bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of transmitted HIV‐1 drug resistance using 454 ultra‐deep‐sequencing and the DeepChek®‐HIV system
Authors: Garcia‐Diaz Ana , McCormick Adele , Booth Clare , Gonzalez Dimitri , Sayada Chalom , Haque Tanzina , Johnson Margaret , Webster Daniel
Published: November 2014

Introduction

Next‐generation sequencing (NGS) is capable of detecting resistance‐associated mutations (RAMs) present at frequencies of 1% or below. Several studies have found that baseline low‐frequency RAMs are associated with failure to first‐line HAART. One major limitation to the expansion of this technology in routine diagnostics is the complexity and laboriousness integral to bioinformatics analysis. DeepChek (ABL, TherapyEdge) is a CE‐marked software that allows automated analysis and resistance interpretation of NGS data.

Objective

To evaluate the use of 454 ultra‐deep‐sequencing (Roche® 454, Life Sciences; 454‐UDS) and DeepChek for routine baseline resistance testing in a clinical diagnostic laboratory.

Methods

107 newly diagnosed HIV‐1‐infected patients (subtypes: A, n=9; B, n=52; C, n=21; D, n=2; F, n=3; G, n=1; CRF01, n=7; CRF02, n=7; CRF06, n=1; CRF07, n=1; CRF10, n=1 and unassigned complex, n=2) with a median plasma viral load of 88,727 copies/mL (range: 1380–2,143,543) were tested by 454‐UDS and Sanger sequencing for the detection of protease and reverse transcriptase RAMs. In addition, integrase RAMs were investigated in 57 of them. Sequence analysis and resistance interpretation were performed using DeepChek applying 1% and 20% thresholds for variant detections; filters applied were comparison between Sanger and 454‐UDS, and Stanford and IAS list for resistance interpretation.

Results

The time elapsed from generation of raw 454 data (between 2,000–5,000 sequences/sample) to elaboration of a resistance report was approximately 10 minutes per sample, equivalent to the time required for the same process using Sanger sequencing. Four patients (3.7%) showed baseline resistance by Sanger and 454‐UDS at frequencies above 20%, which affected both NRTIs (n=2) and NNRTIs (n=2). In addition, 12 patients (11.2%) showed transmitted drug resistance (TDR) by 454‐UDS at frequencies below 20% affecting NRTIs (n=9), NNRTIs (n=7) and PIs (n=2). Integrase resistance was not detected at baseline by 454‐UDS or Sanger sequencing.

Conclusions

DeepChek allowed easy and rapid analysis and interpretation of NGS data, thus facilitating the incorporation of this technology in routine diagnostics. The use of NGS considerably increased the detection rates of TDR to NRTI, NNRTIs and PIs. No transmitted resistance to integrase inhibitors was found in our population by Sanger sequencing or UDS.
High frequency of antiviral drug resistance and non‐b subtypes in HIV‐1 patients failing antiviral therapy in Cuba
Authors: Kouri Vivian , Alemán Yoan , Pérez Lissette , Pérez Jorge , Fonseca Carlos , Correa Consuelo , Aragonés Carlos , Campos Jorge , Álvarez Delmis , Schrooten Yoeri , Vinken Lore , Limia Celia , Soto Yudira , Vandamme Anne‐Mieke , Van Laethem Kristel
Published: November 2014

Introduction

Emergence of HIV‐1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART) in settings with limited laboratory monitoring and drug options. The objective is to implement the surveillance of drug resistance and subtypes in HIV‐1 patients failing ART in Cuba.

Methods

This study compiled clinical and genotypic drug resistance data 588 ART‐experienced HIV‐1 patients attending a clinical center in Havana in 2009–2013. Drug resistance testing was performed as part of routine clinical care. Drug resistance mutations and levels were determined using Rega version 8.0.2.

Results

Eighty‐three percent received solely ART containing at least three drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years) and exposed to more ART regimens (median: 4 vs 2 regimens) compared to patients from 2011–2013. Nucleoside reverse transcriptase inhibitor (NRTI), non‐nucleoside RTI (NNRTI) and PI mutations were present in 83.5, 77.4 and 52.0%. Full‐class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after first‐line failure (164 patients) and in 23.1, 34.6, 3.8 and 3.1% after second‐line failure (130 patients). Subtype B (32.5%), BG recombinants (19.6%) and CRF19_cpx (16.2%) were the most prevalent genetic forms. Subtype distribution did not change significantly between 2009–2010 and 2011–2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002).

Conclusions

Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure.
Use of dolutegravir in two INI‐experienced patients with multiclass resistance resulted in excellent virological and immunological responses
Authors: Marije Hofstra Laura , Nijhuis Monique , Mudrikova Tania , Fun Axel , Schipper Pauline , Schneider Margriet , Wensing Annemarie
Published: November 2014

Introduction

Dolutegravir is a second generation integrase inhibitor with a proposed high genetic barrier to resistance. However, in clinical trials, decreased virological response was seen in a subset of patients with prior exposure to raltegravir and multiple integrase resistance mutations.

Methods

We describe two cases of HIV subtype B‐infected patients starting dolutegravir after previous failure on a raltegravir‐containing regimen with extensive resistance. Genotypic analysis was performed using population sequencing and 454 ultradeep sequencing of integrase at time of raltegravir exposure.

Results

Both patients were diagnosed in early 1990s and received mono‐ and dual therapy, followed by several cART‐regimens. Due to presence of extensive resistance, the genotypic susceptibility score of these regimens never reached a score >2 and never resulted in sustained virological suppression despite good adherence. Early 2012, the clinical condition of patient 1 worsened during persistent failure of a mega‐cART regimen despite excellent drug levels. Six major PI, six minor PI, seven NRTI, six NNRTI and two INI mutations plus DM‐virus were detected (Table 1). Ultra‐deep sequencing of integrase showed the selection of Q148R, E138K+Q148K, and N155H variants and phenotypic raltegravir resistance was demonstrated. After addition of dolutegravir and enfuvirtide to the failing regimen (zidovudine, lamivudine, tenofovir, etravirine, darunavir/ritonavir, maraviroc), viral load (VL) decreased from 244,000 to <20 cps/mL within five months, CD4‐count increased (33 to 272 mm3) and the clinical condition improved substantially. In patient 2, similar worsening of the clinical condition was observed late 2012 during persistent failure on mega‐cART. Five major PI, six minor PI, nine NRTI, seven NNRTI and one INI mutation plus DM‐virus were detected. Ultra‐deep sequencing showed selection of N155H, followed by Q95K and V151I variants and phenotypic raltegravir resistance was demonstrated. Dolutegravir was added to his failing regimen (zidovudine, lamivudine, etravirine, atazanavir/ritonavir, maraviroc) at a VL of 39,000 cps/mL. Sustained virological suppression was reached within five months with considerable increase of CD4‐count (41 to 175 mm3) and slight improvement of clinical condition.

Conclusions

We present the first patients with extensive integrase resistance who were treated with dolutegravir in clinical practice and who achieved excellent virological and immunological success. These cases demonstrate the high genetic barrier of dolutegravir.
Early clinical response and presence of viral resistant minority variants: a proof of concept study
Authors: Callegaro Annapaola , Di Filippo Elisa , Astuti Noemi , Andrea Serna Ortega Paula , Rizzi Marco , Farina Claudio , Valenti Daniela , Maggiolo Franco
Published: November 2014

Introduction

Traditional genotyping assays detect viral variants present in at least 15–25% of the entire virus population. We tested the Next generation GS Junior System (NGS) setted with a detection limit of 0.05% and evaluated the clinical relevance of low prevalent mutations.

Methods

NGS was performed on the plasma of 26 infected individuals who started a TDF/FTC/RPV (15 subjects) or TDF/FTC/EFV (11 subjects) cART after a routine HIV‐1 drug‐resistance negative test by Viroseq HIV‐1 Genotyping System. Amplicon Sequencing of HIV‐1 RT and PR Plate (Roche) was performed following the manufacturer's instructions. HIV‐1 variants were analyzed by a specific HIV‐1 tool by AVA software v. 2.7. The updated IAS resistance mutations list (March 2013) was considered for the analysis of resistance positions. Patients were followed testing viral load and immunologic parameters.

Results

Twenty four males and two females with a mean age of 43 years were included. Twenty‐one were nave for cART. At baseline, median HIV‐RNA was 4.57 log copies/mL (range 2.15–6.57) and CD4 count 315 cells/mcL (range 16–648). In 18 patients, NGS did not detect any additional variant relevant for the selected cART compared to population genotyping. In the remaining eight patients resistance conferring mutations to part of the ongoing regimen were detected. Single mutations E138K (two cases) and M184V in three distinct patients and V90I+G190E; M184V+A98S; Y215F+V118I+T215I; L210S+T215I+F227L; and A62V+D67G+K70N+188H in the remaining five subjects. In all cases, the mutation prevalence was inferior to 5%. The mean daily reduction of VL was −3759 copies/mL in patients without NGS detected mutations and −1045 copies/mL in those with mutations. The median KM estimates for reaching an HIV‐RNA blood level <50 copies/mL were 127 days and 161 days, respectively. One patient without baseline resistance selected for M184I+E138K+T215I (NGS) after four months of TDF/FTC/RPV therapy.

Conclusions

NGS detected low‐frequency HIV‐1 variants harbouring RT drug resistance mutations that could have affected the therapy outcome. However, viral decay in an early cART phase was not affected by the presence of resistant minority variants. The low prevalence of the detected mutation, the limited effect on the combination regimen and the potency of cART components could be possible explanations of our findings. Longer follow‐up and larger casuistries are needed to determine the clinical relevance of NGS in routine clinical practice and eventually define a clinically relevant mutations' prevalence.
144‐week outcomes of lopinavir/ritonavir (LPV/r)‐based first‐line ART in 1,409 HIV‐infected patients: data from the German STAR/STELLA cohort
Authors: Wolf Eva , Trein Andreas , Baumgarten Axel , Stephan Christoph , Jaeger Hans , Hillenbrand Heribert , Koeppe Siegfried , Lutz Thomas , Koenig Bettina , Stellbrink Hans‐Juergen
Published: November 2014

Introduction

STAR/STELLA is a prospective[TS1] cohort of HIV patients initiated on LPV/r‐based ART in routine clinical practice. Here, virologic/immunologic outcomes and safety data of LPV/r‐based first‐line ART over a period of 144 weeks are presented.

Methods

Analysis included ART‐naïve patients who started on LPV/r before July 2011 (i.e. patients with ≥144 weeks since ART initiation). Safety evaluation included adverse events (AEs), discontinuations (disc.) due to AEs, and symptoms assessed with the self‐report ACTG Symptom Distress Module (ASDM; high score=high distress).

Results

1409 patients were included (84% men; 76% on TDF+FTC), with a large proportion in advanced stages of HIV disease at ART initiation: 48% had a CD4 count <200/µL, 55% had HIV RNA levels >100,000 c/mL. 53% of patients (n=746) remained on LPV/r for at least 144 weeks. Time on drug was longer for patients initiated before 2008 than in subsequent years (HRadj, 1.2; 95% CI, 1.0–1.4; p=0.04; hazard ratio adjusted for CD4 <200/µL and HIV RNA >100,000 c/mL). Main reasons for d/c were: AEs (19.3%), patient wish (9.2%), virologic/immunologic failure (4.1%), and noncompliance (2.8%); 1.6% of patients died. By week 144, 33% of patients had >750 CD4/µL (Kaplan–Meier estimate): time to CD4 count >750 c/ µL, stratified by BL CD4 count, is shown in Figure 1.

ITT snapshot analysis of HIV RNA <50 c/mL at week 144 showed 51% responders (failure=d/c due to virologic/immunologic failure, AEs, noncompliance, death). In patients on LPV/r for 144 weeks, median CD4 change was +314/µL (IQR, 205–440/µL), 87% had HIV RNA levels <50 c/mL. In patients who discontinued therapy prior to week 144, 56% had an HIV RNA level <50 c/mL. In 51% of patients, ≥1 AE was reported (most commonly diarrhoea, 35%); 11% of patients had ≥1 AE of grade 3 or 4 (diarrhoea, 4.5%). In patients who remained on LPV/r based ART through 144 weeks, median ASDM score decreased significantly from 9 at BL (IQR, 3–21) to 2.5 at Week 144 (IQR, 0–8.5, p<0.001).

Conclusion

In the STAR/STELLA observational cohort, LPV/r‐based ART demonstrated good virologic outcomes and immune recovery in ART‐naïve patients over 144 weeks, with significant improvements in symptom distress. Over three years, <5% of patients discontinued LPV/r due to virologic/immunologic failure, and 19% of patients discontinued for tolerability reasons.
Analysis of Protein Composition Using Multidimensional Chromatography and Mass Spectrometry
Authors: Link Andrew J. , Washburn Michael P.
Published: November 2014

Multidimensional liquid chromatography of peptides produced by protease digestion of complex protein mixtures followed by tandem mass spectrometry can be coupled with automated database searching to identify large numbers of proteins in complex samples. These methods avoid the limitations of gel electrophoresis and in‐gel digestions by directly identifying protein mixtures in solution. One method used extensively is named Multidimensional Protein Identification Technology (MudPIT), where reversed‐phase chromatography and strong cation–exchange chromatography are coupled directly in a microcapillary column. This column is then placed in line between an HPLC and a mass spectrometer for complex mixture analysis. MudPIT remains a powerful approach for analyzing complex mixtures like whole proteomes and protein complexes. MudPIT is used for quantitative proteomic analysis of complex mixtures to generate novel biological insights. © 2014 by John Wiley & Sons, Inc.
Sampling of Intestinal Microbiota and Targeted Amplification of Bacterial 16S rRNA Genes for Microbial Ecologic Analysis
Authors: Tong Maomeng , Jacobs Jonathan P. , McHardy Ian H. , Braun Jonathan
Published: November 2014

Dysbiosis of host‐associated commensal microbiota is emerging as an important factor in risk and phenotype of immunologic, metabolic, and behavioral diseases. Accurate analysis of microbial composition and functional state in humans or mice requires appropriate collection and pre‐processing of biospecimens. Methods to sample luminal and mucosal microbiota from human or mouse intestines and to profile microbial phylogenetic composition using 16S rRNA sequencing are presented here. Data generated using the methods in this unit can be used for downstream quantitative analysis of microbial ecology. © 2014 by John Wiley & Sons, Inc.
Characterizing the convective boundary layer turbulence with a High Spectral Resolution Lidar
Authors: McNicholas Callie , Turner D. D.
Published: November 2014

High Spectral Resolution Lidar (HSRL) aerosol backscatter coefficient observations collected in Norman, Oklahoma, USA, between April and July 2012 were analyzed to characterize the turbulent fluctuations in the convective boundary layer (CBL). Seventeen cloud‐free 2 h periods, during which the CBL was quasi‐stationary in the late afternoon, were selected. Autocovariance techniques were applied to each 2 h period to derive vertical profiles of statistical moments and integral scale. The low random noise level in the HSRL allowed meaningful estimates of the variance, skewness (S), and kurtosis (K) of the aerosol backscatter field to be computed. The S profiles showed a transition from negative to positive just below the top of the CBL (zi); this suggests that there are relatively few narrow plumes of aerosol‐laden air being lofted from the CBL into the free troposphere (yielding positive S above zi) and similarly that there are some plumes of cleaner air descending from the free troposphere into the CBL (negative S below zi). Vertical profiles of K indicated that the distribution of aerosols transitioned from leptokurtic to platykurtic just above zi. However, the profile of K is not symmetric around zi; the turbulence is more intermittent above zi and below 0.8 zi, but the turbulent motions are relatively constant between 0.8 zi and zi. The relationship between S and K in the upper portion of the CBL and through the interfacial layer indicated that the distribution of turbulence is not Gaussian (i.e., S is 0 and K is 3) at any height.
All‐Metallic Vertical Transistors Based on Stacked Dirac Materials
Authors: Wang Yangyang , Ni Zeyuan , Liu Qihang , Quhe Ruge , Zheng Jiaxin , Ye Meng , Yu Dapeng , Shi Junjie , Yang Jinbo , Li Ju , Lu Jing
Published: November 2014

It is an ongoing pursuit to use metal as a channel material in a field effect transistor. All metallic transistor can be fabricated from pristine semimetallic Dirac materials (such as graphene, silicene, and germanene), but the on/off current ratio is very low. In a vertical heterostructure composed by two Dirac materials, the Dirac cones of the two materials survive the weak interlayer van der Waals interaction based on density functional theory method, and electron transport from the Dirac cone of one material to the one of the other material is therefore forbidden without assistance of phonon because of momentum mismatch. First‐principles quantum transport simulations of the all‐metallic vertical Dirac material heterostructure devices confirm the existence of a transport gap of over 0.4 eV, accompanied by a switching ratio of over 104. Such a striking behavior is robust against the relative rotation between the two Dirac materials and can be extended to twisted bilayer graphene. Therefore, all‐metallic junction can be a semiconductor and novel avenue is opened up for Dirac material vertical structures in high‐performance devices without opening their band gaps.
Pd Uptake and H2S Sensing by an Amphoteric Metal–Organic Framework with a Soft Core and Rigid Side Arms
Authors: Cui Jieshun , Wong Yan‐Lung , Zeller Matthias , Hunter Allen D. , Xu Zhengtao
Published: November 2014

Molecular components of opposite character are often incorporated within a single system, with a rigid core and flexible side arms being a common design choice. Herein, molecule L has been designed and prepared featuring the reverse design, with rigid side arms (arylalkynyl) serving to calibrate the mobility of the flexible polyether links in the core. Crystallization of this molecule with PbII ions led to a dynamic metal–organic framework (MOF) system that not only exhibits dramatic, reversible single‐crystal‐to‐single‐crystal transformations, but combines distinct donor and acceptor characteristics, allowing for substantial uptake of PdCl2 and colorimetric sensing of H2S in water.
Formation Maneuvering and Target Interception for Multi‐Agent Systems via Rigid Graphs
Authors: Cai Xiaoyu , de Queiroz Marcio
Published: November 2014

In this paper, we introduce control laws for multi‐agent formation maneuvering and target interception problems. In the target interception problem, we consider that the target velocity is unknown. Using a single‐integrator agent model, the proposed controls consist of a formation acquisition term, dependent on the graph rigidity matrix, and a formation maneuvering or target interception term. The control laws are only a function of the relative position of agents in an infinitesimally and minimally rigid graph, and either the desired maneuvering velocity of the formation or the target's relative position to the leader. The target interception control includes a continuous dynamic estimation term to identify the unknown target velocity. A Lyapunov‐like stability analysis is used to prove that the control objectives are met.
The Power of Social Influence on Estimation Accuracy
Authors: Gürçay Burcu , Mellers Barbara A. , Baron Jonathan
Published: November 2014

Research shows that crowds can provide more accurate estimates of uncertain quantities than individuals (Surowiecki, 2004). But little is known about how to organize crowd members to maximize accuracy. When should crowd members work independently, and when should they work collaboratively? We examined the effects of social influence on estimation accuracy, consensus, and confidence. Participants first made independent estimates of uncertain quantities, such as the percentage of U.S. deaths due to heart attacks or the height of the tallest building. Then, in some conditions, they interacted with others online. After the discussion, they made second independent estimates. Social interaction improved accuracy. Despite well‐known problems with groups, such as herding and free riding, discussion resulted in more accurate estimates and greater consensus relative to independent estimates. We offer a simple model that describes the process by which group discussion improves the estimates of uncertain quantities. Copyright © 2014 John Wiley & Sons, Ltd.
Die weltweit längste Textilbetonbrücke
Authors: Kulas Christian , Goralski Claus
Published: November 2014

Im baden‐württembergischen Albstadt wurde eine ältere Fußgängerbrücke aus Stahlbeton durch eine elegante Brücke aus Textilbeton ersetzt. Durch die Kombination von textilbewehrtem Beton mit einer Vorspannung ohne Verbund ließ sich eine für Betontragwerke außergewöhnliche Schlankheit erzielen. Die 97 m lange Brücke über die Bundesstraße B 463 besteht aus sechs Fertigteilen, die bei einer Elementlänge von 17,2 m eine Bauhöhe von nur 43 cm aufweisen. Im Beitrag werden Konstruktion, Bemessung und insbesondere das Schwingungsverhalten beschrieben. Des Weiteren wird über die Erfahrungen aus mehr als vier Betriebsjahren berichtet.

The worldwide longest textile‐reinforced concrete pedestrian bridge – Technical details and practical experiences

In Albstadt, Germany, the former pedestrian bridge, which was made of steel‐reinforced concrete, had to be replaced by a new construction made of textile‐reinforced concrete. Due to the combination of textile‐reinforcements and an unbonded prestressing a remarkable slenderness of the superstructure was achieved. The 97 m long bridge over the state road B 463 is built up of six prefabricated concrete elements, which have a maximum element length of 17.2 m while the construction height is only 43 cm. The article deals with details of the construction, the structural analysis and the dynamic behavour in particular. Furthermore, experiences after a lifetime of four years are reported.
Ermüdungsverhalten von Spanngliedern mit nachträglichem Verbund
Authors: Empelmann Martin , Remitz Jörn
Published: November 2014

Die Beurteilung der Ermüdungsfestigkeit von Spannstählen bei Bauwerken unter nicht vorwiegend ruhenden Einwirkungen gewinnt im Rahmen zunehmender Verkehrsbeanspruchungen, einer längeren Lebensdauer von Bauwerken sowie der Verwendung von innovativen und hochfesten Baustoffen weiter an Bedeutung. Insbesondere im eingebauten Zustand wird die Ermüdungsfestigkeit von Spannstählen aufgrund der komplexen Beanspruchungsverhältnisse von vielen Einflussfaktoren beeinträchtigt. Der Beitrag gibt einen Überblick über den derzeitigen Kenntnisstand zum Ermüdungsverhalten von Spannstählen. Dabei werden grundlegende Zusammenhänge der Reibermüdung erläutert und eine Datenbank über durchgeführte Untersuchungen aufgestellt. Die Ergebnisse werden hinsichtlich unterschiedlicher Einflussfaktoren ausgewertet und den WÖHLERdiagrammen des Eurocode 2 gegenübergestellt. Des Weiteren werden besondere Aspekte aus der Versuchsinterpretation und Nachweisführung diskutiert.

Fatigue behaviour of post‐tensioned tendons

The assessment of the fatigue strength of prestressing steel in structures under non‐predominantly static loads becomes more important within increasing traffic loads, longer life time of structures and the use of innovative and high‐strength materials. In particular, when installed, the fatigue strength of prestressing steel is affected by many factors due to the complex stress conditions. The article gives an overview of the current knowledge of the fatigue behavior of prestressing steels. The fundamental relationships of fretting fatigue are explained and a database is established after an evaluation of tests executed so far. The results are compared with the Woehler diagram of the Eurocode 2 and specific aspects of the experimental interpretation and verification are discussed.
The emerging functions of oligodendrocytes in regulating neuronal network behaviour
Authors: de Hoz Livia , Simons Mikael
Published: November 2014

Myelin is required for efficient nerve conduction, but not all axons are myelinated to the same extent. Here we review recent studies that have revealed distinct myelination patterns of different axonal paths, suggesting that myelination is not an all or none phenomenon and that its presence is finely regulated in central nervous system networks. Whereas powerful reductionist biology has led to important knowledge of how oligodendrocytes function by themselves, little is known about their role in neuronal networks. We still do not understand how oligodendrocytes integrate information from neurons to adapt their function to the need of the system. An intricate cross talk between neurons and glia is likely to exist and to determine how neuronal circuits operate as a whole. Dissecting these mechanisms by using integrative systems biology approaches is one of the major challenges ahead.
Enzyme‐linked immunosorbent assay by enhanced chemiluminescence detection for the standardization of estrogenic miroestrol in Pueraria candollei Graham ex Benth
Authors: Yusakul Gorawit , Udomsin Orapin , Tanaka Hiroyuki , Morimoto Satoshi , Juengwatanatrakul Thaweesak , Putalun Waraporn
Published: November 2014

Miroestrol (ME) is a potent phytoestrogen from the P. candollei tuberous root. It has been approved for use in clinical trials due to its beneficial effect on disorders associated with estrogen deficiency. To ensure medical efficacy and safety, high performance analytical methods for ME analysis are required to standardize products from the P. candollei root. An enhanced chemiluminescence enzyme‐linked immunosorbent assay (ECL‐ELISA) was developed and validated using a polyclonal antibody against ME and a chemiluminescent system of luminol–H2O2–horseradish peroxidase‐4‐(1‐imidazolyl) phenol. The ECL‐ELISA system exhibited linearity over a concentration range of 0.31–10.00 ng mL−1, for which the relative standard variation (%RSD) was less than 10% for both intra‐ and interplate determinations. The ECL‐ELISA is reliable for the determination of ME as reflected by the high recovery percentage (101.22–103.06%). As a comparative analysis, the ME content in each sample determined by ECL‐ELISA was correlated with high coefficients of determination with colorimetric ELISA (R2 = 0.998) and high performance liquid chromatography (HPLC) (R2 = 0.998) methods. The ECL‐ELISA method could be applied to all of the commercial products containing P. candollei root, when the products contain between 0.706 ± 0.046 and 13.123 ± 0.794 µg g−1 dry wt. of ME. This method is useful as a high performance analytical method for the quantity control of ME in raw materials and end products at both the research and industrial levels. Copyright © 2014 John Wiley & Sons, Ltd.
An Enolate‐Mediated Organocatalytic Azide–Ketone [3+2]‐Cycloaddition Reaction: Regioselective High‐Yielding Synthesis of Fully Decorated 1,2,3‐Triazoles
Authors: Shashank Adluri B. , Karthik S. , Madhavachary R. , Ramachary Dhevalapally B.
Published: November 2014

An enolate‐mediated organocatalytic azide–ketone [3+2]‐cycloaddition (OrgAKC) reaction of a variety of enolizable arylacetones and deoxybenzoins with aryl azides was developed for the synthesis of fully decorated 1,4‐diaryl‐5‐methyl(alkyl)‐1,2,3‐triazoles in excellent yields with high regioselectivity at 25 °C for 0.5–6 h. This reaction has an excellent outcome with reference to reaction rate, yield, regioselectivity, operation simplicity, and availability of substrates and catalyst. This reaction has advantages over the previously known metal‐mediated reactions.
A Highly Selective and Turn‐on Fluorescent Probe for Fe3+ Ion Based on Perylene Tetracarboxylic Diimide
Authors: Lin Jinbin , Zhu Chunhui , Liu Xiaoqiong , Chen Bo , Zhang Yiyang , Xue Jinping , Liu Jianyong
Published: November 2014

We have demonstrated a turn‐on fluorescent sensor 6 for detection of Fe3+ based on photo‐induced electron transfer (PET) mechanism. The probe comprises a perylene tetracarboxylic diimide (PDI) fluorophore and two bis((1,2,3‐triazol‐4‐yl)methyl)amine (DTA) moieties as the metal ion receptors. It exhibits high selectivity toward Fe3+ over various other metal ions in CH3CN/H2O (1:1, V/V). The binding stoichiometry for 6‐Fe3+ complexes has been determined to be 1:2 by a Job plot of fluorescence. The association constant between 6 and Fe3+ was estimated to be 1.04×1010 (mol/L)−2 by Benesi‐Hildebrand equation.
Dye‐Sensitized Solar Cell Counter Electrodes Based on Carbon Nanotubes
Authors: Hwang Seunghwa , Batmunkh Munkhbayar , Nine Md J. , Chung Hanshik , Jeong Hyomin
Published: November 2014

Dye‐sensitized solar cells (DSSCs) have received significant attention from the scientific community since their discovery in 1991. However, the high cost and scarcity of platinum has motivated researchers to seek other suitable materials for the counter electrode of DSSCs. Owing to their exceptional properties such as high conductivity, good electrochemical activity, and low cost, carbon nanotubes (CNTs) have been considered as promising alternatives to expensive platinum (Pt) in the counter electrode of DSSCs. Herein, we provide a Minireview of the CNTs use in the counter electrode of DSSCs. A brief overview of Pt‐based counter electrodes is also discussed. Particular attention is given to the recent advances of counter electrodes with CNT‐based composite structures.
Institutionalizing Sustainable Conflict Management in Organizations: Leaders, Networks, and Sensemaking
Authors: Liu Leigh Anne , Inlow Lin , Feng Jing Betty
Published: November 2014

We investigated the process and outcomes of a systematic approach to institutionalize conflict management in a large public nonprofit organization. Using longitudinal and multilevel field data, we were able to identify the effects of the institutionalization process from multiple perspectives. We hypothesized and found the combination of three critical social factors—leadership, construction and maintenance of social networks, and the sensemaking processes—in the diffusion of both codified and tacit knowledge about conflict management. Also, social construction supplements structural factors in the institutionalization process of conflict management practices.
A randomized, double‐blind, placebo‐controlled, phase II clinical trial to investigate the efficacy and safety of oral DA‐1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise
Authors: Jung Chang Hee , Park Cheol‐Young , Ahn Kyu‐Joeng , Kim Nan‐Hee , Jang Hak‐Chul , Lee Moon‐Kyu , Park Joong‐Yeol , Chung Choon‐Hee , Min Kyung‐Wan , Sung Yeon‐Ah , Park Jeong‐Hyun , Kim Sung Jin , Lee Hyo Jung , Park Sung‐Woo
Published: November 2014

Background

DA‐1229 is a novel, potent and selective dipeptidyl peptidase‐4 (DPP‐IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA‐1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise.

Methods

We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m2). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12‐week active treatment period: placebo, 2.5, 5 or 10 mg of DA‐1229.

Results

All three doses of DA‐1229 significantly reduced HbA1c from baseline compared to the placebo group (−0.09 in the placebo group vs. −0.56, −0.66 and −0.61% in 2.5, 5 and 10‐mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β‐cell, the insulinogenic index, 2‐h oral glucose tolerance test (OGTT) C‐peptide and post‐OGTT C‐peptide area under the curve (AUC)0–2h, significantly improved with DA‐1229 treatment. The incidence of adverse events was similar between the treatment groups and DA‐1229 did not affect body weight or induce hypoglycaemic events.

Conclusions

DA‐1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β‐cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd.
Native PAGE to study the interaction between the oncosuppressor p53 and its protein ligands
Authors: Lamberti Anna , Sgammato Roberta , Desiderio Doriana , Punzo Chiara , Raimo Gennaro , Novellino Ettore , Carotenuto Alfonso , Masullo Mariorosario
Published: November 2014

In the present study, we investigated a new approach for studying the interaction between p53 and MDM2/X (where MDM is murine double minute protein). The method is based on the different mobility between the interacting domains of the oncosuppressor p53 and its protein ligands MDM2/X on polyacrylamide gels under native conditions. While the two proteins MDM2/X alone were able to enter the gel, the formation of a binary complex between p53 and MDM2/X prevented the gel entry. The novel technique is reliable for determining the different affinity elicited by MDM2 or MDMX toward p53, and can be useful for analyzing the dissociation power exerted by other molecules on the p53–MDM2/X complex.
5‐Aminolevulinic acid promotes callus growth and paclitaxel production in light‐grown Taxus cuspidata suspension cultures
Authors: Yamamoto Shinjiro , Hayashi Shuhei , Furusaki Shintaro , Shioya Suteaki
Published: November 2014

Cultured plant cells generally produce low levels of secondary metabolites, and elicitors of secondary metabolites usually inhibit callus growth. The aim of this study was to determine the effect of 5‐aminolevulinic acid (ALA), a chlorophyll precursor that promotes plant growth, on callus induction from leaves of Taxus cuspidata, and on callus growth on solid medium. ALA at 0.76, 7.6, and 76 μM had similar effects on callus induction and growth, while ALA at 760 μM had negative effects. Next, the effects of ALA concentrations on callus growth and paclitaxel production in suspension cultures in the dark were evaluated. The results showed that 0.76 and 7.6 μM ALA stimulated growth and paclitaxel production, while 76 μM ALA had negative effects. ALA is thought to promote cellular activity under light conditions. Therefore, the effects of light intensity on callus growth and paclitaxel production in the presence of ALA were evaluated. Our results showed that the best conditions for callus growth and paclitaxel production were 7.6 μM ALA under photosynthetically active radiation of 12 μmol photons m−2 s−1. Callus growth and paclitaxel production were inhibited under stronger light (24 μmol photons m−2 s−1). Together, these results show that ALA promoted callus growth and the production of paclitaxel by light‐grown cultured T. cuspidata cells.
Discussion on ‘relaxation method for pounding action between adjacent buildings at expansion joint’ by H. Takabatake, M. Yasui, Y. Nakagawa and A. Kishida
Authors: Khatiwada Sushil , Chouw Nawawi , Larkin Tam
Published: November 2014

The paper under discussion presents a detailed study on the reduction of pounding force on buildings due to expansion joints being filled with rubber. From shake table experiments and numerical simulations, the authors of the paper concluded that the rubber can reduce the maximum pounding force and hence the pounding damage to buildings. However, the writers of this short communication observed some significant issues in the experimental results as well as the numerical simulations. These observations are presented and raise questions about the validity of the results and the subsequent conclusions. Copyright © 2014 John Wiley & Sons, Ltd.
Physical activity in the elderly is associated with improved executive function and processing speed: the LADIS Study
Authors: Frederiksen Kristian Steen , Verdelho Ana , Madureira Sofia , Bäzner Hansjörg , O'Brien John T. , Fazekas Franz , Scheltens Philip , Schmidt Reinhold , Wallin Anders , Wahlund Lars‐Olof , Erkinjunttii Timo , Poggesi Anna , Pantoni Leonardo , Inzitari Domenico , Waldemar Gunhild ,   on behalf of the LADIS Study
Published: November 2014

Objectives

Physical activity reduces the risk of cognitive decline but may affect cognitive domains differently. We examined whether physical activity modifies processing speed, executive function and memory in a population of non‐dementia elderly subjects with age‐related white matter changes (ARWMC).

Methods

Data from the Leukoaraiosis And DISability (LADIS) study, a multicenter, European prospective cohort study aimed at examining the role of ARWMC in transition to disability, was used. Subjects in the LADIS study were clinically assessed yearly for 3 years including MRI at baseline and 3‐year follow‐up. Physical activity was assessed at baseline, and cognitive compound scores at baseline and 3‐year assessment were used.

Results

Two‐hundred‐eighty‐two subjects (age, y (mean (SD)): 73.1 (±5.1); gender (f/m): 164/118); MMSE (mean (SD)): 28.3 (±1.7)) who had not progressed to MCI or dementia, were included. Multiple variable linear regression analysis with baseline MMSE, education, gender, age, stroke, diabetes and ARWMC rating as covariates revealed that physical activity was associated with better scores at baseline and 3‐year follow‐up for executive function (baseline: β: 0.39, 95% CI: 0.13–0.90, p = 0.008; follow‐up: β: 0.24, 95% CI: 0.10–0.38, p = 0.001) and processing speed (baseline: β: 0.48, 95% CI: 0.14–0.89, p = 0.005; follow‐up: β: 0.15, 95% CI: 0.02–0.29, p = 0.02) but not memory. When including baseline cognitive score as a covariate in the analysis of 3‐year follow‐up scores, executive function remained significant (β: 0.11, 95% CI: 0–0.22, p = 0.04).

Conclusion

Our findings confirm previous findings of a positive effect of physical activity on cognitive functions in elderly subjects, and further extends these by showing that the association is also present in patients with ARWMC. Copyright © 2014 John Wiley & Sons, Ltd.
Reconsidering the Role of HR in M&As: What Can Be Learned From Practice
Authors: Bagdadli Silvia , Hayton James C. , Perfido Osvaldo
Published: November 2014

Mergers and acquisitions (M&As) offer an important tool for rapid organizational growth, acquisition of new knowledge and capabilities, and entry into new markets at home or abroad. Although the importance of the involvement of the human resource management function has been widely extolled, evidence for the level of involvement remains limited. A significant gap in our understanding is created by the observation that not all M&As are motivated by the same objectives. We explore the significance of different forms of M&A for the scope and intensity of involvement of the human resource management function by examining a set of three cases of different M&As conducted by a single firm in Italy. The cases provide evidence that we should expect HR functional involvement to vary across the type of M&A. We offer a conceptual framework with testable propositions for scholars interested in further exploring these relationships. © 2014 Wiley Periodicals, Inc.
Effects of endogenous and exogenous progesterone on emotional intelligence in cocaine‐dependent men and women who also abuse alcohol
Authors: Milivojevic Verica , Sinha Rajita , Morgan Peter T. , Sofuoglu Mehmet , Fox Helen C.
Published: November 2014

Objective

As sex differences in substance dependence may impinge upon the perception and regulation of emotion, we assess emotional intelligence (EI) as a function of gender, menstrual cycle (MC) phase and hormonal changes in early abstinent cocaine‐dependent individuals who abuse alcohol (CDA).

Methods

Study 1: The Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT) was administered to 98 CDA (55 M/43 F) and 56 healthy (28 M/28 F) individuals. Performance in women was also assessed by MC phase. Study 2: The MSCEIT was administered to 28 CDA (19 M/9 F) who received exogenous progesterone (400 mg/day) versus placebo for 7 days (study 2).

Results

Study 1: Healthy females were better than healthy males at facilitating thought and managing emotions. This gender discrepancy was not observed in the CDA group. Additionally, all women in the high compared with the low progesterone phase of their MC were better at managing their emotions. Study 2: Exogenous progesterone improved ability to facilitate thought in both males and females.

Conclusions

CDA women may be vulnerable to difficulties managing and regulating emotions. Gonadal hormones may contribute to this gender effect, as increases in both endogenous and exogenous progesterone improved selective aspects of EI. Copyright © 2014 John Wiley & Sons, Ltd.
Microstructural analysis of three‐dimensional canal network in the rabbit lumbar vertebral endplate
Authors: Yamaguchi Tomonori , Goto Shota , Nishigaki Yasuhiro , Orías Alejandro A. Espinoza , Bae Won C. , Masuda Koichi , Inoue Nozomu
Published: November 2014

Insufficient nutrient supply through vertebral canal structures to the intervertebral disc (IVD) has been considered as an important contributor for disc degeneration. Despite previous canal structure characterization studies using histology, scanning electron microscopy, and angiography, among others, their three‐dimensional (3D) topology inside the vertebral endplate remains poorly understood. This study aims to characterize the 3D canal structure in the rabbit lumbar vertebral endplate using micro computed tomography (μCT). Vertebral endplates were imaged using high‐resolution μCT with 1.4 × 1.4 × 1.8 μm voxel size. Diameter, length, orientation, and depth starting from the vertebral endplate surface were analyzed for each canal using individual 3D canal models from the vertebral endplate scans. In the layer underneath the vertebral endplate, at a mean depth of 76.2 μm, longitudinally‐oriented relatively short‐length (57.6 μm) and small diameter (45.7 μm) canals were dominant. Large‐scale canals with a mean diameter of 152.1 μm running parallel to the endplate surface were isolated at the depth of 224.1 μm. These canals were connected to both IVD and bone marrow spaces through vertically oriented canals. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:270–276, 2015.
Hypolipidemic activity of common (Fagopyrum esculentum Moench) and tartary (Fagopyrum tataricum Gaertn.) buckwheat
Authors: Tomotake Hiroyuki , Kayashita Jun , Kato Norihisa
Published: November 2014

Buckwheat grain has well‐balanced nutritional value, whereas its digestibility is relatively low. This review summarizes recent advances in studies on the hypolipidemic activity of buckwheat. The most remarkable function is a powerful hypocholesterolemic activity of buckwheat protein in rats, which is far stronger than that of soy protein. The cholesterol‐lowering effect is mediated by mechanisms involving higher excretion of fecal sterols and lower digestibility of buckwheat protein. The insoluble fraction of buckwheat protein associates with cholesterol and reduces micelle cholesterol uptake in caco‐2 cells. Furthermore, consumption of buckwheat protein suppresses cholesterol‐induced gallstones and body fat in rodents. Buckwheat sprouts also have hypolipidemic activity in rats or type 2 diabetic mice. Tartary buckwheat bran extract reduced the serum level of total cholesterol and triglyceride in hyperlipidemic rats. The consumption of buckwheat seed reduced low‐density lipoprotein cholesterol in the pastureland Mongolian population. Taken together, buckwheat may be beneficial for prevention of hyperlipidemia. © 2014 Society of Chemical Industry
Pure Air for Ultrashort‐Pulse Lasers
Authors: Jakschik Stefan , Türschmann Volker
Published: November 2014

The ultrashort‐pulse laser provides a precision and quality that have been previously unknown. This is a fact. And because of new applications, this relatively young technology is becoming more and more established in industry. What has been mostly ignored, however, is the question of which particles are entering the environment through the use of this laser. ULT has got to the bottom of this issue.
Adaptive Processes for the Aircraft Engines of Tomorrow
Authors: Fecht Nikolaus
Published: November 2014

Among the public's favorites at the ILA Berlin Airshow were the future “stars in the heavens“, such as the Airbus A350 XWB. Rather inconspicuous, but equally spectacular were the manufacturing technologies applied to create more efficient jet engines, which the Fraunhofer researchers, represented by the Innovation Cluster AdaM, displayed in Berlin.
Land Suitability Assessment for Afforestation with Elaeagnus Angustifolia L. in Degraded Agricultural Areas of the Lower Amudarya River Basin
Authors: Dubovyk Olena , Menz Gunter , Khamzina Asia
Published: November 2014

Degradation of irrigated croplands in arid regions is of great environmental concern worldwide. Based on a series of field trials, afforestation with well‐adapted tree species was evaluated as a viable option for the cropland rehabilitation in the lower reaches of the Amudarya River basin in Uzbekistan. Our aim was to extend available site‐specific information for the entire regional landscape and provide spatially explicit guidance in support of afforestation land rehabilitation efforts. To this end, a geographic information system—based multicriteria decision‐making approach has been developed for assessing the suitability of degraded irrigated cropland for introducing plantations of Elaeagnus angustifolia L. This approach utilized expert knowledge, fuzzy logic, and a weighted linear combination to produce an afforestation land suitability map. Overall, 75 287 ha of degraded croplands (18% of the irrigated cropland area) was identified as suitable for introduction of E. angustifolia. We also conclude that irrigation water supply and groundwater table depth are the critical factors determining the suitability of degraded irrigated land. These findings improve an understanding of the spatial variability of areas suitable for the initiation of agroforests and support better informed decisions on cropland rehabilitation. Copyright © 2014 John Wiley & Sons, Ltd.