bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Genetics of Congenital Myasthenic Syndromes
Authors: Ohno Kinji , Ohkawara Bisei , Ito Mikako , Engel Andrew G
Published: May 2014

Congenital myasthenic syndromes (CMS) are heterogeneous disorders caused by congenital defects of molecules expressed at the neuromuscular junctions. Clinical features include fatigable muscle weakness, amyotrophy and minor facial anomalies. Mutations have been identified in 18 genes encoding acetylcholine receptor (AChR) subunits (CHRNA1,CHRNB1,CHRNDandCHRNE); skeletal muscle sodium channel (SCN4A); signalling molecules driving AChR clustering and subserving maintenance and differentiation of the postsynaptic region (AGRN, LRP4, MUSKandDOK7); postsynaptic structural proteins (RAPSNandPLEC); synaptic β2 laminin, which promotes presynaptic differentiation, and synaptic collagen Q; presynaptic choline acetyltransferase and enzymes in subserving protein glycosylation (GFPT1,DPAGT1,ALG14, andALG2). The CMS are caused by recessive mutations except for the slow‐channel CMS. The recent development of the exome sequencing has speeded identification of causative mutations. Mutations in glycosylation genes were recently discovered, but the mechanisms by which they impair neuromuscular signal transmission have not been fully elucidated.

Key Concepts:

Congenital myasthenic syndromes are caused by germline mutations in molecules expressed at the neuromuscular junction (NMJ).

Muscle nicotinic acetylcholine receptor (AChR) is a pentameric ligand‐gated ion channel in the stoichiometry of α2βδϵ subunits.

Missense mutations in AChR subunit genes can cause abnormally long and brief ion channel openings resulting in slow‐ and fast‐channel myasthenic syndromes, respectively.

Primary endplate AChR deficiency can be due to low‐expressor or null mutations in the AChR ϵ subunit. The phenotype in case of biallelic low‐expressor or null mutations in the ϵ subunit is rescued by expression of the foetal γ subunit. Biallelic null mutations in non‐ϵ are embryonic lethal mutations.

A second group of endplate AChR deficiency is caused by mutations in signalling molecules including agrin, LRP4, MuSK, Dok‐7, which drive AChR clustering.

The third group of endplate AChR deficiency stems from mutations in the postsynaptic structural proteins of rapsyn or plectin.

Mutations in enzymes subserving theN‐glycosylation pathway of GFPT1, DPAGT1, ALG14 and ALG2 cause limb‐girdle CMS with tubular aggregates.

Endplate acetylcholinesterase (AChE) deficiency is caused by mutations in collagen Q (ColQ), which anchors AChE to the synaptic basal lamina.

Protein‐anchoring therapy, in which ectopically expressed AChE/ColQ complex is specifically anchored to the neuromuscular junction using the proprietary binding motifs, markedly ameliorates myasthenic symptoms ofColq‐knockout mice.

Mutations in choline acetyltransferase (ChAT) cause defective resynthesis of ACh at the nerve terminal and a CMS associated with frequent episodic apnoea.
Molecular Genetics of Oral Cancer
Authors: Sand Lars
Published: May 2014

Oral squamous cell carcinoma (OSCC) is the most common epithelial malignancy in the oral cavity and constitutes more than 90% of oral malignancies. OSCC is a complex malignancy where environmental factors, viral infections and genetic alterations most likely interact, and thus give rise to the malignant condition. Epidemiological investigations have shown that heavy tobacco smoking, high alcohol consumption and human papilloma virus infection are the major risk factors for OSCC development. These factors interact with specific genes important for normal cellular development and genetic alterations may finally lead to a malignant phenotype. Genetic mutations accumulated over time are needed for an oral cancer to develop and several molecular genetic changes have been associated with the development of OSCC. The most important genetic alterations associated with the condition are tumour suppressor genes, oncogenes, epigenetic changes, genomic instability, mitochondrial mutations, microRNAs and loss of heterozygosity.

Key Concepts:

Oral cancer is caused by extrinsic and/or intrinsic factors.

Loss of heterozygosity is an important event in oral carcinogenesis.

Mutated
p53
is a common event in OSCC.

Telomere length is maintained in some OSCC.

mtDNA is involved in OSCC.

Epigenetic changes seem to be an early event in oral carcinogenesis.

miRNA may be aberrant in OSCC.
Molecular Genetics of Argininosuccinic Aciduria
Authors: Trevisson Eva , Doimo Mara , Salviati Leonardo
Published: May 2014

Argininosuccinic aciduria is an autosomal recessive disorder of the urea cycle caused by mutations in argininosuccinate lyase (ASL). Two main clinical phenotypes are reported: an acute neonatal form characterised by severe hyperammonaemia and coma, and a subacute, late‐onset form which may present with relatively milder neurological symptoms.

More than 120ASLmutations have been reported so far: the majority are missense, but virtually all types of point mutations are found. Large rearrangements are rare and standard genomicdeoxyribonucleic acid (DNA)analysis has a high diagnostic yield.

Genotype–phenotype correlations have been difficult to establish as standard biochemical techniques are not sufficiently sensitive to measure residual activity, and other factors such as intragenic complementation, overexpression of nonfunctionalASLtranscripts and environmental factors may modulate the phenotype.

Clinical manifestations result from the block in the urea cycle and also from impairment of nitric oxide biosynthesis, and the therapy is aimed at restoring these two functions.

Key Concepts:

Argininosuccinic aciduria is caused by deficiency of argininosuccinate lyase (ASL).

ASL is a component of the urea cycle and is essential for detoxification of ammonia, and for the synthesis of arginine and nitric oxide (NO).

Two clinical forms of argininosuccinic aciduria exist: an acute, potentially lethal, neonatal onset disease and a milder, late‐onset form.

More than 120 ASL mutations have been described but the exact genotype/phenotype correlations are still not completely clear.

Other factors (genetic and environmental) may influence the clinical phenotype.

Treatment is based on protein restriction, arginine, nitrogen scavengers and NO donors.
Unexpected Positive Events Do Not Result in Flashbulb Memories
Authors: Kraha Amanda , Talarico Jennifer M. , Boals Adriel
Published: May 2014

The study of flashbulb memories has typically been confined to negative events such as the terrorist attacks of 11 September 2001. Previous studies that investigated the role of affect on memory formation have produced conflicting results, making it difficult to ascertain the properties of positive flashbulb memories. In the current study, we employ previously established methods to investigate flashbulb memory formation for the assassination of Osama bin Laden. This resonated as a highly positive event for many Americans evidenced by the thousands of people flooding the streets of Washington, D.C., and New York City to celebrate. Results confirm the fading of memory details over time and further suggest that positive events do not result in the heightened vividness and confidence seen in negatively valenced flashbulb memories. We argue that these findings are additional evidence against a special memory mechanism in flashbulb memory formation. Copyright © 2014 John Wiley & Sons, Ltd.
Seed dispersal by rhesus macaques Macaca mulatta in Northern India
Authors: Sengupta Asmita , McConkey Kim R. , Radhakrishna Sindhu
Published: May 2014

Frugivorous primates are important seed dispersers and their absence from forest patches is predicted to be detrimental to tropical forest regeneration and recruitment. With the reduction of primate populations globally, ecologically resilient primate species, characterized by dietary flexibility and the ability to thrive in a variety of habitats, assume new importance as seed dispersers. The most widely distributed non‐human primate, the rhesus macaque Macaca mulatta has been intensively studied but little is known about its role in maintaining ecosystem structure and functions. Due to their frugivorous diet, large group sizes, large home ranges and tolerance to disturbance, rhesus macaques may be effective seed dispersers. We studied seed dispersal by rhesus macaques at the Buxa Tiger Reserve, India, through a combination of behavioural observations and germination experiments. Rhesus macaques dispersed 84% of the 49 species they fed on either through spitting or defecation. Nearly 96% of the handled seeds were undamaged and 61% of the species for which germination tests were performed had enhanced germination. Almost 50% of the monitored seeds among those deposited in situ germinated and 22% established seedlings, suggesting that rhesus macaques are important seed dispersers in tropical forests. Due to their widespread distribution and large populations, rhesus macaques are perceived as common and are categorized as Least Concern on the IUCN Red List, effectively excluding them from any conservation plans. Based on the results of our study, we argue that rhesus macaques fulfill critical ecological functions in their habitat and that this parameter must be taken into consideration when they are reviewed for conservation priorities. Am. J. Primatol. 76:1175–1184, 2014. © 2014 Wiley Periodicals, Inc.
Thermoplastic composites of polyamide‐12 reinforced by cellulose nanofibers with cationic surface modification
Authors: Semba Takeshi , Ito Akihiro , Kitagawa Kazuo , Nakatani Takeshi , Yano Hiroyuki , Sato Akihiro
Published: May 2014

Cellulose nanofibers (CNFs) have many useful properties, including high strength and low thermal expansion, and are also environmentally friendly, readily renewable, safe, and biodegradable. The focus of this study was the development of lightweight thermoplastic polymer composites with good mechanical properties based on the incorporation of CNFs that have undergone surface pretreatment with a cationic reagent. The polyamide (PA12) was mixed with surface‐treated CNFs using a twin screw extruder and the resulting pellets were injection molded. The Izod impact strength without notch of CNF‐based composites exceeded that of composites incorporating organophilic montmorillonite (OMMT), a representative nanocomposite material. When the Izod impact test without notch, the impact hammer was stopped by the specimen with incorporation of surface treated CNF. Furthermore, the bending modulus and strength were equal to or greater than that of OMMT composites. The heat distortion temperature was improved as 33°C from neat PA12, and moreover improved as 29°C from OMMT composites. Cationic pretreatment of the CNF surfaces was found to increase the dispersion of the fibers and also to greatly improve the mechanical and thermal properties of the composites. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40920.
Research project tasks, data, and perceptions of data quality in a condensed matter physics community
Authors: Stvilia Besiki , Hinnant Charles C. , Wu Shuheng , Worrall Adam , Lee Dong Joon , Burnett Kathleen , Burnett Gary , Kazmer Michelle M. , Marty Paul F.
Published: May 2014

To be effective and at the same time sustainable, a community data curation model needs to be aligned with the community's current data practices, including research project activities, data types, and perceptions of data quality. Based on a survey of members of the condensed matter physics (CMP) community gathered around theNationalHighMagneticFieldLaboratory, a large national laboratory, this article defines a model ofCMPresearch project tasks consisting of 10 task constructs. In addition, the study develops a model of data quality perceptions byCMPscientists consisting of four data quality constructs. The paper also discusses relationships among the data quality perceptions, project roles, and demographic characteristics ofCMPscientists. The findings of the study can inform the design of aCMPdata curation model that is aligned and harmonized with the community's research work structure and data practices.
A complete assessment of tagging quality: A consolidated methodology
Authors: Choi Yunseon
Published: May 2014

This paper presents a methodological discussion of a study of tagging quality in subject indexing. The data analysis in the study was divided into 3 phases: analysis of indexing consistency, analysis of tagging effectiveness, and analysis of the semantic values of tags. To analyze indexing consistency, this study employed the vector space model‐based indexing consistency measures. An analysis of tagging effectiveness with tagging exhaustivity and tag specificity was conducted to ameliorate the drawbacks of consistency analysis based on only the quantitative measures of vocabulary matching. To further investigate the semantic values of tags at various levels of specificity, a latent semantic analysis (LSA) was conducted. To test statistical significance for the relation between tag specificity and semantic quality, correlation analysis was conducted. This research demonstrates the potential of tags for web document indexing with a complete assessment of tagging quality and provides a basis for further study of the strengths and limitations of tagging.
How are icons processed by the brain? Neuroimaging measures of four types of visual stimuli used in information systems
Authors: Huang Sheng‐Cheng , Bias Randolph G. , Schnyer David
Published: May 2014

We sought to understand how users interpret meanings of symbols commonly used in information systems, especially how icons are processed by the brain. We investigated Chinese and English speakers' processing of 4 types of visual stimuli: icons, pictures, Chinese characters, and English words. The goal was to examine, via functional magnetic resonance imaging (fMRI) data, the hypothesis that people cognitively process icons as logographic words and to provide neurological evidence related to human−computer interaction (HCI), which has been rare in traditional information system studies. According to the neuroimaging data of 19 participants, we conclude that icons are not cognitively processed as logographical words like Chinese characters, although they both stimulate the semantic system in the brain that is needed for language processing. Instead, more similar to images and pictures, icons are not as efficient as words in conveying meanings, and brains (people) make more effort to process icons than words. We use this study to demonstrate that it is practicable to test information system constructs such as elements of graphical user interfaces (GUIs) with neuroscience data and that, with such data, we can better understand individual or group differences related to system usage and user−computer interactions.
Framing of Decisions: Effect on Active and Passive Risk Avoidance
Authors: Huber Oswald , Huber Odilo W. , Bär Arlette S.
Published: May 2014

Decision makers intending to avoid risk in a decision situation can choose a less risky alternative (passive risk avoidance) or intervene actively in an alternative applying a risk‐defusing action (active risk avoidance). In Experiment 1 (64 participants), we compared active and passive risk defusing in two framing conditions. In the negative frame, in the uncertain alternative, a change to the worse was possible; in the positive frame, a change to an improvement was possible. Each participant decided in both framing conditions. As expected, active risk avoidance behavior for preventing a negative outcome (i.e., in the negative frame) was more likely than for promoting a positive one (i.e., in the positive frame). If decision makers did not or could not actively defuse the risk, they chose in correspondence to the classical pattern: risk avoidance in the positive frame and risk seeking in the negative one. We replicated the latter result in a second experiment (32 participants). The classical framing pattern in passive risk avoidance in both experiments is remarkable, because participants were not presented or did not search for exact probabilities. Copyright © 2014 John Wiley & Sons, Ltd.
Elevation of heat shock gene expression from static magnetic field exposure in vitro
Authors: Laramee Craig B. , Frisch Paul , McLeod Kenneth , Li Gloria C.
Published: May 2014

Previously, we found that extremely low frequency (ELF) electric fields were able to elicit an approximate 3.5‐fold increase in heat shock gene expression, a response which may have applicability to cancer therapy. Based on recent studies demonstrating the ability of magnetic fields to influence gene expression, we hypothesized that low level static magnetic fields may be able to affect heat shock gene expression while avoiding some of the clinical difficulties that arise with electric fields. Transfected rat primary cells in monolayer were exposed to magnetic fields of 1 to 440 mT for 16, 24, or 48 h starting at 24 and 48 h post transfection. Heat shock protein (HSP70) expression, as indicated by a promoter linked luciferase reporter, was followed for up to 96 h and showed a dependence on flux density, exposure duration, and start time post transfection. A nonlinear response was observed for increasing flux density with a maximum of a 3.5‐fold increase in expression for 48 h of exposure starting 48 h after transfection. These results demonstrate an enhancement of gene expression similar in magnitude to that observed with external electric field exposure, while eliminating many of the clinical complications. Bioelectromagnetics. 35:406–413, 2014. © 2014 Wiley Periodicals, Inc.
Flow‐injection chemiluminescence method to detect a β2 adrenergic agonist
Authors: Zhang Guangbin , Tang Yuhai , Shang Jian , Wang Zhongcheng , Yu Hua , Du Wei , Fu Qiang
Published: May 2014

A new method for the detection of β2 adrenergic agonists was developed based on the chemiluminescence (CL) reaction of β2 adrenergic agonist with potassium ferricyanide–luminol CL. The effect of β2 adrenergic agonists including isoprenaline hydrochloride, salbutamol sulfate, terbutaline sulfate and ractopamine on the CL intensity of potassium ferricyanide–luminol was discovered. Detection of the β2 adrenergic agonist was carried out in a flow system. Using uniform design experimentation, the influence factors of CL were optimized. The optimal experimental conditions were 1 mmol/L of potassium ferricyanide, 10 µmol/L of luminol, 1.2 mmol/L of sodium hydroxide, a flow speed of 2.6 mL/min and a distance of 1.2 cm from ‘Y2’ to the flow cell. The linear ranges and limit of detection were 10–100 and 5 ng/mL for isoprenaline hydrochloride, 20–100 and 5 ng/mL for salbutamol sulfate, 8–200 and 1 ng/mL for terbutaline sulfate, 20–100 and 4 ng/mL for ractopamine, respectively. The proposed method allowed 200 injections/h with excellent repeatability and precision. It was successfully applied to the determination of three β2 adrenergic agonists in commercial pharmaceutical formulations with recoveries in the range of 96.8–98.5%. The possible CL reaction mechanism of potassium ferricyanide–luminol–β2 adrenergic agonist was discussed from the UV/vis spectra. Copyright © 2014 John Wiley & Sons, Ltd.
Simultaneous inhibition of key growth pathways in melanoma cells and tumor regression by a designed bidentate constrained helical peptide
Authors: Dhar Amlanjyoti , Mallick Shampa , Ghosh Piya , Maiti Atanu , Ahmed Israr , Bhattacharya Seemana , Mandal Tapashi , Manna Asit , Roy Koushik , Singh Sandeep , Nayak Dipak Kumar , Wilder Paul T. , Markowitz Joseph , Weber David , Ghosh Mrinal K. , Chattopadhyay Samit , Guha Rajdeep , Konar Aditya , Bandyopadhyay Santu , Roy Siddhartha
Published: May 2014

Protein–protein interactions are part of a large number of signaling networks and potential targets for drug development. However, discovering molecules that can specifically inhibit such interactions is a major challenge. S100B, a calcium‐regulated protein, plays a crucial role in the proliferation of melanoma cells through protein–protein interactions. In this article, we report the design and development of a bidentate conformationally constrained peptide against dimeric S100B based on a natural tight‐binding peptide, TRTK‐12. The helical conformation of the peptide was constrained by the substitution of α‐amino isobutyric acid—an amino acid having high helical propensity—in positions which do not interact with S100B. A branched bidentate version of the peptide was bound to S100B tightly with a dissociation constant of 8 nM. When conjugated to a cell‐penetrating peptide, it caused growth inhibition and rapid apoptosis in melanoma cells. The molecule exerts antiproliferative action through simultaneous inhibition of key growth pathways, including reactivation of wild‐type p53 and inhibition of Akt and STAT3 phosphorylation. The apoptosis induced by the bidentate constrained helix is caused by direct migration of p53 to mitochondria. At moderate intravenous dose, the peptide completely inhibits melanoma growth in a mouse model without any significant observable toxicity. The specificity was shown by lack of ability of a double mutant peptide to cause tumor regression at the same dose level. The methodology described here for direct protein–protein interaction inhibition may be effective for rapid development of inhibitors against relatively weak protein–protein interactions for de novo drug development. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 344–358, 2014.
Constraint‐based modeling of heterologous pathways: Application and experimental demonstration for overproduction of fatty acids in Escherichia coli
Authors: Ip Kuhn , Donoghue Neil , Kim Min Kyung , Lun Desmond S.
Published: May 2014

Constraint‐based modeling has been shown, in many instances, to be useful for metabolic engineering by allowing the prediction of the metabolic phenotype resulting from genetic manipulations. But the basic premise of constraint‐based modeling—that of applying constraints to preclude certain behaviors—only makes sense for certain genetic manipulations (such as knockouts and knockdowns). In particular, when genes (such as those associated with a heterologous pathway) are introduced under artificial control, it is unclear how to predict the correct behavior. In this paper, we introduce a modeling method that we call proportional flux forcing (PFF) to model artificially induced enzymatic genes. The model modifications introduced by PFF can be transformed into a set of simple mass balance constraints, which allows computational methods for strain optimization based on flux balance analysis (FBA) to be utilized. We applied PFF to the metabolic engineering of Escherichia coli (E. coli) for free fatty acid (FFA) production—a metabolic engineering problem that has attracted significant attention because FFAs are a precursor to liquid transportation fuels such as biodiesel and biogasoline. We show that PFF used in conjunction with FBA‐based computational strain optimization methods can yield non‐obvious genetic manipulation strategies that significantly increase FFA production in E. coli. The two mutant strains constructed and successfully tested in this work had peak fatty acid (FA) yields of 0.050 g FA/g carbon source (17.4% theoretical yield) and 0.035 g FA/g carbon source (12.3% theoretical yield) when they were grown using a mixed carbon source of glucose and casamino acids in a ratio of 2‐to‐1. These yields represent increases of 5.4‐ and 3.8‐fold, respectively, over the baseline strain. Biotechnol. Bioeng. 2014;111: 2056–2066. © 2014 Wiley Periodicals, Inc.
Genetic, psychosocial, and demographic factors associated with social disinhibition in Mexican‐origin youth
Authors: Archer Natalie P. , Wilkinson Anna V. , Ranjit Nalini , Wang Jian , Zhao Hua , Swann Alan C. , Shete Sanjay
Published: May 2014

Introduction

The genetic heritability for sensation‐seeking tendencies ranges from 40 to 60%. Sensation‐seeking behaviors typically manifest during adolescence and are associated with alcohol and cigarette experimentation in adolescents. Social disinhibition is an aspect of sensation‐seeking that is closely tied to cigarette and alcohol experimentation.

Methods

We examined the contribution of candidate genes to social disinhibition among 1132 Mexican origin youth in Houston, Texas, adjusting for established demographic and psychosocial risk factors. Saliva samples were obtained at baseline in 2005–06, and social disinhibition and other psychosocial data were obtained in 2008–09. Participants were genotyped for 672 functional and tagging SNPs potentially related to sensation‐seeking, risk‐taking, smoking, and alcohol use.

Results

Six SNPs were significantly associated with social disinhibition scores, after controlling for false discovery and adjusting for population stratification and relevant demographic/psychosocial characteristics. Minor alleles for three of the SNPs (rs1998220 on OPRM1; rs9534511 on HTR2A; and rs4938056 on HTR3B) were associated with increased risk of social disinhibition, while minor alleles for the other three SNPs (rs1003921 on KCNC1; rs16116 downstream of NPY; and rs16870286 on LINC00518) exhibited a protective effect. Age, linguistic acculturation, thrill and adventure‐seeking, and drug and alcohol‐seeking were all significantly positively associated with increased risk of social disinhibition in a multivariable model (P < 0.001).

Conclusions

These results add to our knowledge of genetic risk factors for social disinhibition. Additional research is needed to verify whether these SNPs are associated with social disinhibition among youth of different ethnicities and nationalities, and to elucidate whether and how these SNPs functionally contribute to social disinhibition.
Hierarchical mesh deformation with shape preservation
Authors: Zhao Yong , Dong Junyu , Pan Bin , Xiao Chunxia
Published: May 2014

It is very difficult to deform flexible objects in computer animation. This paper presents a novel approach to address this problem. A detail‐sensitive and deformation‐sensitive simplification is first conducted on the original mesh. The simplified mesh is then deformed, and this deformation is transferred to the original mesh to produce an initial result. Because of the discontinuity between some vertices, an as‐rigid‐as‐possible optimization is employed to prevent the shape distortion and control the surface stiffness. Various experimental data demonstrate that our algorithm is intuitive, efficient, and effective in deforming large meshes. Copyright © 2014 John Wiley & Sons, Ltd.
Decompositions using maximum signal factors
Authors: Gallagher Neal B. , Shaver Jeremy M. , Bishop Randall , Roginski Robert T. , Wise Barry M.
Published: May 2014

Maximum autocorrelation factors (MAF) and whitened principal components analysis are gaining popularity as tools for exploratory analysis of hyperspectral images. This paper shows that the two approaches are mathematically identical when signal and noise (clutter) are defined similarly. It also shows that the MAF metaphor can be generalized to encompass a wide variety of signal processing objectives referred to generically as maximum signal factors while retaining the interpretability of principal components analysis. A subspace projection approximation of the data prior to decomposition is also introduced, which reduces computational memory requirements. For the hyperspectral images studied, it was demonstrated to bring more signal of interest into the first factor as compared with the approach that did not use the subspace approximation. Also, it is expected to significantly reduce the number of scores images needed to be inspected during exploratory analysis. Copyright © 2014 John Wiley & Sons, Ltd.
Diet and proinflammatory cytokine levels in head and neck squamous cell carcinoma
Authors: Arthur Anna E. , Peterson Karen E. , Shen Jincheng , Djuric Zora , Taylor Jeremy M. G. , Hebert James R. , Duffy Sonia A. , Peterson Lisa A. , Bellile Emily L. , Whitfield Joel R. , Chepeha Douglas B. , Schipper Matthew J. , Wolf Gregory T. , Rozek Laura S.
Published: May 2014

BACKGROUND

Proinflammatory cytokine levels may be associated with cancer stage, recurrence, and survival. The objective of this study was to determine whether cytokine levels were associated with dietary patterns and fat‐soluble micronutrients in patients with previously untreated head and neck squamous cell carcinoma (HNSCC).

METHODS

This was a cross‐sectional study of 160 patients with newly diagnosed HNSCC who completed pretreatment food frequency questionnaires (FFQs) and health surveys. Dietary patterns were derived from FFQs using principal component analysis. Pretreatment serum levels of the proinflammatory cytokines interleukin‐6 (IL‐6), tumor necrosis factor alpha (TNF‐α), and interferon gamma (IFN‐γ) were measured using an enzyme‐linked immunosorbent assay, and serum carotenoid and tocopherol levels were measured by high‐performance liquid chromatography. Multivariable ordinal logistic regression models examined associations between cytokines and quartiles of reported and serum dietary variables.

RESULTS

Three dietary patterns emerged: whole foods, Western, and convenience foods. In multivariable analyses, higher whole foods pattern scores were significantly associated with lower levels of IL‐6, TNF‐α, and IFN‐γ (P ≤ .001, P = .008, and P = .03, respectively). Significant inverse associations were reported between IL‐6, TNF‐α, and IFN‐γ levels and quartiles of total reported carotenoid intake (P = .006, P = .04, and P = .04, respectively). There was an inverse association between IFN‐γ levels and serum α‐tocopherol levels (P = .03).

CONCLUSIONS

Consuming a pretreatment diet rich in vegetables, fruit, fish, poultry, and whole grains may be associated with lower proinflammatory cytokine levels in patients with HNSCC. Cancer 2014;120:2704–2712. © 2014 American Cancer Society.
Crosstalk cancelling voltage‐mode driver for multi‐Gbps parallel DRAM interface
Authors: Kim Younghoon , Yoo Changsik
Published: May 2014

For multi‐Gb/s/pin parallel dynamic random access memory (DRAM) interface, a crosstalk cancelling voltage‐mode driver is proposed. The voltage‐mode driver is composed of a main driver and sub‐drivers where the cancellation signal is generated by the sub‐drivers. The outputs of the main driver and sub‐drivers are combined by a capacitive coupling so the direct current (DC) output swing is not affected by the crosstalk cancellation and the sub‐drivers may not consume DC power. The proposed crosstalk cancelling voltage‐mode driver implemented in a 0.11‐µm complementary metal‐oxide semiconductor (CMOS) technology improves the horizontal eye openings by 22.6 ps at 4‐Gbps/pin. Copyright © 2014 John Wiley & Sons, Ltd.
Recognizing and characterizing dynamics of cellular devices in cellular data network through massive data analysis
Authors: Liu Jun , Chang Nan , Zhang Sanguo , Lei Zhenming
Published: May 2014

The user clients for accessing Internet are increasingly shifting from desktop computers to cellular devices. To be competitive in the rapidly changing market, operators, Internet service providers and application developers are required to have the capability of recognizing the models of cellular devices and understanding the traffic dynamics of cellular data network. In this paper, we propose a novel Jaccard measurement‐based method to recognize cellular device models from network traffic data. This method is implemented as a scalable paralleled MapReduce program and achieves a high accuracy, 91.5%, in the evaluation with 2.9 billion traffic records collected from the real network. Based on the recognition results, we conduct a comprehensive study of three characteristics of network traffic from device model perspective, the network access time, the traffic volume, and the diurnal patterns. The analysis results show that the distribution of network access time can be modeled by a two‐component Gaussian mixture model, and the distribution of traffic volumes is highly skewed and follows the power law. In addition, seven distinct diurnal patterns of cellular device usage are identified by applying unsupervised clustering algorithm on the collected massive traffic data. Copyright © 2014 John Wiley & Sons, Ltd.
Isotope Effect of Thermopower in the TTFCOONH3Ph Single Crystal
Authors: Kobayashi Yuka , Sumi Satoshi , Terauchi Takeshi , Iwai Hideo , Tanaka Akihiro , Matsushita Yoshitaka , Sato Akira
Published: May 2014

The thermopowers of single‐crystalline anilinium tetrathiafulvalene‐2‐carboxylate (TTFCOONH3Ph) and its deuteriated form (TTFCOOND3Ph) have been examined at room temperature, and a significant isotope effect was found: 102 μV/K for TTFCOONH3Ph, and 48 μV/K for TTFCOOND3Ph, which amounts to a difference of a factor of around two. The origin of the difference, for example, X‐ray crystal structure and doping level, was examined based on chemical and physical characterizations, and it was found that very low ion transport drastically enhances the thermopower of holes, giving rise to the large isotope effect.
Bioaccumulation of organochlorine contaminants and ethoxyresorufin-o-deethylase activity in southern California round stingrays (Urobatis halleri) exposed to planar aromatic compounds
Authors: Lyons Kady , Lavado Ramon , Schlenk Daniel , Lowe Christopher G.
Published: May 2014

While contaminant concentrations have been reported for elasmobranchs around the world, no studies have examined bioaccumulation patterns across male and female age classes. The round stingray (Urobatis halleri) is a local benthic species that forages near areas of high organochlorine contamination and represents a good elasmobranch model. Polychlorinated biphenyls (PCBs), DDT, and chlordanes were measured in juvenile and adult male and female stingrays from areas in southern California, USA (n = 208), and a nearby offshore island, Santa Catalina (n = 34). Both mainland juvenile male and female stingrays showed a significant dilution effect. After maturity, summed contaminant concentrations significantly increased with size for adult males (median 11.1 µg/g lipid wt) and females (5.2 µg/g lipid wt). However, the rate of bioaccumulation was substantially greater in male stingrays than in females, likely a result of the females' ability to offload contaminants to offspring during pregnancy. In addition, males and females showed significant differences in their contaminant profiles, suggesting differential habitat use. Male and female stingrays collected from Santa Catalina Island had significantly lower concentrations (0.51 µg/g and 0.66 µg/g lipid wt, respectively), approximately 5 times less than those of mainland animals. Potential toxicity effects mediated through activation of the aryl hydrocarbon receptor were explored through ethoxyresorufin-O-deethylase (EROD) activity assays. Mainland male stingrays exhibited significantly greater EROD activities than Catalina males (481 pmol/min/mg protein and 55 pmol/min/mg protein, respectively); however, activity levels in female stingrays from both locations were comparable (297 pmol/min/mg protein and 234 pmol/min/mg protein, respectively) and lower than those in mainland males. The results suggest that PCBs and/or other structurally related contaminants may be inducing a biological response in mainland males but not females, possibly the result of a dampening effect of estradiol; however, the exact physiological repercussions of exposure remain to be determined. Environ Toxicol Chem 2014;33:1380–1390. © 2014 SETAC
Synthesis of small libraries of natural products: New esters of long‐chain alcohols from the essential oil of Scandix pecten‐veneris L. (Apiaceae)
Authors: Radulović Niko S. , Mladenović Marko Z. , Stojanović‐Radić Zorica Z.
Published: May 2014

Scandix pecten‐veneris L. (Apiaceae) is a weed species used in Iran and Turkey for medicinal purposes. The latest phytochemical reports on this umbellifer date to the 1980s. Motivated by a recent discovery of a series of chemotaxonomically important volatile long‐chain n‐alkyl isomeric butanoates and pentanoates from a related taxon, S. balansae, the aim of this work was to reinvestigate the chemical composition of the essential oil of S. pecten‐veneris. Gas chromatography (GC) and GC combined with mass spectrometry (MS) analyses of the root, aerial part and fruit essential oils revealed the presence of 14 isomeric butanoates and pentanoates of long‐chain 1‐alkanols (C13–C18, C21 and C23). A small synthetic library of the tentatively identified esters allowed the final identity corroboration and screening of their antimicrobial activity. Among 123 successfully identified compounds in seven samples, seven esters (n‐C15, C17, C21 and C23 isobutyrates, as well as n‐C13, C15 and C17 isovalerates) turned out to be new natural metabolites and these were fully spectrally characterized (nuclear magnetic resonance, infrared, MS). All detected esters were quantified by GC with flame ionization detector (FID) calibration curves: 0.02–3.27 mg of these esters per 100 g of dry roots, aerial parts or fruits. The availability of the synthetic library made it possible to examine structure–antimicrobial activity relationships. The reinvestigation of S. pecten‐veneris essential oil by standard analytical methods and the application of the synthetic approach presented the possibility of identifying very rare minor plant metabolites previously unidentifiable and provided relevant data for dereplication of other related secondary metabolites. Copyright © 2014 John Wiley & Sons, Ltd.
Attribution of emotions to body postures: An independent component analysis study of functional connectivity in autism
Authors: Libero Lauren E. , Stevens Carl E. , Kana Rajesh K.
Published: May 2014

The ability to interpret others' body language is a vital skill that helps us infer their thoughts and emotions. However, individuals with autism spectrum disorder (ASD) have been found to have difficulty in understanding the meaning of people's body language, perhaps leading to an overarching deficit in processing emotions. The current fMRI study investigates the functional connectivity underlying emotion and action judgment in the context of processing body language in high‐functioning adolescents and young adults with autism, using an independent components analysis (ICA) of the fMRI time series. While there were no reliable group differences in brain activity, the ICA revealed significant involvement of occipital and parietal regions in processing body actions; and inferior frontal gyrus, superior medial prefrontal cortex, and occipital cortex in body expressions of emotions. In a between‐group analysis, participants with autism, relative to typical controls, demonstrated significantly reduced temporal coherence in left ventral premotor cortex and right superior parietal lobule while processing emotions. Participants with ASD, on the other hand, showed increased temporal coherence in left fusiform gyrus while inferring emotions from body postures. Finally, a positive predictive relationship was found between empathizing ability and the brain areas underlying emotion processing in ASD participants. These results underscore the differential role of frontal and parietal brain regions in processing emotional body language in autism. Hum Brain Mapp 35:5204–5218, 2014. © 2014 Wiley Periodicals, Inc.
The dual facet of gamma oscillations: Separate visual and decision making circuits as revealed by simultaneous EEG/fMRI
Authors: Castelhano João , Duarte Isabel Catarina , Wibral Michael , Rodriguez Eugénio , Castelo‐Branco Miguel
Published: May 2014

It remains an outstanding question whether gamma‐band oscillations reflect unitary cognitive processes within the same task. EEG/MEG studies do lack the resolution or coverage to address the highly debated question whether single gamma activity patterns are linked with multiple cognitive modules or alternatively each pattern associates with a specific cognitive module, within the same coherent perceptual task. One way to disentangle these issues would be to provide direct identification of their sources, by combining different techniques. Here, we directly examined these questions by performing simultaneous EEG/fMRI using an ambiguous perception paradigm requiring holistic integration. We found that distinct gamma frequency sub‐bands reflect different neural substrates and cognitive mechanisms when comparing object perception states vs. no categorical perception. A low gamma sub‐band (near 40 Hz) activity was tightly related to the decision making network, and in particular the anterior insula. A high gamma sub‐band (∼60 Hz) could be linked to early visual processing regions. The demonstration of a clear functional topography for distinct gamma sub‐bands within the same task shows that distinct gamma‐band modulations underlie sensory processing and perceptual decision mechanisms. Hum Brain Mapp 35:5219–5235, 2014. 2014 Wiley Periodicals, Inc.
Oncologic outcomes of supratracheal laryngectomy: Critical analysis
Authors: Rizzotto Giuseppe , Crosetti Erika , Lucioni Marco , Bertolin Andy , Monticone Valentina , Sprio Andrea Elio , Berta Giovanni Nicolao , Succo Giovanni
Published: May 2014

Background

Laryngeal cancer management should pursue function‐sparing therapeutic options. Even though demolitive surgery provides better control of disease at intermediate to advanced stages when compared to chemoradiotherapy, it does not preserve laryngeal function. Supratracheal partial laryngectomy has been described as a function‐sparing surgical technique for laryngeal cancer with subglottic extension.

Methods

In this retrospective study, we analyzed the clinical outcomes of 115 patients who underwent supratracheal partial laryngectomy.

Results

At 5 years, overall survival (OS), disease‐free survival (DFS), and locoregional control rates were 78.9%, 68.5%, and 69.6%, respectively; DFS and locoregional control prevalences were greatly affected by pT4a classification (49.0% and 51.4%, respectively); and laryngeal function preservation was maintained in 78.3% of patients despite being affected by pT4a classification (59.3%) and age ≥65 (64.6%).

Conclusion

For cases with glottic tumors and with subglottic extension, the choice of supratracheal partial laryngectomy versus chemoradiotherapy can be considered to be effective in terms of prognostic and functional results. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1417–1424, 2015
Unique recurrence patterns of cervical intraepithelial neoplasia after excision of the squamocolumnar junction
Authors: Herfs Michael , Somja Joan , Howitt Brooke E. , Suarez‐Carmona Meggy , Kustermans Gaelle , Hubert Pascale , Doyen Jean , Goffin Frederic , Kridelka Frederic , Crum Christopher P. , Delvenne Philippe
Published: May 2014

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamocolumnar junction (SCJ) and suggest that these cells may not regenerate after excision (loop electrosurgical excision procedure). Our study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (human papillomavirus, HPV) characteristics of recurrent CIN. One hundred and thirty‐one consecutive patients treated by excision and attending follow‐up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype and SCJ immunophenotype. During the follow‐up period (up to 4 years), 16 (12.2%) recurrences were identified. Four (25%) were identified at the first follow‐up visit, closely resembled the initial CIN 2/3 in grade and HPV type and were typically SCJ marker positive [SCJ(+)], suggesting nonexcised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (−). In total, 9 out of 11 SCJ (−) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This markedly lower risk of CIN 2/3 after successful SCJ excision suggests that the removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer.
IGFBP-2 Directly Stimulates Osteoblast Differentiation
Authors: Xi Gang , Wai Christine , DeMambro Victoria , Rosen Clifford J , Clemmons David R
Published: May 2014

Insulin-like growth factor binding protein 2 (IGFBP-2) is important for acquisition of normal bone mass in mice; however, the mechanism by which IGFBP-2 functions is not defined. These studies investigated the role of IGFBP-2 in stimulating osteoblast differentiation. MC-3T3 preosteoblasts expressed IGFBP-2, and IGFBP-2 knockdown resulted in a substantial delay in osteoblast differentiation, reduced osteocalcin expression and Alizarin red staining. These findings were replicated in primary calvarial osteoblasts obtained from IGFBP-2−/− mice, and addition of IGFBP-2 rescued the differentiation program. In contrast, overexpression of IGFBP-2 accelerated the time course of differentiation as well as increasing the total number of differentiating cells. By day 6, IGFBP-2–overexpressing cells expressed twice as much osteocalcin as control cultures and this difference persisted. To determine the mechanism by which IGFBP-2 functions, the interaction between IGFBP-2 and receptor tyrosine phosphatase β (RPTPβ) was examined. Disruption of this interaction inhibited the ability of IGFBP-2 to stimulate AKT activation and osteoblast differentiation. Knockdown of RPTPβ enhanced osteoblast differentiation, whereas overexpression of RPTPβ was inhibitory. Adding back IGFBP-2 to RPTPβ-overexpressing cells was able to rescue cell differentiation via enhancement of AKT activation. To determine the region of IGFBP-2 that mediated this effect, an IGFBP-2 mutant that contained substitutions of key amino acids in the heparin-binding domain-1 (HBD-1) was prepared. This mutant had a major reduction in its ability to stimulate differentiation of calvarial osteoblasts from IGFBP-2−/− mice. Addition of a synthetic peptide that contained the HBD-1 sequence to calvarial osteoblasts from IGFBP-2−/− mice rescued differentiation and osteocalcin expression. In summary, the results clearly demonstrate that IGFBP-2 stimulates osteoblast differentiation and that this effect is mediated through its heparin-binding domain-1 interacting with RPTPβ. The results suggest that stimulation of differentiation is an important mechanism by which IGFBP-2 regulates the acquisition of normal bone mass in mice. © 2014 American Society for Bone and Mineral Research.