphate. To our knowledge, the application of CE for the determination of these bioactive compounds in IFs has not yet been described. Optimization of the composition of the electrophoretic separation buffer and ‐mainly‐ the injection medium was carried out with a view to obtaining the best sensitivity and separation efficiency for the CE‐MS coupling. Different sample treatments were assayed and one based on centrifugal ultrafiltration proved to be the simplest and most compatible with CE separation of the analytes and their ionization by the electrospray source. The whole optimized method (centrifugal ultrafiltration treatment prior to CE‐MS) was validated according to the 2002/657/EC decision, obtaining a reliable and robust CE‐MS method to determine these compounds in IF samples, with LODs between 0.8 and 1.8 μg/g (S/N = 3) and recoveries in the 90–106% range.
Measurement error in two‐stage analyses, with application to air pollution epidemiology
Authors: Szpiro Adam A. , Paciorek Christopher J.
Published: January 2014

Public health researchers often estimate health effects of exposures (e.g., pollution, diet, and lifestyle) that cannot be directly measured for study subjects. A common strategy in environmental epidemiology is to use a first‐stage (exposure) model to estimate the exposure on the basis of covariates and/or spatiotemporal proximity and to use predictions from the exposure model as the covariate of interest in the second‐stage (health) model. This induces a complex form of measurement error. We propose an analytical framework and methodology that is robust to misspecification of the first‐stage model and provides valid inference for the second‐stage model parameter of interest.

We decompose the measurement error into components analogous to classical and Berkson errors and characterize properties of the estimator in the second‐stage model if the first‐stage model predictions are plugged in without correction. Specifically, we derive conditions for compatibility between the first‐stage and second‐stage models that guarantee consistency (and have direct and important real‐world design implications), and we derive an asymptotic estimate of finite‐sample bias when the compatibility conditions are satisfied. We propose a methodology that does the following: (i) corrects for finite‐sample bias; and (ii) correctly estimates standard errors. We demonstrate the utility of our methodology in simulations and an example from air pollution epidemiology. Copyright © 2013 John Wiley & Sons, Ltd.
Detailed analysis of a smouldering fire scenario at the murder scene experimental and numerical investigations
Authors: Hofmann Anja , Knaust Christian , Krüger Simone , Raspe Tina , Deubel Jan H.
Published: January 2014

Based on forensic evidence, a smouldering fire was observed to have occurred at a murder scene. Identification of a reasonable timeline – specifically the fire dynamics of the ignition and fire growth that occurred coincident with the death that took place – became an important focus of the criminal investigation that followed. The fire service was called when a neighbour saw a grey smoke escaping through the ventilation system of the bathrooms on the roof of the house. One flat door with elevated temperatures was found. The fire fighter who entered the flat first reported later that the flat was completely filled with smoke and all windows were closed. When the fire fighter opened the balcony door, he saw flames on the sofa that he extinguished. Then he found a body on the floor. The autopsy showed later that the victim was dead before the fire started. The police suspected that the murderer probably had deliberately set the fire to destroy evidence. One suspect had been witnessed to be in the flat approximately 2 h before the fire was detected by the neighbour. The aim of this project was to investigate how the fire most likely started and developed. Copyright © 2014 John Wiley & Sons, Ltd.
Genome‐wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in East Asians
Authors: Zhang Ben , Jia Wei‐Hua , Matsuo Keitaro , Shin Aesun , Xiang Yong‐Bing , Matsuda Koichi , Jee Sun Ha , Kim Dong‐Hyun , Cheah Peh Yean , Ren Zefang , Cai Qiuyin , Long Jirong , Shi Jiajun , Wen Wanqing , Yang Gong , Ji Bu‐Tian , Pan Zhi‐Zhong , Matsuda Fumihiko , Gao Yu‐Tang , Oh Jae Hwan , Ahn Yoon‐Ok , Kubo Michiaki , Thean Lai Fun , Park Eun Jung , Li Hong‐Lan , Park Ji Won , Jo Jaeseong , Jeong Jin‐Young , Hosono Satoyo , Nakamura Yusuke , Shu Xiao‐Ou , Zeng Yi‐Xin , Zheng Wei
Published: January 2014

Genome‐wide association studies (GWAS) of colorectal cancer (CRC) have been conducted primarily in European descendants. In a GWAS conducted in East Asians, we first analyzed approximately 1.7 million single‐nucleotide polymorphisms (SNPs) in four studies with 1,773 CRC cases and 2,642 controls. We then selected 66 promising SNPs for replication and genotyped them in three independent studies with 3,612 cases and 3,523 controls. Five SNPs were further evaluated using data from four additional studies including up to 3,290 cases and 4,339 controls. SNP rs7229639 in the SMAD7 gene was found to be associated with CRC risk with an odds ratio (95% confidence interval) associated with the minor allele (A) of 1.22 (1.15–1.29) in the combined analysis of all 11 studies (p = 2.93 × 10−11). SNP rs7229639 is 2,487 bp upstream from rs4939827, a risk variant identified previously in a European‐ancestry GWAS in relation to CRC risk. However, these two SNPs are not correlated in East Asians (r2 = 0.008) nor in Europeans (r2 = 0.146). The CRC association with rs7229639 remained statistically significant after adjusting for rs4939827 as well as three additional CRC risk variants (rs58920878, rs12953717 and rs4464148) reported previously in this region. SNPs rs7229639 and rs4939827 explained approximately 1% of the familial relative risk of CRC in East Asians. This study identifies a new CRC risk variant in the SMAD7 gene, further highlighting the significant role of this gene in the etiology of CRC.
Biembedding Steiner Triple Systems in Surfaces Using the Bose Construction
Authors: Griggs T. S. , Psomas C. , Širáň J.
Published: January 2014

A uniform framework is presented for biembedding Steiner triple systems obtained from the Bose construction using a cyclic group of odd order, in both orientable and nonorientable surfaces. Within this framework, in the nonorientable case, a formula is given for the number of isomorphism classes and the particular biembedding of Ducrocq and Sterboul (preprint 18pp., 1978) is identified. In the orientable case, it is shown that the biembedding of Grannell et al. (J Combin Des6(), 325–336) is, up to isomorphism, the unique biembedding of its type. Automorphism groups of the biembeddings are also given.
Smad6 Suppresses the Growth and Self‐Renewal of Hepatic Progenitor Cells
Authors: Ding Ze‐Yang , Liang Hui‐Fang , Jin Guan‐Nan , Chen Wei‐Xun , Wang Wei , Datta Pran K. , Zhang Ming‐Zhi , Zhang Bixiang , Chen Xiao‐Ping
Published: January 2014

Activation of hepatic progenitor cells (HPCs) is commonly observed in chronic liver disease and Wnt/β‐catenin signaling plays a crucial role in the expansion of HPCs. However, the molecular mechanisms that regulate the activation of Wnt/β‐catenin signaling in the liver, especially in HPCs, remain largely elusive. Here, we reported that ectopic expression of Smad6 suppressed the proliferation and self‐renewal of WB‐F344 cells, a HPC cell line. Mechanistically, we found that Smad6 inhibited Wnt/β‐catenin signaling through promoting the interaction of C‐terminal binding protein (CtBP) with β‐catenin/T‐cell factor (TCF) complex to inhibit β‐catenin mediated transcriptional activation in WB‐F344 cells. We used siRNA targeting β‐catenin to demonstrate that Wnt/β‐catenin signaling was required for the proliferation and self‐renewal of HPCs. Taken together, these results suggest that Smad6 is a regulatory molecule which regulates the proliferation, self‐renewal and Wnt/β‐catenin signaling in HPCs. J. Cell. Physiol. 229: 651–660, 2014. © 2013 Wiley Periodicals, Inc.
Modeling of 24‐hour glucose and insulin profiles in patients with type 2 diabetes mellitus treated with biphasic insulin aspart
Authors: Røge Rikke M. , Klim Søren , Kristensen Niels R. , Ingwersen Steen H. , Kjellsson Maria C.
Published: January 2014

Insulin therapy for diabetes patients is designed to mimic the endogenous insulin response of healthy subjects and thereby generate normal blood glucose levels. In order to control the blood glucose in insulin‐treated diabetes patients, it is important to be able to predict the effect of exogenous insulin on blood glucose. A pharmacokinetic/pharmacodynamic model for glucose homoeostasis describing the effect of exogenous insulin would facilitate such prediction. Thus the aim of this work was to extend the previously developed integrated glucose–insulin (IGI) model to predict 24‐hour glucose profiles for patients with Type 2 diabetes following exogenous insulin administration. Clinical data from two trials were included in the analysis. In both trials, 24‐hour meal tolerance tests were used as the experimental setup, where exogenous insulin (biphasic insulin aspart) was administered in relation to meals. The IGI model was successfully extended to include the effect of exogenous insulin. Circadian variations in glucose homeostasis were assessed on relevant parameters, and a significant improvement was achieved by including a circadian rhythm on the endogenous glucose production in the model. The extended model is a useful tool for clinical trial simulation and for elucidating the effect profile of new insulin products.
Orientable Hamilton Cycle Embeddings of Complete Tripartite Graphs II: Voltage Graph Constructions and Applications
Authors: Ellingham M. N. , Schroeder Justin Z.
Published: January 2014

In an earlier article the authors constructed a hamilton cycle embedding of in a nonorientable surface for all and then used these embeddings to determine the genus of some large families of graphs. In this two‐part series, we extend those results to orientable surfaces for all . In part II, a voltage graph construction is presented for building embeddings of the complete tripartite graph on an orientable surface such that the boundary of every face is a hamilton cycle. This construction works for all such that p is prime, completing the proof started by part I (which covers the case ) that there exists an orientable hamilton cycle embedding of for all , . These embeddings are then used to determine the genus of several families of graphs, notably for and, in some cases, for .
Analysis of new biomarkers for cholangiocarcinoma
Authors: Miwa Masanao , You Gyokukou , Tanaka Hideaki , Taniguchi Seigo , Fujii Takahiro , Kamemura Kazuo , Suzaki Masafumi , Isono Takahiro , Tooyama Ikuo , Tanaka Masakazu , Srivatanakul Petcharin , Viwatthanasittiphong Chutiwan , Sangrajrang Suleeporn , Khuhaprema Thiravud
Published: January 2014

Cholangiocarcinoma is one of the most serious diseases in northeast Thailand, where its incidence is reported to be the highest in the world. We tried to develop a new method to detect cholangiocarcinoma in the early stages using serum proteins. We found that after fluorescent labeling of the sugar moiety of serum proteins, a new peak was identified, which might be a promising marker for cholangiocarcinoma.
Spectroscopic studies on the interaction mechanisms of safranin T with herring sperm DNA using acridine orange as a fluorescence probe
Authors: Long Jun , Wang Xing‐ming , Xu Dong‐ling , Ding Li‐sheng
Published: January 2014

Under the condition of physiological pH environment (pH = 7.40), the interactions of safranin T (ST) with herring sperm DNA were studied by means of spectral methods using acridine orange (AO) as a fluorescence probe. The spectroscopic characteristics of DNA–AO in the case of ST (along with the increase of concentration) were observed in an aqueous medium. The binding constants for ST stranded DNA and competitive bindings of ST interacting with DNA–AO systems were examined by fluorescence spectra, and the binding mechanism of ST with DNA was researched via viscosity measurements. All the testimony manifested that bonding modes between ST and DNA were evidenced to be intercalative binding and electrostatic binding, and the combining constant of ST with DNA was obtained. The binding of ST to DNA was driven by entropy and enthalpy through the calculated thermodynamic parameters (ΔrHmӨ, ΔrSm and ΔrGmӨ). Copyright © 2014 John Wiley & Sons, Ltd.
Molecular dynamics simulation studies for DNA sequence recognition by reactive metabolites of anticancer compounds
Authors: Tumbi Khaled M. , Nandekar Prajwal P. , Shaikh Naeem , Kesharwani Siddharth S. , Sangamwar Abhay T.
Published: January 2014

The discovery of novel anticancer molecules 5F‐203 (NSC703786) and 5‐aminoflavone (5‐AMF, NSC686288) has addressed the issues of toxicity and reduced efficacy by targeting over expressed Cytochrome P450 1A1 (CYP1A1) in cancer cells. CYP1A1 metabolizes these compounds into their reactive metabolites, which are proven to mediate their anticancer effect through DNA adduct formation. However, the drug metabolite–DNA binding has not been explored so far. Hence, understanding the binding characteristics and molecular recognition for drug metabolites with DNA is of practical and fundamental interest. The present study is aimed to model binding preference shown by reactive metabolites of 5F‐203 and 5‐AMF with DNA in forming DNA adducts. To perform this, three different DNA crystal structures covering sequence diversity were selected, and 12 DNA‐reactive metabolite complexes were generated. Molecular dynamics simulations for all complexes were performed using AMBER 11 software after development of protocol for DNA‐reactive metabolite system. Furthermore, the MM‐PBSA/GBSA energy calculation, per‐nucleotide energy decomposition, and Molecular Electrostatic Surface Potential analysis were performed. The results obtained from present study clearly indicate that minor groove in DNA is preferable for binding of reactive metabolites of anticancer compounds. The binding preferences shown by reactive metabolites were also governed by specific nucleotide sequence and distribution of electrostatic charges in major and minor groove of DNA structure. Overall, our study provides useful insights into the initial step of mechanism of reactive metabolite binding to the DNA and the guidelines for designing of sequence specific DNA interacting anticancer agents. Copyright © 2014 John Wiley & Sons, Ltd.
Three‐dimensional through‐time radial GRAPPA for renal MR angiography
Authors: Wright Katherine L. , Lee Gregory R. , Ehses Philipp , Griswold Mark A. , Gulani Vikas , Seiberlich Nicole
Published: January 2014

Purpose

To achieve high temporal and spatial resolution for contrast‐enhanced time‐resolved MR angiography exams (trMRAs), fast imaging techniques such as non‐Cartesian parallel imaging must be used. In this study, the three‐dimensional (3D) through‐time radial generalized autocalibrating partially parallel acquisition (GRAPPA) method is used to reconstruct highly accelerated stack‐of‐stars data for time‐resolved renal MRAs.

Materials and Methods

Through‐time radial GRAPPA has been recently introduced as a method for non‐Cartesian GRAPPA weight calibration, and a similar concept can also be used in 3D acquisitions. By combining different sources of calibration information, acquisition time can be reduced. Here, different GRAPPA weight calibration schemes are explored in simulation, and the results are applied to reconstruct undersampled stack‐of‐stars data.

Results

Simulations demonstrate that an accurate and efficient approach to 3D calibration is to combine a small number of central partitions with as many temporal repetitions as exam time permits. These findings were used to reconstruct renal trMRA data with an in‐plane acceleration factor as high as 12.6 with respect to the Nyquist sampling criterion, where the lowest root mean squared error value of 16.4% was achieved when using a calibration scheme with 8 partitions, 16 repetitions, and a 4 projection × 8 read point segment size.

Conclusion

3D through‐time radial GRAPPA can be used to successfully reconstruct highly accelerated non‐Cartesian data. By using in‐plane radial undersampling, a trMRA can be acquired with a temporal footprint less than 4s/frame with a spatial resolution of approximately 1.5 mm × 1.5 mm × 3 mm. J. Magn. Reson. Imaging 2014;40:864–874. © 2014 Wiley Periodicals, Inc.
Antimicrobial potentials of active component isolated from Citrullus colocynthis fruits and structure–activity relationships of its analogues against foodborne bacteria
Authors: Kim Min‐Gi , Lee Sung‐Eun , Yang Ji‐Yeon , Lee Hoi‐Seon
Published: January 2014

BACKGROUND

Synthetic preservatives have been consistently used to maintain the quality of food products. However, the degree of danger to human health cannot be ignored. In this study, the antimicrobial activities of Citrullus colocynthis fruits and 4‐methylquinoline analogues were investigated to develop natural preservatives against foodborne bacteria.

RESULTS

Antimicrobial activities of the methanol extract and five fractions derived from C. colocynthis fruits were evaluated against five foodborne bacteria. The chloroform fraction possessed strong activities against five foodborne bacteria. 4‐Methylquinoline was isolated by chromatographic analyses. To establish the structure–activity relationships, the antimicrobial activities of 4‐methylquinoline analogues (2‐hydroxyquinoline, 4‐hydroxyquinoline, 6‐hydroxyquinoline, 2‐methylquinoline, 6‐methyquinoline, 8‐methylquinoline and 2‐methyl‐8‐hydroxyquinoline) were tested against food‐borne bacteria. When employing the agar diffusion method, 2‐methyl‐8‐hydroxyquinoline was found to have potent activities against the five foodborne bacteria. In terms of minimum bactericidal concentration or minimum inhibitory concentration, 2‐methyl‐8‐hydroxyquinoline had significantly higher antimicrobial activity against the five foodborne bacteria.

CONCLUSION

Citrullus colocynthis fruits and 4‐methylquinoline analogues could be useful for the development of eco‐friendly food supplemental agents and pharmaceuticals. © 2014 Society of Chemical Industry
Prognostic significance of lymph node status in patients with metastatic colorectal carcinoma treated with lymphadenectomy
Authors: Liu Yan‐Long , Xu Hai‐tao , Jiang Shi‐Xiong , Yang Yan‐Mei , Cui Bin‐Bin
Published: January 2014

Background and Objectives

To test prognostic significance of lymph node status in patients with metastatic colorectal carcinoma (mCRC).

Methods

Four hundred ninety six patients diagnosed with synchronous mCRC and treated with lymphadenectomy between 1995 and 2008 were identified and divided into groups pN0, pN1, and pN2 (140 (28.2%) in pN0, 223 (45.0%) in pN1, and 133 (26.8%) in pN2 group) according to their lymph node status. The Kaplan–Meier and Cox regression analyses were used to test associations and independent predictor status of lymph node involvement.

Results

The Cox proportional hazards regression showed pN as significantly associated with disease‐specific survival (DSS) both in univariate (HR = 1.609, 95% CI 1.411 to 1.835, P < 0.001) and multivariate (HR = 1.630, 95% CI 1.422 to 1.868, P < 0.001) analyses. The Kaplan–Meier analysis demonstrated that patients with pN2 and pN1 had a significantly worse DSS compared with patients with pN0 tumors (respectively, 17.273 ± 1.020 and 27.145 ± 1.715 vs. 34.992 ± 2.143 months; P < 0.001). In accuracy analyses based on AUC values, nodal status demonstrated the highest accuracy (65.1%) out of all the variables.

Conclusions

Our findings indicate that optimal TNM staging for mCRC should incorporate lymph node status to provide a more effective and predictive model. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
Selective extraction of clonazepam from human plasma and urine samples by molecularly imprinted polymeric beads
Authors: Panahi Homayon Ahmad , Mehramizi Ali , Ghassemi Somayeh , Moniri Elham
Published: January 2014

A molecularly imprinted polymer (MIP) based on free‐radical polymerization was prepared with 1‐(N,N‐biscarboxymethyl)amino‐3‐allylglycerol andN,N‐dimethylacrylamide as functional monomers,N,N‐methylene diacrylamide as the cross‐linker, copper ion‐clonazepam as the template and 2,2‐azobis(2‐methylbutyronitrile) as the initiator. The imprinted polymer was characterized byFourier transform infrared spectroscopy, elemental analysis, thermogravimetric analysis, andSEM. TheMIPof agglomerated microparticles with multipores was used forSPE. The imprinted polymer sorbent was selective for clonazepam. The optimum pH and sorption capacity were 5 and 0.18 mg/g at 20°C, respectively. The profile of the drug uptake by the sorbent reflects good accessibility of the active sites in the imprinted polymer sorbent. TheMIP‐SPEwas the most feasible technique for the extraction of clonazepam with a high recovery from human plasma and urine samples.
Metabolism of TM‐2, a potential antitumor drug, in rats by using LC–MS
Authors: Men Lei , Lin Hongli , Zhao Yunli , Liu Hui , Yang Mingjing , Fan Ronghua , Wang Pei , Tang Xing , Yu Zhiguo
Published: January 2014

TM‐2 (13‐(N‐Boc‐3‐i‐butylisoserinoyl‐4,10‐β‐diacetoxy‐2‐α‐benzoyloxy‐5‐β‐20‐epoxy‐1,13‐α‐dihydroxy‐9‐oxo‐19‐norcyclopropa[g]tax‐11‐ene) is a novel semisynthetic taxane derivative. Our previous study suggested that TM‐2 is a promising antitumor analogue. In this paper, the metabolism of TM‐2 was investigated in rats following intravenous administration. Two different types of mass spectrometry—hybrid linear trap quadrupole orbitrap (LTQ‐Orbitrap) mass spectrometry and triple‐quadrupole tandem (QQQ) mass spectrometry—were employed to acquire structural information of TM‐2 metabolites. A total of 17 components were identified as the metabolites of TM‐2 in bile, feces, and urine samples. Accurate mass measurement using LC–LTQ‐Orbitrap‐MS was used to determine the accurate mass data and elemental composition of metabolites thereby confirming the proposed structures of the metabolites. The metabolites proposed were mainly oxidates of TM‐2, including methoxy, hydroxyl, dihydroxy, and trihydroxyl analogues. The major metabolic pathway of TM‐2 was the hydroxylation of the taxane ring or the lateral chain. These important metabolic data serve as a useful resource to support further research of TM‐2.