bluuebunny/crossref_metadata_2025 huggingface dataset:
Scanning Ion Conductance Microscopic Study for Cellular Uptake of Cationic Conjugated Polymer Nanoparticles
Authors: Shan Yuping , Panday Namuna , Myoung Yong , Twomey Megan , Wang Xuewen , Li Wenzhi , Celik Emrah , Moy Vincent , Wang Hongda , Moon Joong Ho , He Jin
Published: January 2016

Positively charged conjugated polymer nanoparticles (CPNs) are emerging biomaterials exhibiting high levels of cellular entry. High rate of cellular entry efficiency is believed that the amphiphilic CPNs interact efficiently with the negatively charged hydrophobic cellular membranes. For the first time, the cell surface morphological changes of human cervical cancer cells treated with CPNs using a scanning probe microscopy technique, scanning ion conductance microscopy (SICM) are imaged. After 1 h of CPN incubation, distinct changes are observed in cell surface morphology such as interconnected protrusions and pits with sub‐micrometer sizes, which are not observed from cells treated with positively charged polyethyleneimine (PEI) under the same treatment conditions. The change on cell surface morphology is quantified by surface roughness ratio, which is increased as CPN concentration increases, while the ratio first increases and then decreases as the incubation time increases. These results suggest that cells respond actively toward CPN with both positive charges on the side chain and the hydrophobicity from rigid aromatic backbone, which leads to subsequent endocytosis. In conclusion, it is demonstrated that SICM is a suitable imaging technique to reveal the dynamic alternations on the cell surface morphology at the early stage of nanoparticles endocytosis with high resolution.

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Three‐Layered PCL Grafts Promoted Vascular Regeneration in a Rabbit Carotid Artery Model
Authors: Wang Kai , Zheng Wenting , Pan Yiwa , Ma Shaoyang , Guan Yong , Liu Ruming , Zhu Meifeng , Zhou Xin , Zhang Jun , Zhao Qiang , Zhu Yan , Wang Lianyong , Kong Deling
Published: January 2016

In this study, a three layered poly (ε‐caprolactone) (PCL) graft (tPCL) was fabricated by electrospinning PCL and electrospraying poly (ethylene oxide) (PEO), which has a thin dense inner layer, a loose middle layer, and a dense outer layer. Regular PCL grafts (rPCL) with only a dense layer were used as control. In vivo evaluation was performed in rabbit carotid artery. Enhanced cell infiltration, rapid regeneration of endothelium and smooth muscle layers, and increased elastin deposition were observed within the tPCL graft wall. After 3 months, tPCL grafts showed faster PCL degradation than the rPCL grafts. Infiltrated macrophages in the tPCL grafts secreted higher level of monocyte chemoattractant protein‐1 (MCP‐1) and vascular endothelial growth factor (VEGF) which enhanced vascular regeneration. In conclusion, the tPCL graft may be a useful vascular prosthesis and worth for further investigation.

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Manufacturing process development of a precision rapid tooling with high‐aspect‐ratio micro‐sized features
Authors: Kuo C.‐C. , Zhuang B.‐C.
Published: January 2016

The high‐aspect‐ratio elements are widely employed for chemical sensors, microfluidics and medical imaging devices. To enhance the competitiveness in the market of elements with high‐aspect‐ratio microstructures, a cost‐effective method for fabricating molds with high‐aspect‐ratio microstructures was proposed. In order to manufacture the second rubber mold, low‐temperature plasma were used to change the surface characteristics of the rubber mold to avoid using the release agents in the manufacturing process. It was found that the aluminum (Al)‐filled epoxy resin mold with the aspect ratio of 20 : 1 can be carried out in about three days. Replication rates of a precision rapid tooling with high‐aspect‐ratio micro‐sized features around 97 % can be obtained. The total fabrication cost savings for fabricating a SU‐8 microelement with the aspect ratio of 20 : 1 about 71 % can be obtained.
Microstructure and mechanical properties of Mg–6Sn and Mg–6Zn alloys prepared by different processing techniques: a comparative study
Authors: El Mahallawy N. , Ahmed Diaa A. , Akdesir M. , Palkowski H.
Published: January 2016

The microstructure and mechanical properties of Mg–6Sn and Mg–6Zn are investigated and compared in cast/heat treated, rolled and extruded conditions. Compared to the heat treated alloys, the grain size of both alloys decreases while the volume fraction of precipitates increases by rolling and extrusion in Mg–6Sn alloy at 350 ºC due to dynamic recrystallization and dynamic precipitation of intermetallic phases. Zinc has a stronger grain refining effect than tin in the heat treated alloys while the opposite effect is found in the rolled and extruded alloys.

For the heat treated alloys the Mg–6Sn the strength reached 158.7 MPa with elongation 5.2% while Mg–6Zn exhibited a higher strength of 183.7 MPa and 8.4% elongation. In rolled condition the strength of Mg–6Sn reached 224 MPa with 1.6% elongation while Mg–6Zn exhibited a lower strength of 124 MPa and a lower ductility of 0.5% elongation due to susceptibility to hot shortness. Extrusion of Mg–6Sn alloy resulted in the maximum attained strength of 281 MPa and an elongation of 6.1% while Mg–6Zn cracked during extrusion due to hot shortness. The results obtained are discussed with respect to microstructure evolution in both alloys.
Mitochondrial DNA copy number in whole blood and glioma risk: A case control study
Authors: Shen Jie , Song Renduo , Lu Zhimin , Zhao Hua
Published: January 2016

Alterations in mitochondrial DNA (mtDNA) copy number are observed in human gliomas. However, whether variations in mtDNA copy number in whole blood play any role in glioma carcinogenesis is still largely unknown. In current study with 395 glioma patients and 425 healthy controls, we intended to investigate the association between mtDNA copy number in whole blood and glioma risk. Overall, we found that levels of mtDNA copy number were significantly higher in glioma cases than healthy controls (mean: 1.48 vs. 1.32, P < 0.01). In both cases and controls, levels of mtDNA copy number were inversely correlated with age (P < 0.01, respectively). And in cases, newly diagnosed, glioblastoma (GBM), and high grade glioma patients had significantly lower mtDNA copy number than their counterparts (P = 0.02, P < 0.01, and P = 0.04, respectively). In the multivariate analysis, elevated mtDNA copy number levels were associated with a 1.63‐fold increased risk of glioma (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.23–2.14). In further quartile analysis, study subjects who had highest levels of mtNDA copy number had 1.75‐fold increased risk of gliomas (adjOR = 1.75, 95%CI = 1.18–2.61). In brief, our findings support the role of mtDNA copy number in the glioma carcinogenesis. © 2016 Wiley Periodicals, Inc.
Suppression of phospho‐p85α–GTP‐Rac1 lipid raft interaction by bichalcone analog attenuates cancer cell invasion
Authors: Lu Hui‐Li , Chen Shih‐Shun , Hsu Wen‐Tung , Lu Yao‐Cheng , Lee Chuan‐Chun , Wu Tian‐Shung , Lin Meng‐Liang
Published: January 2016

The p85α subunit of phosphatidylinositol 3‐kinase (PI3K) acts as a key regulator of cell proliferation and motility, which mediates signals that confer chemoresistance to many human cancer cells. Using small interfering RNAs against matrix metalloproteinase‐2 (MMP‐2) and the MMP‐2 promoter‐driven luciferase assay, we showed that the new synthetic bichalcone analog TSWU‐CD4 inhibits the invasion of human cancer cells by down‐regulating MMP‐2 expression. Treatment with TSWU‐CD4 inhibited MMP‐2 expression and cell invasion, which were restored by ectopic wild type (wt) p85α or a constitutively active form of MAPK kinase 3 (CA MKK3), CA MKK6, or CA p38α mitogen‐activated protein kinase (MAPK). The attenuated formation of lipid raft‐associated phospho (p)‐p85α–GTP‐Rac1 complexes, protein kinase B (Akt) Ser 473 phosphorylation, and cell invasion by TSWU‐CD4 was reversed by overexpression of wt p85α or the p85α Brc‐homology (BH) domain. The ectopic expression of CA Rac1L61 (but not wt Rac1) could overcome the suppression of Ser 473 phosphorylation, lipid raft association of Akt, the interaction between GTP‐bound Rac1 and p85α in lipid rafts, and cell invasion by TSWU‐CD4. The involvement of Akt activity in the functions of NF‐κB‐mediated MMP‐2 was further confirmed through the attenuation of Akt phosphorylation signaling using the Akt‐specific inhibitor MK‐2206 and ectopic expression of NF‐κB p65. Collectively, the inhibitory effect of TSWU‐CD4 on cancer cell invasion was likely to suppress the p‐p85α–GTP‐Rac1 interaction in lipid rafts by targeting the p85α BH domain, which resulted in the suppression of MMP‐2 expression via the PI3K–Akt‐mediated ERK–MKK3/MKK6–p38 MAPK‐NF‐κB signaling pathway. © 2016 Wiley Periodicals, Inc.
Coil‐to‐coil physiological noise correlations and their impact on functional MRI time‐series signal‐to‐noise ratio
Authors: Triantafyllou Christina , Polimeni Jonathan R. , Keil Boris , Wald Lawrence L.
Published: January 2016

Purpose

Physiological nuisance fluctuations (“physiological noise”) are a major contribution to the time‐series signal‐to‐noise ratio (tSNR) of functional imaging. While thermal noise correlations between array coil elements have a well‐characterized effect on the image Signal to Noise Ratio (SNR0), the element‐to‐element covariance matrix of the time‐series fluctuations has not yet been analyzed. We examine this effect with a goal of ultimately improving the combination of multichannel array data.

Theory and Methods

We extend the theoretical relationship between tSNR and SNR0 to include a time‐series noise covariance matrix Ψt, distinct from the thermal noise covariance matrix Ψ0, and compare its structure to Ψ0 and the signal coupling matrix SSH formed from the signal intensity vectors S.

Results

Inclusion of the measured time‐series noise covariance matrix into the model relating tSNR and SNR0 improves the fit of experimental multichannel data and is shown to be distinct from Ψ0 or SSH.

Conclusion

Time‐series noise covariances in array coils are found to differ from Ψ0 and more surprisingly, from the signal coupling matrix SSH. Correct characterization of the time‐series noise has implications for the analysis of time‐series data and for improving the coil element combination process. Magn Reson Med 76:1708–1719, 2016. © 2016 International Society for Magnetic Resonance in Medicine
The Workplace Experiences of Women with Fibromyalgia
Authors: Juuso Päivi , Skär Lisa , Sundin Karin , Söderberg Siv
Published: January 2016

Purpose

Fibromyalgia (FM) is a common pain syndrome that mostly affects women. Chronic pain and other symptoms often chalenge work for women with FM. This study aimed to explore how women with FM experience their work situations.

Method

A purposive sample of 15 women with FM was interviewed with in‐depth qualitative interviews. Data were analysed using a hermeneutic approach.

Results

The results revealed that women with FM experienced incapacity to work as they had previously and eventually accepted that their work life had changed or reached its end. Since their work had great significance in their lives, feelings of loss and sorrow were common. Women who were working, unemployed, or on sick leave described feelings of fear for their future work situations.

Conclusions

Women with FM greatly value their work. Their wish to perform work as before is however, not consistent with their abilities. As such, women with FM need support in continuing to work for as long as possible, after which they need support in finding new values in life.
Scapulothoracic Muscle Strength Changes Following a Single Session of Manual Therapy and an Exercise Programme in Subjects with Neck Pain
Authors: Petersen Shannon , Domino Nathan , Postma Christopher , Wells Cody , Cook Chad
Published: January 2016

Introduction

Scapulothoracic muscle weakness has been associated with neck pain (NP). Little evidence exists regarding lower trapezius (LT), middle trapezius (MT) and serratus anterior (SA) strength in this population. LT strength changes have been observed following thoracic manipulation in healthy subjects. The purpose of the present study was to examine scapulothoracic strength changes following cervical manipulation in subjects with NP.

Methods

Twenty‐two subjects with NP and 17 asymptomatic control (AC) subjects underwent strength testing of the LT, MT and SA using a hand‐held dynamometer. Subjects with NP were treated with passive intervertebral neck manipulation and neck range of motion exercises. The AC group received no intervention. Strength testing was repeated after manipulation, then 48 and 96 hours later. Change scores were calculated for strength over time. Paired t‐tests were done for strength change between painful and non‐painful sides in the NP group. Independent t‐tests were done for strength change between the NP group and AC group.

Results

There was no significant difference between groups for age, gender, hand dominance or body mass index. Mean (standard deviation) symptom duration for subjects in the NP group was 43.27 (62.71) months. There was no significant difference in strength change over time between painful and non‐painful sides in the NP group for any muscle; however, there was a significant difference in strength change over time between those in the NP group and AC group for the LT (p < 0.01), SA (p < 0.01) and MT (p < 0.01).

Discussion

Scapulothoracic muscle strength improvements were observed in both extremities following passive intervertebral neck manipulation and neck range of motion exercises. Improvements lasted up to 96 hours following manipulation, even though no strengthening exercises were prescribed.

Conclusions

Manipulation and range of motion should be considered as a component of intervention programmes for patients with NP and scapulothoracic muscle weakness. Future studies should compare manipulation alone to exercise alone to determine impact on strength. Copyright © 2016 The Authors Musculoskeletal Care Published by John Wiley & Sons Ltd.
Gute Aussichten für Verkäufer
Authors: Schneider Bernd
Published: January 2016

Niedrige Zinsen und hohe Kapitalverfügbarkeit bei geringem Angebot attraktiver Investitionsobjekte sorgten im Jahr 2015 für hohe Preise bei Chemietransaktionen. In einem derartigen Umfeld bieten sich Verkäufern – insbesondere in Subsegmenten mit strukturellen Herausforderungen wie den Pigmenten, Farben und Lacken – wertmaximierende Möglichkeiten zur strategischen Neupositionierung.
ORCID – Offener Standard zur Vernetzung von Forschenden
Authors: Pampel Heinz , Fenner Martin
Published: January 2016

Das internationale ORCID‐Konsortium vernetzt Publizierende mit ihren Aufsätzen und Forschungsdaten über eine eindeutige ID. Bereits über 1,6 Millionen Forschende besitzen eine solche Kennung.
Der Duft von Weihrauch
Authors: Niebler Johannes , Büttner Andrea
Published: January 2016

Weihrauch begleitet als kostbares Räucherwerk rituelle Handlungen seit Jahrtausenden. Neue Untersuchungen haben jetzt die sortenspezifischen flüchtigen Inhaltsstoffe umfassend charakterisiert und den Geruch unter die Lupe genommen.
Patient factors associated with onabotulinum toxin A treatment outcome in women with detrusor overactivity
Authors: Owen Rhiannon K. , Abrams Keith R. , Mayne Christopher , Slack Mark , Tincello Douglas G.
Published: January 2016

Objective

To evaluate potential predictors of non‐response to treatment with 200U onabotulinum toxin A (onaBoNTA) in women with refractory detrusor overactivity (DO).

Subjects and Methods

A secondary analysis of a randomized trial of 200U onaBoNTA versus placebo in women with refractory DO analyzed baseline and 6 week follow‐up data. Univariate and multivariate logistic regression were used to assess demographic factors and baseline clinical parameters on non‐response to treatment defined as 20% or less improvement in urinary urgency and leakage episodes, 10% or less in voiding frequency, not achieving continence, and “no change” or worse on PGI‐I score at 6 weeks.

Results

One Hundred and twenty‐two women were included. Twenty‐nine (23.8%), 24 (19.7%), and 19 (15.6%) were non‐responders to treatment for urgency, voiding, and leakage episodes, respectively. Fifty‐nine (48.4%) failed to achieve continence, and 28 (23%) were non‐responders on the PGI‐I scale. Smoking status (OR: 2.89 95%CI 1.08, 7.73, P = 0.034) predicted non‐response in urgency episodes, and higher baseline leakage episodes (OR: 1.17 95%CI 1.04, 1.31, P = 0.007) predicted non‐response in achieving continence. Increasing age (OR 1.04, 95%CI 1.0, 1.09, P = 0.063) and body mass index (BMI) (OR 1.07, 95%CI 1.0, 1.16, P = 0.065) showed marginal associations with non‐response on the PGI‐I scale.

Conclusion

onaBoNTA is an effective treatment for refractory DO, but some fail to respond. For identification of women at risk, our data indicate smokers should be advised of a lesser chance of successful treatment. Older women, those with high BMI and with more severe leakage also have a higher risk of failure. Neurourol. Urodynam. 36:426–431, 2017. © 2016 Wiley Periodicals, Inc.
Natural history of non‐neurogenic overactive bladder and urinary incontinence over 5 years in community‐dwelling older men: The concord health and aging in men project
Authors: Noguchi Naomi , Chan Lewis , Cumming Robert G. , Blyth Fiona M. , Handelsman David J. , Waite Louise M. , Le Couteur David G. , Naganathan Vasi
Published: January 2016

Aims

To describe the natural history of non‐neurogenic overactive bladder (OAB) and urgency incontinence in community‐dwelling older men.

Methods

A representative sample of 1,705 community‐dwelling men aged 70 and older in a defined geographic area of Sydney, Australia, had their urinary symptoms assessed using the International Prostate Symptom Scores (IPSS) and the International Consultation of Incontinence Questionnaire (ICIQ) at baseline, 2‐year follow‐up, and 5‐year follow‐up. Four hundred and eighty‐eight men without neurological diseases or prostate cancer during follow‐up, or history of urological treatment at baseline were included in the analysis. Urgency incontinence was defined as leakage of urine occurring more than weekly in the above‐defined population. OAB was defined as either urgency or urgency incontinence according to 2002 International Continence Society consensus.

Results

Of the men with OAB at baseline, 29% received treatment for OAB or benign prostatic enlargement over 5 years. Of the remaining men, 33% had sustained remission at 2‐year and 5‐year follow‐ups without treatment. Of the men with OAB at 2‐year follow‐up, remission rate at 5‐year follow‐up was 53% in men without OAB at baseline and 27% in men with OAB at baseline (P = 0.23). No statistically significant difference was found in baseline characteristics between men with sustained remission and men with persistent symptoms.

Conclusions

One in three older men with non‐neurogenic OAB had sustained remission of symptoms without medical or surgical interventions. No significant predictor of sustained remission was identified. Neurourol. Urodynam. 36:443–448, 2017. © 2016 Wiley Periodicals, Inc.
Retrospective clinic and urodynamic study in the neurogenic bladder dysfunction caused by human T cell lymphotrophic virus type 1 associated myelopathy/tropical spastic paraparesis (HAM/TSP)
Authors: Troisgros Odile , Barnay Jose‐Luis , Darbon‐Naghibzadeh Farideh , Olive Pascale , René‐Corail Patrick
Published: January 2016

Introduction

HTLV‐I associated tropical spastic paraparesis (TSP) and HTLV‐I associated myelopathy (HAM) is an endemic disease in Caribbean Island. Bladder‐sphincter dysfunctions are almost present. The objectives of the study are to describe clinic and urodynamic characteristics of voiding disorders in Martiniquan population, evaluate if there is a relationship between motor and urinary handicap, and evaluate prognosis factors of urologic complications.

Methods

Retrospective study of 60 patients suffering from HAM/TSP. Clinical, urodynamic datas, scale of urinary and motor handicap (Urinary Symptom Profile [USP] questionnaire and Osame Score) were collected.

Results

Storage symptoms were the most frequent (75%) whatever type of detrusor activity. Detrusor overactivity was the most frequent disorder (68.3%). Bladder compliance was normal in half percent of the cases. Urethral activity was increased in 47% of the cases. Detrusor sphincter dysynergia was found in 78% of the cases, post‐void residual in 58% of cases. Sixty five percent of the patients present at least one urologic complication (morphologic and/or infectious) but there was no correlation with motor enablement (P = 0.3097), neither urodynamic study (P = 0.432 for detrusor overactivity, P = 0.107 for detrusor underactivity, P = 0.058 for high urethral activity, P = 0.893 for detrusor sphincter dysynergia, P = 0.850 for post‐void residual volume), neither with evolution duration of HAM/TSP (P = 0.348). USP score was not in correlation with Osame score (P = 0.07).

Conclusion

Urologic symptoms are not always in relationship with urodynamic study: a systematic urodynamic study is necessary to evaluate HAM/TSP neurogenic bladder. No clinic or urodynamic criterias are predictive of urologic complications. These patients need a close follow up. Neurourol. Urodynam. 36:449–452, 2017. © 2016 Wiley Periodicals, Inc.
Velocity‐based formulations for standard and quasi‐incompressible hypoelastic‐plastic solids
Authors: Franci Alessandro , Oñate Eugenio , Carbonell Josep Maria
Published: January 2016

We present three velocity‐based updated Lagrangian formulations for standard and quasi‐incompressible hypoelastic‐plastic solids. Three low‐order finite elements are derived and tested for non‐linear solid mechanics problems. The so‐called V‐element is based on a standard velocity approach, while a mixed velocity–pressure formulation is used for the VP and the VPS elements. The two‐field problem is solved via a two‐step Gauss–Seidel partitioned iterative scheme. First, the momentum equations are solved in terms of velocity increments, as for the V‐element. Then, the constitutive relation for the pressure is solved using the updated velocities obtained at the previous step. For the VPS‐element, the formulation is stabilized using the finite calculus method in order to solve problems involving quasi‐incompressible materials. All the solid elements are validated by solving two‐dimensional and three‐dimensional benchmark problems in statics as in dynamics. Copyright © 2016 John Wiley & Sons, Ltd.
Does worksite social capital enhance retention into a worksite weight‐loss programme?
Authors: Hill J. L. , Wilson K. , Harden S. , Almeida F. , Linnan L. , Estabrooks P. A.
Published: January 2016

Objective

To determine if worksite social capital predicted retention in a worksite‐based weight‐loss programme using structural equation modelling. A secondary aim was to determine if worksite social capital was related to changes in weight at 6 months.

Methods

Overweight or obese employees from 28 worksites enrolled in a larger 12‐month worksite weight‐loss trial. Workplace social capital was assessed using an eight‐item scale specific to the workplace. Weight was measured using a HealthSpottm, and change in weight was computed from weigh‐ins at baseline and 6 months and reported as pounds (lbs) lost. Retention was defined as those employees who completed a weigh‐in at 6 months.

Results

Across the trial, N = 1,790; age = 46.6 ± 11; 73% women; 73% White overweight or obese employees participated. The odds of participant attrition were 1.12 times greater with each unit decrease in social capital score at baseline (p < 0.05), and while the model testing the direct effect of social capital at baseline on weight loss at 6 months demonstrated acceptable fit, social capital was not a significant predictor of weight loss (p > 0.05).

Conclusions

Increased worksite social capital was predictive of retention in a worksite weight‐loss programme. To maximize return on investments for employee wellness and weight‐loss programmes, employers may benefit from understanding the facets of the ‘social’ environment such as social capital that may increase the likelihood of sustained participation.
Correlation of spatially resolved photoluminescence and viscoelastic mechanical properties of encapsulating EVA in differently aged PV modules
Authors: Schlothauer Jan C. , Grabmayer Klemens , Wallner Gernot M. , Röder Beate
Published: January 2016

The photoluminescence of ethylene vinyl acetate (EVA) in aged photovoltaic modules shows specific spatial patterns on the scale of the cells in the module that depend on the aging conditions. It is the aim of this work to investigate the correlation of these photoluminescence patterns to the viscoelastic mechanical properties of the encapsulating EVA.

For this, the degradation under various conditions of two specimen sets of polycrystalline silicon photovoltaic mini‐modules, comprising EVA as encapsulating polymer, is investigated using spatially resolved, ultraviolet‐excited photoluminescence. Samples of the encapsulation EVA are systematically extracted from the modules for spatially resolved dynamic mechanical characterization.

A correlation between the spatial distribution of the photoluminescence intensity and the values of storage modulus and loss factor of the EVA is found. An increase in the values for storage modulus and a decrease of the loss factor of the EVA from the edge of the cell towards the center are observed for all samples. We conclude that diffusion‐limited oxidation must be considered for aging studies of the encapsulation EVA and that photoluminescence detection can reveal the scale on which such diffusion processes occur. Copyright © 2016 John Wiley & Sons, Ltd.
Long‐term impact of temporary and persistent personality disorder on anxiety and depressive disorders
Authors: Tyrer Peter , Tyrer Helen , Yang Min , Guo Boliang
Published: January 2016

Background

It is of interest to know if temporary and persistent personality disorders are associated with different outcomes.

Method

A cohort of 210 people with anxiety and depressive disorders was followed up on nine occasions over 12 years. During this study, personality status was assessed at baseline and after 2 years using two methods, one linked to the new International Classification of Diseases 11th Revision (ICD‐11) severity codes. The impact on the symptomatic outcome and social function of temporary (i.e. personality disorder on one occasion only) and persistent personality disorder (personality disorder present on both occasions) was compared.

Results

Of the 162 patients studied we identified four groups (no personality disorder at any time (n = 46), two with temporary personality disorder (baseline only (n = 33) and 2 years only (n = 28), and persistent personality disorder (n = 55). Those with persistent personality disorder had significantly worse outcomes than other groups for self‐rated anxiety symptoms (p = 0.02) and overall social function (p < 0.001), 81% had a current DSM diagnosis at 12 years compared with 52–65% in the other groups (p < 0.03). Significantly, more patients with ICD‐11 moderate or severe personality disorder at baseline had persistent personality disorder than had temporary disorders (p = 0.017).

Conclusion

Persistent personality disorder is associated with more severe personality dysfunction and has a negative impact on the outcome of common mental disorder and particularly on long‐term social functioning. Copyright © 2016 John Wiley & Sons, Ltd.
Tuning the adsorption and fluorescence properties of aminal‐linked porous organic polymers through N‐heterocyclic group decoration
Authors: Weng Jun‐Ying , Xu Yue‐Ling , Song Wei‐Chao , Zhang Ying‐Hui
Published: January 2016

Aiming at tuning the adsorption and fluorescence properties of targeted porous organic polymer, four new aminal‐linked porous organic polymers (NAPOPs) were synthesized through the reaction of 1,4‐Bis(4,6‐diamino‐s‐triazin‐2‐yl) benzene (BATB) with four kinds of aldehydes substituted with different N‐heterocyclic groups. Among the polymers, NAPOP‐3 decorated with 5‐phenyl‐tetrazole group shows the largest CO2 adsorption capacity (2.52 mmol g−1 at 273 K and 100 kPa) because of its relative large surface area, while NAPOP‐1 decorated with piperazine groups shows relative large CO2/N2 adsorption selectivity (77 at 273 K and 100 kPa), attributable to its large CO2 adsorption heats and cabined pore (<4 Å). Meanwhile, NAPOP‐1 and −3 exhibit high adsorption rate toward iodine with a high capacity (>240 wt %). In addition, different luminescence emissions were also observed for NAPOPs, indicating different intramolecular charger transfer occurred inside polymer networks. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 1724–1730
How mutational epistasis impairs predictability in protein evolution and design
Authors: Miton Charlotte M. , Tokuriki Nobuhiko
Published: January 2016

There has been much debate about the extent to which mutational epistasis, that is, the dependence of the outcome of a mutation on the genetic background, constrains evolutionary trajectories. The degree of unpredictability introduced by epistasis, due to the non‐additivity of functional effects, strongly hinders the strategies developed in protein design and engineering. While many studies have addressed this issue through systematic characterization of evolutionary trajectories within individual enzymes, the field lacks a consensus view on this matter. In this work, we performed a comprehensive analysis of epistasis by analyzing the mutational effects from nine adaptive trajectories toward new enzymatic functions. We quantified epistasis by comparing the effect of mutations occurring between two genetic backgrounds: the starting enzyme (for example, wild type) and the intermediate variant on which the mutation occurred during the trajectory. We found that most trajectories exhibit positive epistasis, in which the mutational effect is more beneficial when it occurs later in the evolutionary trajectory. Approximately half (49%) of functional mutations were neutral or negative on the wild‐type background, but became beneficial at a later stage in the trajectory, indicating that these functional mutations were not predictable from the initial starting point. While some cases of strong epistasis were associated with direct interaction between residues, many others were caused by long‐range indirect interactions between mutations. Our work highlights the prevalence of epistasis in enzyme adaptive evolution, in particular positive epistasis, and suggests the necessity of incorporating mutational epistasis in protein engineering and design to create highly efficient catalysts.
Using a second‐order differential model to fit data without baselines in protein isothermal chemical denaturation
Authors: Tang Chuanning , Lew Scott , He Dacheng
Published: January 2016

In vitro protein stability studies are commonly conducted via thermal or chemical denaturation/renaturation of protein. Conventional data analyses on the protein unfolding/(re)folding require well‐defined pre‐ and post‐transition baselines to evaluate Gibbs free‐energy change associated with the protein unfolding/(re)folding. This evaluation becomes problematic when there is insufficient data for determining the pre‐ or post‐transition baselines. In this study, fitting on such partial data obtained in protein chemical denaturation is established by introducing second‐order differential (SOD) analysis to overcome the limitations that the conventional fitting method has. By reducing numbers of the baseline‐related fitting parameters, the SOD analysis can successfully fit incomplete chemical denaturation data sets with high agreement to the conventional evaluation on the equivalent completed data, where the conventional fitting fails in analyzing them. This SOD fitting for the abbreviated isothermal chemical denaturation further fulfills data analysis methods on the insufficient data sets conducted in the two prevalent protein stability studies.
Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIβ with Rab11
Authors: Fowler Melissa L. , McPhail Jacob A. , Jenkins Meredith L. , Masson Glenn R. , Rutaganira Florentine U. , Shokat Kevan M. , Williams Roger L. , Burke John E.
Published: January 2016

The ability of proteins to bind and interact with protein partners plays fundamental roles in many cellular contexts. X‐ray crystallography has been a powerful approach to understand protein‐protein interactions; however, a challenge in the crystallization of proteins and their complexes is the presence of intrinsically disordered regions. In this article, we describe an application of hydrogen deuterium exchange mass spectrometry (HDX‐MS) to identify dynamic regions within type III phosphatidylinositol 4 kinase beta (PI4KIIIβ) in complex with the GTPase Rab11. This information was then used to design deletions that allowed for the production of diffraction quality crystals. Importantly, we also used HDX‐MS to verify that the new construct was properly folded, consistent with it being catalytically and functionally active. Structures of PI4KIIIβ in an Apo state and bound to the potent inhibitor BQR695 in complex with both GTPγS and GDP loaded Rab11 were determined. This hybrid HDX‐MS/crystallographic strategy revealed novel aspects of the PI4KIIIβ‐Rab11 complex, as well as the molecular mechanism of potency of a PI4K specific inhibitor (BQR695). This approach is widely applicable to protein‐protein complexes, and is an excellent strategy to optimize constructs for high‐resolution structural approaches.
COMSAT: Residue contact prediction of transmembrane proteins based on support vector machines and mixed integer linear programming
Authors: Zhang Huiling , Huang Qingsheng , Bei Zhendong , Wei Yanjie , Floudas Christodoulos A.
Published: January 2016

In this article, we present COMSAT, a hybrid framework for residue contact prediction of transmembrane (TM) proteins, integrating a support vector machine (SVM) method and a mixed integer linear programming (MILP) method. COMSAT consists of two modules: COMSAT_SVM which is trained mainly on position–specific scoring matrix features, and COMSAT_MILP which is an ab initio method based on optimization models. Contacts predicted by the SVM model are ranked by SVM confidence scores, and a threshold is trained to improve the reliability of the predicted contacts. For TM proteins with no contacts above the threshold, COMSAT_MILP is used. The proposed hybrid contact prediction scheme was tested on two independent TM protein sets based on the contact definition of 14 Å between Cα‐Cα atoms. First, using a rigorous leave‐one‐protein‐out cross validation on the training set of 90 TM proteins, an accuracy of 66.8%, a coverage of 12.3%, a specificity of 99.3% and a Matthews' correlation coefficient (MCC) of 0.184 were obtained for residue pairs that are at least six amino acids apart. Second, when tested on a test set of 87 TM proteins, the proposed method showed a prediction accuracy of 64.5%, a coverage of 5.3%, a specificity of 99.4% and a MCC of 0.106. COMSAT shows satisfactory results when compared with 12 other state‐of‐the‐art predictors, and is more robust in terms of prediction accuracy as the length and complexity of TM protein increase. COMSAT is freely accessible at http://hpcc.siat.ac.cn/COMSAT/. Proteins 2016; 84:332–348. © 2016 Wiley Periodicals, Inc.
Identification of putative unfolding intermediates of the mutant His‐107‐tyr of human carbonic anhydrase II in a multidimensional property space
Authors: Halder Puspita , Taraphder Srabani
Published: January 2016

In this article, we develop an extensive search procedure of the multi‐dimensional folding energy landscape of a protein. Our aim is to identify different classes of structures that have different aggregation propensities and catalytic activity. Following earlier studies by Daggett et al. [Jong, D. D.; Riley, R.: Alonso, D.O.: Dagett, V. J. Mol. Biol. 2002, 319, 229], a series of high temperature all‐atom classical molecular simulation studies has been carried out to derive a multi‐dimensional property space. Dynamical changes in these properties are then monitored by projecting them along a one‐dimensional reaction coordinate, dmean. We have focused on the application of this method to partition a wide array of conformations of wild type human carbonic anhydrase II (HCA II) and its unstable mutant His‐107‐Tyr along dmean by sampling a 35‐dimensional property space. The resultant partitioning not only reveals the distribution of conformations corresponding to stable structures of HCA II and its mutant, but also allows the monitoring of several partially unfolded and less stable conformations of the mutant. We have investigated the population of these conformations at different stages of unfolding and collected separate sets of structures that are widely separated in the property space. The dynamical diversity of these sets are examined in terms of the loading of their respective first principal component. The partially unfolded structures thus collected are qualitatively mapped on to the experimentally postulated light molten globule (MGL) and molten globule (MG) intermediates with distinct aggregation propensities and catalytic activities. Proteins 2016; 84:726–743. © 2016 Wiley Periodicals, Inc.
Conformation of membrane‐bound proteins revealed by vacuum‐ultraviolet circular‐dichroism and linear‐dichroism spectroscopy
Authors: Matsuo Koichi , Maki Yasuyuki , Namatame Hirofumi , Taniguchi Masaki , Gekko Kunihiko
Published: January 2016

Knowledge of the conformations of a water‐soluble protein bound to a membrane is important for understanding the membrane‐interaction mechanisms and the membrane‐mediated functions of the protein. In this study we applied vacuum‐ultraviolet circular‐dichroism (VUVCD) and linear‐dichroism (LD) spectroscopy to analyze the conformations of α‐lactalbumin (LA), thioredoxin (Trx), and β‐lactoglobulin (LG) bound to phosphatidylglycerol liposomes. The VUVCD analysis coupled with a neural‐network analysis showed that these three proteins have characteristic helix‐rich conformations involving several helical segments, of which two amphiphilic or hydrophobic segments take part in interactions with the liposome. The LD analysis predicted the average orientations of these helix segments on the liposome: two amphiphilic helices parallel to the liposome surface for LA, two hydrophobic helices perpendicular to the liposome surface for Trx, and a hydrophobic helix perpendicular to and an amphiphilic helix parallel to the liposome surface for LG. This sequence‐level information about the secondary structures and orientations was used to formulate interaction models of the three proteins at the membrane surface. This study demonstrates the validity of a combination of VUVCD and LD spectroscopy in conformational analyses of membrane‐binding proteins, which are difficult targets for X‐ray crystallography and nuclear magnetic resonance spectroscopy. Proteins 2016; 84:349–359. © 2016 Wiley Periodicals, Inc.
Crystal structure of archaeal ketopantoate reductase complexed with coenzyme a and 2‐oxopantoate provides structural insights into feedback regulation
Authors: Aikawa Yoshiki , Nishitani Yuichi , Tomita Hiroya , Atomi Haruyuki , Miki Kunio
Published: January 2016

Coenzyme A (CoA) plays essential roles in a variety of metabolic pathways in all three domains of life. The biosynthesis pathway of CoA is strictly regulated by feedback inhibition. In bacteria and eukaryotes, pantothenate kinase is the target of feedback inhibition by CoA. Recent biochemical studies have identified ketopantoate reductase (KPR), which catalyzes the NAD(P)H‐dependent reduction of 2‐oxopantoate to pantoate, as a target of the feedback inhibition by CoA in archaea. However, the mechanism for recognition of CoA by KPR is still unknown. Here we report the crystal structure of KPR from Thermococcus kodakarensis in complex with CoA and 2‐oxopantoate. CoA occupies the binding site of NAD(P)H, explaining the competitive inhibition by CoA. Our structure reveals a disulfide bond between CoA and Cys84 that indicates an irreversible inhibition upon binding of CoA. The structure also suggests the cooperative binding of CoA and 2‐oxopantoate that triggers a conformational closure and seems to facilitate the disulfide bond formation. Our findings provide novel insights into the mechanism that regulates biosynthesis of CoA in archaea. Proteins 2016; 84:374–382. © 2016 Wiley Periodicals, Inc.
Foliar application of microdoses of sucrose to reduce codling moth Cydia pomonella L. (Lepidoptera: Tortricidae) damage to apple trees
Authors: Arnault Ingrid , Lombarkia Nadia , Joy‐Ondet Sophie , Romet Lionel , Brahim Imene , Meradi Rahma , Nasri Ardjouna , Auger Jacques , Derridj Sylvie
Published: January 2016

BACKGROUND

The effects of foliar applications of microdoses of sucrose to reduce the damage by the codling moth have been reported from nine trials carried in France and Algeria from 2009 to 2014. The activity of sucrose alone was assessed by comparison with an untreated control and some treatments with the Cydia pomonella granulovirus or a chemical insecticide. The addition of sucrose to these different treatments was also investigated.

RESULTS

The application of sucrose at 0.01% reduced the means of infested fruits with a value of Abbott's efficacy of 41.0 ± 10.0%. This involved the induction of resistance by antixenosis to insect egg laying. Indeed, it seems that acceptance of egg laying on leaves treated with sucrose was reduced. The addition of sucrose to thiacloprid improved its efficacy (59.5% ± 12.8) by 18.4%. However, the sucrose had no added value when associated with C. pomonella granulovirus treatments.

CONCLUSION

Foliar applications of microdoses of sucrose every 20 days in commercial orchards can partially protect against the codling moth. Its addition to thiacloprid increases the efficacy in integrated control strategies, contrary to C. pomonella granulovirus treatments. This work opens a route for the development of new biocontrol strategies. © 2016 Society of Chemical Industry
Confidence intervals for the symmetry point: an optimal cutpoint in continuous diagnostic tests
Authors: López‐Ratón Mónica , Cadarso‐Suárez Carmen , Molanes‐López Elisa M. , Letón Emilio
Published: January 2016

Continuous diagnostic tests are often used for discriminating between healthy and diseased populations. For this reason, it is useful to select an appropriate discrimination threshold. There are several optimality criteria: the North‐West corner, the Youden index, the concordance probability and the symmetry point, among others. In this paper, we focus on the symmetry point that maximizes simultaneously the two types of correct classifications. We construct confidence intervals for this optimal cutpoint and its associated specificity and sensitivity indexes using two approaches: one based on the generalized pivotal quantity and the other on empirical likelihood. We perform a simulation study to check the practical behaviour of both methods and illustrate their use by means of three real biomedical datasets on melanoma, prostate cancer and coronary artery disease. Copyright © 2016 John Wiley & Sons, Ltd.
Impact of targeted observations on HIRLAM forecasts during HyMeX‐SOP1
Authors: Campins Joan , Navascués Beatriz
Published: January 2016

An adaptive observing system with terrestrial and space‐based components has been explored, with the aim of improving numerical weather prediction skill in the Mediterranean. Four Observing System Experiments based on the HIRLAM system have been conducted to test the influence of targeted observations on short‐term forecasts of high‐impact weather events over the first Special Observation Period of the HyMeX international project. Extra radiosoundings and enhanced Advanced TIROS Operational Vertical Sounder (ATOVS) satellite observations are assimilated as targeted observations, and have been added to the baseline first separately and then jointly. In general, targeted observations have a positive but small impact on the short‐term forecasts, noticeably at 700 to 500 hPa in all parameters and precipitation. Targeted radiosoundings produce a clear overall improvement of HIRLAM forecasts. Data targeting based only on satellite observations has a generally positive impact on precipitation, and in short‐term forecasts of the rest of the parameters. The assimilation of both types of extra observations produces the highest and most statistically significant improvements. The magnitude of the impact on the forecasts depends on the weather regime that determines the location of sensitive areas. According to the diagnostics obtained from the data assimilation cycle, the targeted observations had a still larger positive influence on the subsequent analyses. Extra radiosoundings and additional satellite radiances clearly improve the first‐guess quality over land and sea sensitive areas respectively.
Algorithm for generating cloud‐mask from multi‐channel satellite data
Authors: Ojha Satya P. , Singh Randhir , Shukla Munn V.
Published: January 2016

This article presents an algorithm for generating cloud‐mask, over the ocean, from multi‐channel satellite data. The algorithm is based on the assumption that, at any given instant of time, the observed radiances are a mixture of many Gaussians where each Gaussian mixture component is representative of a scene (clear or cloudy). The problem is attempted as one of the unsupervised clustering. The clusters in the data are separated using a Gaussian mixture model. The proposed algorithm is applied on INSAT‐3D imager data and its performance is assessed by comparing the cloud‐mask thus generated against the Moderate Resolution Imaging Spectroradiometer (MODIS) cloud‐mask for forty selected days in the year 2014. The skill of the algorithm developed in this study is about 20% higher than the algorithm currently operational for generating the INSAT‐3D cloud‐mask. Due to the fact that currently geophysical parameter retrieval (e.g. sea‐surface temperature) and data assimilation are performed in clear‐sky regions, the developed algorithm will have large implications in retrieval and data assimilation studies.
An invasive‐native mammalian species replacement process captured by camera trap survey random encounter models
Authors: Caravaggi Anthony , Zaccaroni Marco , Riga Francesco , Schai‐Braun Stéphanie C. , Dick Jaimie T.A. , Montgomery W. Ian , Reid Neil
Published: January 2016

Camera traps are used to estimate densities or abundances using capture‐recapture and, more recently, random encounter models (REMs). We deploy REMs to describe an invasive‐native species replacement process, and to demonstrate their wider application beyond abundance estimation. The Irish hare Lepus timidus hibernicus is a high priority endemic of conservation concern. It is threatened by an expanding population of nonnative, European hares L. europaeus, an invasive species of global importance. Camera traps were deployed in thirteen 1 km squares, wherein the ratio of invader to native densities were corroborated by night‐driven line transect distance sampling throughout the study area of 1652 km2. Spatial patterns of invasive and native densities between the invader's core and peripheral ranges, and native allopatry, were comparable between methods. Native densities in the peripheral range were comparable to those in native allopatry using REM, or marginally depressed using Distance Sampling. Numbers of the invader were substantially higher than the native in the core range, irrespective of method, with a 5:1 invader‐to‐native ratio indicating species replacement. We also describe a post hoc optimization protocol for REM which will inform subsequent (re‐)surveys, allowing survey effort (camera hours) to be reduced by up to 57% without compromising the width of confidence intervals associated with density estimates. This approach will form the basis of a more cost‐effective means of surveillance and monitoring for both the endemic and invasive species. The European hare undoubtedly represents a significant threat to the endemic Irish hare.