bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Characterization of Folate‐decorated Cobalt Ferrite Nanoparticles Coated with Poly(Ethylene Glycol) for Biomedical Applications
Authors: Nasiri Mahtab , Hassanzadeh‐Tabrizi Sayed Ali
Published: November 2017

A stable and biocompatible targeting complex CFNs@PEG‐FA is developed. The initially synthesized cobalt ferrite nanoparticles (CFNs) were treated with poly(ethylene glycol) (PEG) in order to improve biocompatibility of the CFNs. Citric acid (CA) was used as the coupling agent, which made PEG to bond with the CFNs. CFNs@PEG were conjugated with folic acid (FA) to synthesize CFNs@PEG‐FA, which was capable of targeting the FA receptor positive (FAR+) cancer cells. Synthesized nanoparticles were physically and chemically analyzed using EDX, FT‐IR, XRD, TGA, FESEM, TEM, DLS, and VSM. The biocompatibility of CFNs@PEG‐FA was assessed in vitro on HSF 1184 (human skin fibroblast cells) and HeLa (human cervical cancer cell, FAR+) using MTT assay and AO/EB staining florescence method. High level of CFNs@PEG‐FA binding to HeLa was confirmed through quantitative and qualitative in vitro targeting studies. Results show that CFNs@PEG‐FA can be a potential biomaterial for use in biomedical trials, especially magnetic hyperthermia. The findings through this in vitro study are to be compared in future with those of in vivo studies.
Prognostic predictability of the new American Joint Committee on Cancer 8th staging system for distal bile duct cancer: limited usefulness compared with the 7th staging system
Authors: Kang Jae Seung , Lee Seungyeoun , Son Donghee , Han Youngmin , Lee Kyung Bun , Kim Jae Ri , Kwon Wooil , Kim Sun‐Whe , Jang Jin‐Young
Published: November 2017

Background

The new 8th American Joint Committee on Cancer (AJCC) staging has recently been released and there are major changes in distal bile duct (DBD) cancer staging. However, clinical validation is needed before the changes can be widely implemented.

Methods

This study was performed to evaluate the prognostic predictability of the 8th AJCC staging compared with that of the 7th using C statistics.

Results

A total of 293 consecutive patients who had curative‐intended surgery were enrolled. There was no significant difference of the 5‐year survival rate between 7th T1 and T2 (P = 0.123), but significant difference between T2 and T3 (P = 0.039). There were significant differences in pairwise comparisons between the 8th T stage (T1 vs. T2, P = 0.001; T2 vs. T3, P = 0.014). The number of regional lymph node metastases also showed prognostic predictability. The 8th T and N stage both showed comparable prognostic predictability with the 7th (95% confidential intervals for C; T, −0.043 −0.097, N, −0.001 – 0.008).

Conclusions

The 8th AJCC staging for DBD cancer does not have better prognostic predictability than the 7th stage does. The previous pathologic results would become useless unless they were reviewed entirely. Therefore, introduction of the AJCC 8th staging has to be reconsidered, especially for new T staging.
The structure of the cutaneous pedal glands in the banded snail Cepaea hortensis (Müller, 1774)
Authors: von Byern Janek , Cyran Norbert , Klepal Waltraud , Rudoll Livia , Suppan Johannes , Greistorfer Sophie
Published: November 2017

Although gastropods have been crawling through the ocean and on the land for 60 million years, we still know very little about the sticky mucus produced in their foot. Most research has been focused on marine species in particular and, to a lesser extent, on the well‐known terrestrial species Arion vulgaris and Cornu aspersum. Within this study, we aim to characterize the foot anatomy of a smaller representative of the family Helicidae, the banded snail Cepaea hortensis. We are particularly interested in the microanatomy of the foot glands, their position, and the histochemical nature of their secretory content. Characterization of the dorsal foot region of Cepaea hortensis reveals four glands, differing in their size and in the granules produced. Histochemically, three of them react positively for sugars (PAS staining and lectin affinity tests for mannose, glucose and N‐acetyl‐d‐glucosamine) and acidic proteins (positive Alcian blue and Toluidine blue staining), indicating the presence of acidic glycosaminoglycans. The fourth gland type does not react to any of these dyes. The ventral pedal region includes two different gland types, which are positive for the presence of acidic glycoproteins, with a lectin affinity for mannose only. A comparison with Helix pomatia indicates differences regarding the number of glands and their contents. In Helix, only three gland types are described in the dorsal region of the foot, which show a similar granular appearance but nevertheless differ in their chemical composition. Congruently, there are two gland types in the ventral region in both species, whereas in Helix an additional sugar moiety is found. This raises the question whether these differences between the pedal glandular systems of both helicid species are the result of protection or size‐related adaptations, as they occur in the same habitat.
Screening and identification of potential hypoglycemic components in Zeng Ye Tang by high‐performance liquid chromatography coupled with tandem quadrupole time‐of‐flight mass spectrometry
Authors: Tian Yu Shan , Du Zhong Ying , Xiao Ying , Yu BoYang , Qi Jin
Published: November 2017

Zeng Ye Tang, a famous prescription consisting of Xuanshen, Maidong, and Shengdi (5:4:4), has been used in China for a long time to treat diabetes caused by excessive heat with yin deficiency. Although many studies have investigated the pharmacological effects of Zeng Ye Tang, the compounds responsible for its hypoglycemic effect have not been identified. In this study, 50 compounds in Zeng Ye Tang were identified by high‐performance liquid chromatography coupled with tandem quadrupole time‐of‐flight mass spectrometry. From these 50 compounds, nine cell‐interacted compounds were identified by biospecific cell extraction using 3T3‐L1 adipocytes. Moreover, nine potential active compounds that could be released into the blood were also acquired through serum pharmacochemical analysis in normal and diabetic rats after administration with Zeng Ye Tang. According to the established quantitative analytical method of nine constituents by high‐performance liquid chromatography, six shared prototype constituents (catalpol/harpagide/p‐coumaric acid/harpagoside/angoroside C/cinnamic acid (75.56:19.74:1.00:15.11:20.36:7.65), were screened and verified to exert remarkable hypoglycemic activity on type 2 diabetic mice. In conclusion, the six shared constituents may be responsible for the hypoglycemic activity of Zeng Ye Tang.
Spectral gaps for the Dirichlet‐Laplacian in a 3‐D waveguide periodically perturbed by a family of concentrated masses
Authors: Bakharev Fedor L. , Pérez M. Eugenia
Published: November 2017

We consider a spectral problem for the Laplace operator in a periodic waveguide perturbed by a family of “heavy concentrated masses”; namely, Π contains small regions of high density, which are periodically distributed along the z axis. Each domain has a diameter and the density takes the value in and 1 outside; m and ε are positive parameters, , . Considering a Dirichlet boundary condition, we study the band‐gap structure of the essential spectrum of the corresponding operator as . We provide information on the width of the first bands and find asymptotic formulas for the localization of the possible gaps.
Well‐posedness and exponential decay for laminated Timoshenko beams with time delays and boundary feedbacks
Authors: Feng Baowei
Published: November 2017

This paper is concerned with laminated beams modeled from the well‐established Timoshenko system with time delays and boundary feedbacks. By using semigroup method, we prove the global well‐posedness of solutions. Assuming the weights of the delay are small, we establish the exponential decay of energy to the system by using an appropriate Lyapunov functional.
Gut Microbiota Interacts with Markers of Adipose Tissue Browning, Insulin Action and Plasma Acetate in Morbid Obesity
Authors: Moreno‐Navarrete José María , Serino Matteo , Blasco‐Baque Vincent , Azalbert Vincent , Barton Richard H. , Cardellini Marina , Latorre Jèssica , Ortega Francisco , Sabater‐Masdeu Mònica , Burcelin Rémy , Dumas Marc‐Emmanuel , Ricart Wifredo , Federici Massimo , Fernández‐Real José Manuel
Published: November 2017

Scope

To examine the potential relationship among gene expression markers of adipose tissue browning, gut microbiota, and insulin sensitivity in humans.

Methods and results

Gut microbiota composition and gene markers of browning are analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue from morbidly obese subjects (n = 34). Plasma acetate is measured through 1H NMR and insulin sensitivity using euglycemic hyperinsulinemic clamp. Subjects with insulin resistance show an increase in the relative abundance (RA) of the phyla Bacteroidetes and Proteobacteria while RA of Firmicutes is decreased. In all subjects, Firmicutes RA is negatively correlated with HbA1c and fasting triglycerides, whereas Proteobacteria RA was negatively correlated with insulin sensitivity. Firmicutes RA is positively associated with markers of brown adipocytes (PRDM16, UCP1, and DIO2) in SAT, but not in VAT. Multivariate regression analysis indicates that Firmicutes RA contributes significantly to SAT PRDM16, UCP1, and DIO2 mRNA variance after controlling for age, BMI, HbA1c, or insulin sensitivity. Interestingly, Firmicutes RA, specifically those bacteria belonging to the Ruminococcaceae family, is positively associated with plasma acetate levels, which are also linked to SAT PRDM16 mRNA and insulin sensitivity.

Conclusion

Gut microbiota composition is linked to adipose tissue browning and insulin action in morbidly obese subjects, possibly through circulating acetate.
Non‐motor manifestations in ALS patients with tracheostomy and invasive ventilation
Authors: Nakayama Yuki , Shimizu Toshio , Matsuda Chiharu , Haraguchi Michiko , Hayashi Kentaro , Mochizuki Yoko , Nagao Masahiro , Kawata Akihiro , Isozaki Eiji
Published: November 2017

Introduction

This study aimed to investigate non‐motor manifestations in amyotrophic lateral sclerosis (ALS) patients with tracheostomy and invasive ventilation (TIV) and their relevance to disease progression.

Methods

Sixty‐seven ALS patients with TIV were enrolled, and followed‐up prospectively. The patients were classified at the final evaluation into two subgroups according to the duration of TIV use or disease stage measured by communication impairment. We identified non‐motor manifestations and investigated their frequencies and differences across the stages.

Results

The non‐motor manifestations were macroglossia (22.4%), unstable blood pressure (38.8%), hypothermia (26.9%), dysuria (50.7%), and hyperglycemia (12.1%). These manifestations occurred significantly more frequently in patients with TIV ≥5 years than in patients with TIV <5 years, and more in patients with severe communication impairment than in those with preserved communication ability.

Discussion

Non‐motor manifestations are observed at a high rate in ALS patients with TIV, and are possibly related to disease progression. Muscle Nerve 57: 735–741, 2018
Influence of seismic motions on behavior of piles in liquefied soils
Authors: Chatterjee Kaustav , Choudhury Deepankar
Published: November 2017

In the present study an analytical procedure based on finite element technique is proposed to investigate the influence of vertical load on deflection and bending moment of a laterally loaded pile embedded in liquefiable soil, subjected to permanent ground displacement. The degradation of subgrade modulus due to soil liquefaction and effect of nonlinearity are also considered. A free headed vertical concrete elastic nonyielding pile with a floating tip subjected to vertical compressive loading, lateral load, and permanent ground displacement due to earthquake motions, in liquefiable soil underlain by nonliquefiable stratum, is considered. The input seismic motions, having varying range of ground motion parameters, considered here include 1989 Loma Gilroy, 1995 Kobe, 2001 Bhuj, and 2011 Sikkim motions. It is calculated that maximum bending moment occurred at the interface of liquefiable and nonliquefiable soil layers and when thickness of liquefiable soil layer is around 60% of total pile length. Maximum bending moment of 1210 kNm and pile head deflection of 110 cm is observed because of 1995 Kobe motion, while 2001 Bhuj and 2011 Sikkim motions amplify the pile head deflection by 14.2 and 14.4 times and bending moment approximately by 4 times, when compared to nonliquefiable soil. Further, the presence of inertial load at the pile head increases bending moment and deflection by approximately 52% when subjected to 1995 Kobe motion. Thus, it is necessary to have a proper assessment of both kinematic and inertial interactions due to free field seismic motions and vertical loads for evaluating pile response in liquefiable soil.
Differentiating the histologic grades of gliomas preoperatively using amide proton transfer‐weighted (APTW) and intravoxel incoherent motion MRI
Authors: Zou Tianyu , Yu Hao , Jiang Chunxiu , Wang Xianlong , Jiang Shanshan , Rui Qihong , Mei Yingjie , Zhou Jinyuan , Wen Zhibo
Published: November 2017

The purpose of this work was to investigate the diagnostic performance of amide proton transfer‐weighted (APTW) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the preoperative grading of gliomas. Fifty‐one patients with suspected gliomas were recruited and underwent a preoperative MRI examination that included APTW and IVIM sequences. All cases were confirmed by postsurgical histopathology. APTW signal intensity, true diffusion coefficient (D), perfusion fraction (f) and pseudo‐diffusion coefficient (D*) were applied to assess the solid tumor component and contralateral normal‐appearing white matter. The relative APTW signal intensity (rAPTW) was also used. Independent‐sample and paired‐sample t‐tests were used to compare differences in MRI parameters between low‐grade glioma (LGG) and high‐grade glioma (HGG) groups. The diagnostic performance was assessed with the receiver operating characteristic curve. Twenty‐six patients were pathologically diagnosed with LGG and 25 were diagnosed with HGG. APTW, rAPTW and f values were significantly higher (all p < 0.001), whereas D values were significantly lower (p < 0.001) in the HGG group than in the LGG group. There was no significant difference between D* values for the two groups. rAPTW had an area under the curve (AUC) of 0.957, with a sensitivity of 100% and a specificity of 84.6%, followed by APTW, f, D and D*. The combined use of APTW and IVIM showed the best diagnostic performance, with an AUC of 0.986. In conclusion, APTW and IVIM, as two promising supplementary sequences for routine MRI, could be valuable in differentiating LGGs from HGGs.
Improved resolution of glutamate, glutamine and γ‐aminobutyric acid with optimized point‐resolved spectroscopy sequence timings for their simultaneous quantification at 9.4 T
Authors: Dobberthien Brennen J. , Tessier Anthony G. , Yahya Atiyah
Published: November 2017

Glutamine (Gln), glutamate (Glu) and γ‐aminobutyric acid (GABA) are relevant brain metabolites that can be measured with magnetic resonance spectroscopy (MRS). This work optimizes the point‐resolved spectroscopy (PRESS) sequence echo times, TE1 and TE2, for improved simultaneous quantification of the three metabolites at 9.4 T. Quantification was based on the proton resonances of Gln, Glu and GABA at ≈2.45, ≈2.35 and ≈2.28 ppm, respectively. Glu exhibits overlap with both Gln and GABA; in addition, the Gln peak is contaminated by signal from the strongly coupled protons of N‐acetylaspartate (NAA), which resonate at about 2.49 ppm. J‐coupling evolution of the protons was characterized numerically and verified experimentally. A {TE1, TE2} combination of {106 ms, 16 ms} minimized the NAA signal in the Gln spectral region, whilst retaining Gln, Glu and GABA peaks. The efficacy of the technique was verified on phantom solutions and on rat brain in vivo. LCModel was employed to analyze the in vivo spectra. The average T2‐corrected Gln, Glu and GABA concentrations were found to be 3.39, 11.43 and 2.20 mM, respectively, assuming a total creatine concentration of 8.5 mM. LCModel Cramér–Rao lower bounds (CRLBs) for Gln, Glu and GABA were in the ranges 14–17%, 4–6% and 16–19%, respectively. The optimal TE resulted in concentrations for Gln and GABA that agreed more closely with literature concentrations compared with concentrations obtained from short‐TE spectra acquired with a {TE1, TE2} combination of {12 ms, 9 ms}. LCModel estimations were also evaluated with short‐TE PRESS and with the optimized long TE of {106 ms, 16 ms}, using phantom solutions of known metabolite concentrations. It was shown that concentrations estimated with LCModel can be inaccurate when combined with short‐TE PRESS, where there is peak overlap, even when low (<20%) CRLBs are reported.
Strength in Amalgamation: Newer Combination Agents for HIV and Implications for Practice
Authors: McCoy Christopher , Badowski Melissa , Sherman Elizabeth , Crutchley Rustin , Smith Ethan , Chastain Daniel B. ,   the Society of Infectious Diseases Pharmacists
Published: November 2017

Antiretroviral (ART) therapy for the treatment of human immunodeficiency virus (HIV) infection has undergone significant changes over the past 30 years. Many single‐tablet regimens (STRs), including newer fixed‐dose combination (FDC) tablets, are available, offering patients several options for choosing a treatment regimen that works best for them. Given these changes, patients are more likely to adhere to treatment, achieve better clinical outcomes, and experience both fewer side effects and drug‐drug interactions. Newer STRs include dolutegravir (DTG)/lamivudine (3TC)/abacavir (ABC) (Triumeq; Viiv Healthcare, Research Triangle Park, NC), rilpivirine (RPV)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (Odefsey; Gilead, Foster City, CA), RPV/FTC/tenofovir disoproxil fumarate (TDF) (Complera; Gilead), elvitegravir (EVG)/cobicistat (COBI)/FTC/TDF (Stribild; Gilead), and EVG/COBI/FTC/TAF (Genvoya; Gilead). Recently approved FDCs, such as atazanavir (ATV)/COBI (Evotaz; Bristol‐Myers Squibb, Princeton, NJ), darunavir (DRV)/COBI (Prezcobix; Janssen Products, Titusville NJ), and FTC/TAF (Descovy; Gilead), are also now available. The Department of Health and Human Services treatment guidelines for HIV recommend many of these integrase strand transfer inhibitor (INSTI) STRs as a preferred choice for initiation of treatment in both ART‐naive and ‐experienced patients because they offer comparably faster rates of virologic suppression, reduced rates of resistance development (especially with DTG), and overall better adherence than protease inhibitors or NNRTIs. Numerous phase 3 clinical trials support these recommendations including several switch or simplification clinical trials. Notably, the novel pharmacokinetic booster COBI, with its water soluble properties, has enabled the development and coformulation of a few of these STRs and FDCs. Also, a newer tenofovir salt formulation, TAF, has an advantageous pharmacokinetic profile, contributing to better overall renal and bone tolerability compared with TDF. Further simplification regimens comprising dual ART therapies are currently being explored. This review provides an overview of the clinical efficacy and safety data for these coformulated agents, highlighting the relative impact on comparative adverse events, assessing the potential for experiencing fewer drug‐drug interactions, and discussing the clinical implications regarding adherence to treatment.
Heterointerface recombination of Cu(In,Ga)(S,Se)2‐based solar cells with different buffer layers
Authors: Chantana Jakapan , Kato Takuya , Sugimoto Hiroki , Minemoto Takashi
Published: November 2017

Cu(In,Ga)(S,Se)2 solar cell is high conversion efficiency (η) thin‐film solar cell. One of the methods to further increase the η is to replace traditional CdS/ZnO buffer layers by more transparent materials to enhance carrier generation in spectral region from 330 to 550 nm. Cd0.75Zn0.25S/ZnO, thin CdS/ZnS(O,OH)/ZnO, and thin CdS/ZnS(O,OH)/Zn0.79Mg0.21O buffer layers are therefore developed to replace the traditional CdS/ZnO buffer layers in Cu(In,Ga)(S,Se)2‐based solar cells. ZnO, Zn0.79Mg0.21O, and ZnO:Al are prepared by sputtering method. Low‐surface carrier recombination, caused by low sputtering damage, is observed in the solar cells with CdS/ZnO or Cd0.75Zn0.25S/ZnO buffer layers, while the highest surface carrier recombination is presented in the solar cell with ZnS(O,OH)/ZnO buffer layer. Therefore, thin CdS/ZnS(O,OH)/ZnO or Zn0.79Mg0.21O buffer layers are applied in the solar cells to decrease surface recombination (reduced sputtering damage). Ultimately, conversion efficiencies of the solar cells with Cd0.75Zn0.25S/ZnO, thin CdS/ZnS(O,OH)/ZnO, and thin CdS/ZnS(O,OH)/Zn0.79Mg0.21O buffer layers are enhanced to 19.61, 18.60, and 18.81%, respectively, which are higher than that of 18.32% for the solar cell with the traditional CdS/ZnO buffer layers.
Progress in photovoltaic performance of organic/inorganic hybrid solar cell based on optimal resistive Si and solvent modified poly(3,4‐ethylenedioxythiophene) poly(styrenesulfonate) junction
Authors: Seo Hyunwoong , Sakamoto Daisuke , Chou Hakutatsu , Itagaki Naho , Koga Kazunori , Shiratani Masaharu
Published: November 2017

Organic/inorganic hybrid solar cells have attracted much attention with simple fabrication and high performance because the combination of organic and inorganic materials compensates their disadvantages each other. This work tried to realize highly efficient hybrid solar cell based on crystalline Si and poly(3,4‐ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) junction. Performance dependences on the resistivity of Si substrate and the thickness of PEDOT:PSS layers were analyzed. Photocurrent of hybrid solar cells strongly depended on Si substrate, while overall performance depended on total resistance of hybrid solar cells not Si substrate. The charge transfer of PEDOT:PSS layer was varied by its thickness, and the 30‐nm‐thick PEDOT:PSS layer showed the best characteristics of charge transfer. The conductivity of the PEDOT:PSS layer was finally improved by solvent treatment using acetonitrile. As a result, the photovoltaic performance was much enhanced, and it was defined by 0.56 V of VOC, 30.24 mA/cm2 of JSC, 0.68 of FF, and 11.52% of efficiency.
GLP‐1 Analogue, Exendin‐4, Modulates MAPKs Activity but not the Heat Shock Response in Human HepG2 Cells
Authors: Madhu Dhanya , Hammad Maha , Kavalakatt Sina , Khadir Abdelkrim , Tiss Ali
Published: November 2017

Purpose

Glucagon‐like peptide‐1 (GLP‐1) analogues reduce ER stress and inflammation in key metabolic organs, including the liver. However, their effects on heat shock response (HSR) and mitogen‐activated protein kinases (MAPKs) have not yet been elucidated. In the present study, we investigate whether the GLP‐1 analogue, exendin‐4, triggers the expression of HSR and increases MAPK activity under metabolic stress.

Experimental design

The effects of exendin‐4 in the presence or absence of palmitic acid (PA; 400 μm) or glucose (30 mm) in the HepG2 liver cell line are assessed using Western blots, quantitative real‐time PCR, and label‐free proteomics.

Results

Heat shock proteins (HSP60, HSP72, HSP90, and GRP78) and other chaperones are not significantly affected by exendin‐4 under the conditions tested. In contrast, the presence of exendin‐4 alone increases the MAPK phosphorylation levels (JNK, ERK1/2, and p38). For short incubation periods, in the presence of PA or glucose, treatment with exendin‐4 exhibits limited effects but significantly attenuates MAPK phosphorylation after a 24‐h incubation. Interestingly, canonical signaling pathways, such as EIF2, ILK, PKA, and Rho, are modulated by exendin‐4.

Conclusion and clinical relevance

Identifying new pathways modulated by GLP‐1 analogues will provide further insights into their benefits beyond their currently recognized roles in glycemic control, such as MAPK activity, energy homeostasis, and body weight decrease.
A Mechanism of Hot‐spots Formation at the Crack Tip of Al‐PTFE under Quasi‐static Compression
Authors: Feng Bin , Li Yu‐chun , Hao Hong , Wang Huai‐xi , Hao Yi‐fei , Fang Xiang
Published: November 2017

Generally, the Al‐PTFE (polytetrafluoroethylene) is thought to be inert under quasi‐static or static loads. However, it was found that Al‐PTFE would initiate under quasi‐static compression after a specific heat treatment procedure and the opening fracture plays a crucial role in the initiation. A unique micrographic fracture pattern which showed unstable crack propagation and a ductile‐to‐brittle transition was observed at openning cracks by SEM. Combining the observed microstructure with the stress distribution at the path of crack propagation derived from numerical simulation, a mechanism was proposed to explain the formation of “hot‐spots” at the crack tip. The temperature rise at the crack tip was estimated to be at least 612 °C, which is high enough to ignite the Al‐PTFE composite.
Structural characterization of the catalytic γ and regulatory β subunits of phosphorylase kinase in the context of the hexadecameric enzyme complex
Authors: Rimmer Mary Ashley , Nadeau Owen W. , Artigues Antonio , Carlson Gerald M.
Published: November 2017

In the tightly regulated glycogenolysis cascade, the breakdown of glycogen to glucose‐1‐phosphate, phosphorylase kinase (PhK) plays a key role in regulating the activity of glycogen phosphorylase. PhK is a 1.3 MDa hexadecamer, with four copies each of four different subunits (α, β, γ and δ), making the study of its structure challenging. Using hydrogen‐deuterium exchange, we have analyzed the regulatory β subunit and the catalytic γ subunit in the context of the intact non‐activated PhK complex to study the structure of these subunits and identify regions of surface exposure. Our data suggest that within the non‐activated complex the γ subunit assumes an activated conformation and are consistent with a previous docking model of the β subunit within the cryoelectron microscopy envelope of PhK.
Large‐scale automated function prediction of protein sequences and an experimental case study validation on PTEN transcript variants
Authors: Rifaioglu Ahmet Sureyya , Doğan Tunca , Saraç Ömer Sinan , Ersahin Tulin , Saidi Rabie , Atalay Mehmet Volkan , Martin Maria Jesus , Cetin‐Atalay Rengul
Published: November 2017

Recent advances in computing power and machine learning empower functional annotation of protein sequences and their transcript variations. Here, we present an automated prediction system UniGOPred, for GO annotations and a database of GO term predictions for proteomes of several organisms in UniProt Knowledgebase (UniProtKB). UniGOPred provides function predictions for 514 molecular function (MF), 2909 biological process (BP), and 438 cellular component (CC) GO terms for each protein sequence. UniGOPred covers nearly the whole functionality spectrum in Gene Ontology system and it can predict both generic and specific GO terms. UniGOPred was run on CAFA2 challenge target protein sequences and it is categorized within the top 10 best performing methods for the molecular function category. In addition, the performance of UniGOPred is higher compared to the baseline BLAST classifier in all categories of GO. UniGOPred predictions are compared with UniProtKB/TrEMBL database annotations as well. Furthermore, the proposed tool's ability to predict negatively associated GO terms that defines the functions that a protein does not possess, is discussed. UniGOPred annotations were also validated by case studies on PTEN protein variants experimentally and on CHD8 protein variants with literature. UniGOPred protein functional annotation system is available as an open access tool at http://cansyl.metu.edu.tr/UniGOPred.html.
Tembotrione detoxification in 4‐hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor‐resistant Palmer amaranth (Amaranthus palmeri S. Wats.)
Authors: Küpper Anita , Peter Falco , Zöllner Peter , Lorentz Lothar , Tranel Patrick J , Beffa Roland , Gaines Todd A
Published: November 2017

BACKGROUND

Resistance to the 4‐hydroxyphenylpyruvate dioxygenase (HPPD)‐inhibiting herbicide tembotrione in an Amaranthus palmeri population from Nebraska (NER) has previously been confirmed to be attributable to enhanced metabolism. The objective of this study was to identify and quantify the metabolites formed in Nebraska susceptible (NES) and resistant (NER) biotypes.

RESULTS

NER and NES formed the same metabolites. Tembotrione metabolism in NER differed from that in NES in that resistant plants showed faster 4‐hydroxylation followed by glycosylation. The T50 value (time for 50% production of the maximum 4‐hydroxylation product) was 4.9 and 11.9 h for NER and NES, respectively. This process is typically catalyzed by cytochrome P450 enzymes. Metabolism differences between NER and NES were most prominent under 28 °C conditions and herbicide application at the four‐leaf stage.

CONCLUSION

Further research with the aim of identifying the gene or genes responsible for conferring metabolic resistance to HPPD inhibitors should focus on cytochrome P450s. Such research is important because non‐target‐site‐based resistance (NTSR) poses the threat of cross resistance to other chemical classes of HPPD inhibitors, other herbicide modes of action, or even unknown herbicides. © 2017 Society of Chemical Industry
Bonding Frustration in the 9.5 GPa fcc Polymeric C60
Authors: Laranjeira Jorge , Marques Leonel , Mezouar Mohamed , Melle‐Franco Manuel , Strutyński Karol
Published: November 2017

We argue that the face‐centered cubic (fcc) polymeric C60 phase obtained at 9.5 GPa can be mapped onto the classical frustrated Ising fcc antiferromagnet. Extensive density functional theory (DFT) calculations show that at 9.5 GPa 56/65 2+2 cycloaddition polymeric bonds are formed between neighboring molecules having different standard orientations but do not form when they have the same standard orientation. These “antiferromagnetic” bonds cannot be fully satisfied in the fcc lattice of the polymeric phase, resulting in a frustrated structure. By analyzing the ground state configurations of the frustrated Ising fcc antiferromagnet, a picture of the polymeric frustrated structure was obtained.
Generating flat patterns for folded structures: Search space reduction
Authors: Vorkov Vitalii , Dewil Reginald , Cattrysse Dirk , Vandepitte Dirk , Duflou Joost R.
Published: November 2017

A significant number of packaging products can be represented as folded structures. This contribution demonstrates an approach for generating a set of feasible flat patterns based upon a graph representation of the folded structures. It presents algorithms to detect several typical design features. In order to present alternative flat patterns with different properties to the designer, it is preferred to first generate all feasible spanning trees. Two options to decrease the number of generated spanning trees are then proposed: user constraints and overlapping features. Each of these reduction possibilities is examined, and several practical examples with outcomes are shown. The presented framework shows a decrease of up to 98.5% in the number of possible flat patterns for the investigated parts.
Correlative mass spectrometry imaging, applying time‐of‐flight secondary ion mass spectrometry and atmospheric pressure matrix‐assisted laser desorption/ionization to a single tissue section
Authors: Desbenoit N. , Walch A. , Spengler B. , Brunelle A. , Römpp A.
Published: November 2017

Rationale

Mass spectrometry imaging (MSI) is a powerful tool for mapping the surface of a sample. Time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS) and atmospheric pressure matrix‐assisted laser desorption/ionization (AP‐MALDI) offer complementary capabilities. Here, we present a workflow to apply both techniques to a single tissue section and combine the resulting data for the example of human colon cancer tissue.

Methods

Following cryo‐sectioning, images were acquired using the high spatial resolution (1 μm pixel size) provided by TOF‐SIMS. The same section was then coated with a para‐nitroaniline matrix and images were acquired using AP‐MALDI coupled to an Orbitrap mass spectrometer, offering high mass resolution, high mass accuracy and tandem mass spectrometry (MS/MS) capabilities. Datasets provided by both mass spectrometers were converted into the open and vendor‐independent imzML file format and processed with the open‐source software MSiReader.

Results

The TOF‐SIMS and AP‐MALDI mass spectra show strong signals of fatty acids, cholesterol, phosphatidylcholine and sphingomyelin. We showed a high correlation between the fatty acid ions detected with TOF‐SIMS in negative ion mode and the phosphatidylcholine ions detected with AP‐MALDI in positive ion mode using a similar setting for visualization. Histological staining on the same section allowed the identification of the anatomical structures and their correlation with the ion images.

Conclusions

This multimodal approach using two MSI platforms shows an excellent complementarity for the localization and identification of lipids. The spatial resolution of both systems is at or close to cellular dimensions, and thus spatial correlation can only be obtained if the same tissue section is analyzed sequentially. Data processing based on imzML allows a real correlation of the imaging datasets provided by these two technologies and opens the way for a more complete molecular view of the anatomical structures of biological tissues.
Robust stabilization of fractional‐order plant with general interval uncertainties based on a graphical method
Authors: Zheng Shiqi , Li Wenjie
Published: November 2017

This paper concentrates on the robust stabilization of fractional‐order plant suffering from general interval uncertainties by using fractional‐order controllers. General interval uncertainties mean that the coefficients and orders of the denominator and nominator of the fractional‐order plant are all uncertain and lie in specified intervals. Two main contributions are presented, as follows. (i) Based on a graphical method, a necessary and sufficient criterion is proposed for the stabilization of the general interval fractional‐order plant. By adopting some well‐defined multivalue functions, the proposed method can explicitly construct the nonconvex boundary of the value set of the fractional system. (ii) Two alternative methods are presented to improve the computational efficiency of the stabilization test. Based on a newly developed redundancy elimination technique, the first method can avoid computing and plotting many segments, which are in the interior of the value set of the fractional system. The second method utilizes a novel convex polygon bounding approach. It can efficiently construct a convex polygon to bound the nonconvex value set of the general interval fractional system. Examples are followed to illustrate the effectiveness of the proposed methods.
Casticin impairs cell growth and induces cell apoptosis via cell cycle arrest in human oral cancer SCC‐4 cells
Authors: Chou Guan‐Ling , Peng Shu‐Fen , Liao Ching‐Lung , Ho Heng‐Chien , Lu Kung‐Wen , Lien Jin‐Cherng , Fan Ming‐Jen , La Kuang‐Chi , Chung Jing‐Gung
Published: November 2017

Casticin, a polymethoxyflavone, present in natural plants, has been shown to have biological activities including anti‐cancer activities. Herein, we investigated the anti‐oral cancer activity of casticin on SCC‐4 cells in vitro. Viable cells, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS) production, and Ca2+ production, levels of ΔΨm and caspase activity were measured by flow cytometric assay. Cell apoptosis associated protein expressions were examined by Western blotting and confocal laser microscopy. Results indicated that casticin induced cell morphological changes, DNA condensation and damage, decreased the total viable cells, induced G2/M phase arrest in SCC‐4 cells. Casticin promoted ROS and Ca2+ productions, decreases the levels of ΔΨm, promoted caspase‐3, ‐8, and ‐9 activities in SCC‐4 cells. Western blotting assay demonstrated that casticin affect protein level associated with G2/M phase arrest and apoptosis. Confocal laser microscopy also confirmed that casticin increased the translocation of AIF and cytochrome c in SCC‐4 cells. In conclusion, casticin decreased cell number through G2/M phase arrest and the induction of cell apoptosis through caspase‐ and mitochondria‐dependent pathways in SCC‐4 cells.
Estimating individual fitness in the wild using capture–recapture data
Authors: Gimenez Olivier , Gaillard Jean‐Michel
Published: November 2017

The concept of Darwinian fitness is central in evolutionary ecology, and its estimation has motivated the development of several approaches. However, measuring individual fitness remains challenging in empirical case studies in the wild. Measuring fitness requires a continuous monitoring of individuals from birth to death, which is very difficult to get in part because individuals may or may not be controlled at each reproductive event and recovered at death. Imperfect detection hampers keeping track of mortality and reproductive events over the whole lifetime of individuals. We propose a new statistical approach to estimate individual fitness while accounting for imperfect detection. Based on hidden process modelling of longitudinal data on marked animals, we show that standard metrics to quantify fitness, namely lifetime reproductive success, individual growth rate and lifetime individual contribution to population growth, can be extended to cope with imperfect detection inherent to most monitoring programs in the wild. We illustrate our approach using data collected on individual roe deer in an intensively monitored population.
A multifaceted intervention to reduce guideline non-adherence among prescribing physicians in Dutch hospitals
Authors: Bos Jacqueline M. , Natsch Stephanie , van den Bemt Patricia M. L. A. , Pot Johan L. W. , Nagtegaal J. Elsbeth , Wieringa Andre , van der Wilt Gert Jan , De Smet Peter A. G. M. , Kramers Cornelis
Published: November 2017

Background Despite the potential of clinical practice guidelines to improve patient outcomes, adherence to guidelines by prescribers is inconsistent. Objective The aim of the study was to determine whether an approach of introducing an educational programme for prescribers in the hospital combined with audit and feedback by the hospital pharmacist reduces non-adherence of prescribing physicians to key pharmacotherapeutic guidelines. Setting This prospective intervention study with a before–after design evaluated patients at surgical, urological and orthopaedic wards. Method An educational program covering pain management, antithrombotics, fluid and electrolyte management, prescribing in case of renal insufficiency, application of radiographic contrast agents and surgical antibiotic prophylaxis was presented to prescribers on the participating wards. Hospital pharmacists performed medication safety consultations, combining medication review of patients who are at risk for drug related problems with visits to ward physicians. Main outcome measure The outcome measure was the proportion of the admissions of patients in which the physician did not adhere to one or more of the included guidelines. Difference was expressed in odds ratios (OR) with 95% confidence intervals (CI). Multivariable logistic regression analysis was performed. Results 1435 Admissions of 1378 patients during the usual care period and 1195 admissions of 1090 patients during the intervention period were included. Non-adherence was observed significantly less often during the intervention period [21.8% (193/886)] as compared to the usual care period [30.5% (332/1089)]. The adjusted OR was 0.61 (95% CI 0.49–0.76). Conclusion This study shows that education and support of the prescribing physician can reduce guideline non-adherence at surgical wards.
Results of pediatric endoscopic and endoscopically assisted tympanoplasty
Authors: Isaacson Glenn , Harounian Jonathan A.
Published: November 2017

Objectives

To evaluate the success of pediatric endoscopic and endoscopically assisted transcanal cartilage inlay tympanoplasty.

Methods

Retrospective review of single surgeon experience.

Results

During a 3 year period, 30 children underwent 31 endoscopic or endoscopically assisted transcanal tympanoplasties by the senior surgeon using tragal cartilage/perichondrial inlay grafts. There were 22 boys and 8 girls, ranging in age from 3.5 to 17 years (median 6 years). All tragal cartilage grafts (31/31; 100%) survived. Twenty‐seven surgeries (27/31; 82%) resulted in an intact drum (17/31; 55%) or a microperforation (10/31; 32%). In four cases (4/31; 13%) significant perforations formed in previously unaffected portions of the drum.

Conclusion

Transcanal endoscopic cartilage inlay tympanoplasty offers a practical, minimally invasive approach to tympanoplasty for children of any age. It avoids postauricular or endaural incisions, tympanomeatal flap elevation, and canalplasty. Graft survival is uniform. Microperforation at the graft margins remained in 1/3 of children. Technical modifications may lead to higher rates of tympanic closure.
THE IDEAL DISTRIBUTION OF FARMERS: EXPLAINING THE EURO-AMERICAN SETTLEMENT OF UTAH
Authors: Yaworsky Peter M. , Codding Brian F.
Published: November 2017

Explaining how and why populations settle a new landscape is central to many questions in American archaeology. Recent advances in settlement research have adopted predictions from the Ideal Free Distribution model (IFD). While tests of IFD predictions to date rely either on archaeologically derived coarse-grained diachronic data or ethnographically derived fine-grained synchronic data, here we provide the first test using historically derived data that is both fine-grained and diachronic. Fine-grain diachronic data allow us to test model predictions at a temporal scale in line with human settlement decisions and to validate proxies for application in archaeological contexts. To test model predictions pertaining to the relationship between population density and habitat quality, we use data from the historical settlement of Utah. The results demonstrate a negative relationship between population density and the quality of habitats occupied. These results are consistent with IFD predictions, suggesting that Euro-American settlement of Utah resulted from individuals attempting to maximize individual returns via agricultural productivity. Our results provide a quantitative and testable explanation for population dispersion over time and explain the spatial distribution of population density today. The results support predictions derived from a general theory of behavior, providing an explanatory framework for colonization events worldwide.
The Bronze Age, a World of Specialists? Metalworking from the Perspective of Skill and Material Specialization
Authors: Kuijpers Maikel H. G.
Published: November 2017

This article starts from the observation that the social persona of ‘specialist’ is an important analytical unit in archaeology, typically to model social (craft) organization from a Marxist perspective. This has caused this concept to solidify around economic rather than material concerns. I argue that the ‘specialist’ has become too much an ideational concept that is no longer accurately rooted in archaeological artefacts. Hence, through a brief exploration of Early Bronze Age axes, my aim is to highlight technical skill and use this to reveal different levels of material specialization. On this basis, I suggest moving beyond the umbrella term of ‘specialist’ and using four, more precise analytical units that are better equipped to accommodate the qualitative diversity of material cultures: the amateur, showing basic knowledge but little refinement; the craftsperson, producing well-made practical objects; the master, striving for perfection and setting the norm; and the virtuoso, taking risks in creating original and unique products.
Letter From The Editor
Authors: Ferguson Heather
Published: November 2017

I joined the Review of Middle East Studies’ editorial team in a disquieting time—one in which the world we study and inhabit is engulfed by political upheavals with traumatic human, material, and environmental consequences. Although every age has its crises, it is hard not to feel that we are in a moment of critical import for the future of domestic and global relations, as nation-states once again seek to assert and extend power through increasingly xenophobic means. How grateful, then, I have been that Richard Martin's brilliant stewardship and Ashleigh Breske's managerial acumen guided RoMES into a position primed to address our role as an academic community dedicated both to the MENA region and to the global dimensions of scholarship. Rich and Ashleigh planned and steered this Issue of RoMES through the editorial process, and generously offered their time and insight while waiting for me to assume the duties of Editor and transition the office to Claremont McKenna College. We are indebted to Rich for re-mapping the vision of RoMES while presumably retired, tirelessly working through a backlog of submissions, commuting to Virginia Tech after convincing the institution to house and support the Review, and for generally embodying a spirit of dedicated service to the field we can only hope to approximate. His willingness to walk me through the intricacies of the Review process while also navigating a cross-country move further illustrates a generosity of spirit that I hope will continue to suffuse RoMES in the future. Rich and Ashleigh together also streamlined the production process, and along with the team at Cambridge University Press, I look forward to building on their efforts and maintaining RoMES as a vibrant and consistent voice in an increasingly volatile climate.
Aging and Frailty in First Nations Communities
Authors:   First Nations Information Governance Centre, Walker Jennifer D.
Published: November 2017

This study, the first published overview of aging in a nationally representative sample of First Nations seniors, used data from the First Nations Regional Health Survey Phase 2 (FNRHS 2). It is also the first application of a validated frailty index to describe aging experiences in First Nations communities. Responding to the survey were 11,043 First Nations adults. Of the 1,820 First Nations seniors who responded, 52.7 per cent (95% CI [49.4−56.1]) were not frail. The maintenance of non-frail status in First Nations adults appeared to decrease in each middle-adult age group (from 87.9% in ages 35–44 through to 63.1% in ages 55–64) and to plateau after age 65. The findings are a key step in documenting the experiences of First Nations seniors nationally from a First Nations perspective. They also highlight the key need for supportive health services and chronic disease management at younger ages.
Schaefer Receives 2017 Natural Hazards Focus Group Award for Graduate Research
Authors:   AGU
Published: November 2017

Lauren N. Schaefer will be awarded the 2017 Natural Hazards Focus Group Award for Graduate Research. She will be formally presented with the award at the 2017 American Geophysical Union Fall Meeting, to be held 11–15 December in New Orleans, La. This award recognizes “one or more promising young scientists engaged in studies of natural hazards and risks” and is given “in recognition of outstanding contributions achieved during their Ph.D. (or highest equivalent terminal degree) research.”
Karnauskas Receives 2017 Ocean Sciences Early Career Award
Authors:   AGU
Published: November 2017

Kristopher B. Karnauskas will receive the 2017 Ocean Sciences Early Career Award at the 2017 American Geophysical Union Fall Meeting, to be held 11–15 December in New Orleans, La. The award recognizes “significant contributions to and promise in the ocean sciences.”