bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensional mapping of the orientation of collagen corneal lamellae in healthy and keratoconic human corneas using SHG microscopy
Authors: Mercatelli Raffaella , Ratto Fulvio , Rossi Francesca , Tatini Francesca , Menabuoni Luca , Malandrini Alex , Nicoletti Riccardo , Pini Roberto , Pavone Francesco Saverio , Cicchi Riccardo
Published: August 2016

Keratoconus is an eye disorder that causes the cornea to take an abnormal conical shape, thus impairing its refractive functions and causing blindness. The late diagnosis of keratoconus is among the principal reasons for corneal surgical transplantation. This pathology is characterized by a reduced corneal stiffness in the region immediately below Bowman's membrane, probably due to a different lamellar organization, as suggested by previous studies. Here, the lamellar organization in this corneal region is characterized in three dimensions by means of second‐harmonic generation (SHG) microscopy. In particular, a method based on a three‐dimensional correlation analysis allows to probe the orientation of sutural lamellae close to the Bowman's membrane, finding statistical differences between healthy and keratoconic samples. This method is demonstrated also in combination with an epi‐detection scheme, paving the way for a potential clinical ophthalmic application of SHG microscopy for the early diagnosis of keratoconus.

SHG image acquired with sagittal optical sectioning (A) of a healthy cornea and (B) of a keratoconic cornea. Scale bars: 30 μm.

magnified image

SHG image acquired with sagittal optical sectioning (A) of a healthy cornea and (B) of a keratoconic cornea. Scale bars: 30 μm.
Synthesis, Molecular Docking and Potential Antioxidant Activity of Di/Trisubstituted Pyridazinone Derivatives
Authors: Khokra Sukhbir Lal , Khan Shah Alam , Thakur Pramila , Chowdhary Deepika , Ahmad Aftab , Husain Asif
Published: August 2016

A number of pyridazinone derivatives bearing substituted benzylidene and heterocyclic/aromatic rings at 4th and 6th positions, respectively were synthesized in good to moderate yields and screened for antioxidant activity. Antioxidant activity of pyridazinone derivatives was evaluated by using several in vitro radical scavenging methods such as 1,1‐diphenylpicrylhydrazyl (DPPH), hydrogen peroxide (H2O2), nitric oxide (NO), reducing power, and metal chelating assay etc. Molegro virtual docker software was used to study the binding affinity of the title compounds with the xanthine oxidoreductase enzyme. Amongst the tested compounds, 5a, 5d, 5g & 5j were found to exhibit excellent antioxidant activity at par with the positive control, ascorbic acid. The molecular docking studies of these compounds demonstrated a good selectivity profile with xanthine oxidoreductase receptors. A preliminary study of the structural‐activity relationship showed that the presence of electron withdrawing group and heterocyclic ring on pyridazinone nucleus are associated with the best potency and selectivity profile. It could be proposed that xanthine oxidoreductase receptor may be involved in observed antioxidant activity of pyridazinone derivatives bearing aromatic ring and benzylidene substituents and thus the synthesized compounds are worthy of further exploration.
Peripartum Depression, Traditional Culture, and Israeli Society
Authors: Dekel Sharon , Stanger Varda , Georgakopoulos Emily R , Stuebe Caren M , Dishy Gabriella A
Published: August 2016

Although it is known that culture affects psychopathology, the nature of the relationship between culture and peripartum depression (PPD) is not fully understood. Here we report on 2 cases of Israeli women who are affiliated with traditional cultural groups that emphasize reproduction but developed PPD after childbirth. The first woman is an ultra‐Orthodox Israeli Jew and the second is an Israeli Arab. The 2 cases illustrate the effect of cultural beliefs and rituals on the conceptualization, treatment, and trajectory of PPD. The cases suggest a complex relationship between traditional cultures and PPD, including the possibility that cultural factors may have both adaptive and maladaptive consequences. Future qualitative and quantitative studies are needed to further clarify this relationship.
Stable isotope composition of cocoa beans of different geographical origin
Authors: Perini Matteo , Bontempo Luana , Ziller Luca , Barbero Alice , Caligiani Augusta , Camin Federica
Published: August 2016

The isotopic profile (δ13C, δ15N, δ18O, δ2H, δ34S) was used to characterise a wide selection of cocoa beans from different renowned production areas (Africa, Asia, Central and South America). The factors most influencing the isotopic signatures of cocoa beans were climate and altitude for δ13C and the isotopic composition of precipitation water for δ18O and δ2H, whereas δ15N and δ34S were primarily affected by geology and fertilisation practises. Multi‐isotopic analysis was shown to be sufficiently effective in determining the geographical origin of cocoa beans, and combining it with Canonical Discriminant Analysis led to more than 80% of samples being correctly reclassified. Copyright © 2016 John Wiley & Sons, Ltd.
The Beginnings of Agility at Brioche Pasquier
Authors: Worley Christopher G. , Zardet Véronique , Bonnet Marc , Savall Amandine
Published: August 2016

Seeking to grow its business while managing the risks of expansion, preserving a family business culture, and ensuring effective succession planning, the French baking firm of Brioche Pasquier Group in 1984 turned to consultants from the Institute for Socio‐Economic Organization Research for assistance. Together, they implemented the socioeconomic approach to management (SEAM) to strengthen the firm's core planning, operational, and human resource structures; increase efficiency and convert hidden costs into value‐added activities; reorganize production processes; streamline delivery; better connect with customers; and improve teamwork. Over time, the SEAM methodology supported the emergence of an agile organization. The practices put into place have helped the company adapt to the challenges in its industry for more than three decades. © 2016 Wiley Periodicals, Inc.
Putting Vision Into Action Through a Triple Bottom Line Approach at Zensar Technologies
Authors: Natarajan Ganesh
Published: August 2016

When the managers of Zensar Technologies in western India set out to establish their firm as a leader in the competitive global business process outsourcing market, they implemented Vision Communities to improve organizational focus, flexibility, and performance through enhanced employee participation and societal involvement. The company's triple bottom line approach to profits, people, and the planet is rooted in a “philosophy of love” value system that motivates associates at all levels and fosters an engaging work environment characterized by mutual respect, transparency, innovation, passion for excellence, corporate social responsibility, and fun. © 2016 Wiley Periodicals, Inc.
Theoretical study of normal Raman spectra and SERS of benzyl chloride and benzyl radical on silver electrodes
Authors: Chen Yan‐Li , Panneerselvam Rajapandiyan , Wu De‐Yin , Tian Zhong‐Qun
Published: August 2016

Electrochemical surface‐enhanced Raman spectroscopy has been used to characterize adsorbed species widely but rarely to reaction intermediates on electrodes. In previous studies, the observed surface‐enhanced Raman spectroscopy signals were proposed from benzyl species due to the electrochemical reduction of benzyl chloride on silver electrode surfaces. In this work, we reinvestigated the vibrational assignments of benzyl chloride and benzyl radical as the reaction intermediate. On the basis of density functional theory calculations and normal mode analysis, our systematic results provide more reasonable new assignments for both surface species. Further, we investigated adsorption configurations, binding energies, and vibrational frequency shifts of benzyl radical interacting with silver. Our calculated results show that the wagging vibration displays significant vibrational frequency shift, strong coupling with some intramolecular modes in the phenyl ring, and significant changes in intensity of Raman signals. The study also provides absolute Raman intensity in benzyl halides and discusses the enhancement effect mainly due to the binding interaction with respect to free benzyl radical. Copyright © 2016 John Wiley & Sons, Ltd.
A critical analysis of melanoma malpractice litigation: Should we biopsy everything?
Authors: Rayess Hani M. , Gupta Amar , Svider Peter F. , Raza S. Naweed , Shkoukani Mahdi , Zuliani Giancarlo F. , Carron Michael A.
Published: August 2016

Objectives/Hypothesis

The aim of this study was to evaluate factors raised in malpractice litigation related to the diagnosis and management of melanoma and to further assess issues impacting outcome.

Study Design

Retrospective chart review.

Methods

The Westlaw legal database was searched for malpractice litigation resolved over the last 20 years relating to melanoma. Cases were evaluated for allegations, defendant specialty, outcome, and other issues raised.

Results

Of the 80 cases evaluated, 49% were resolved in the defendants' favor. In greater than 80% of cases, there was alleged misdiagnosis. In 35% of cases, the patient had expired secondary to melanoma at the time of litigation. There was no statistical difference in payments upon comparison of cases with and without mortality. A greater proportion of cases with dermatologists and pathologists as defendants involved alleged misdiagnosis. The most common locations for melanoma were the extremities and the head‐and‐neck region, at 32.5% and 22.5%, respectively. Location did not significantly impact the outcome of cases.

Conclusion

Malpractice litigation relating to melanoma involves numerous physicians, including dermatologists, pathologists, and otolaryngologists. Alleged misdiagnosis of a pigmented lesion was the most common cause of litigation and involved physicians from numerous specialties. Patients who were misdiagnosed had a significantly higher likelihood of having active disease at the time of litigation. Ultimately improved methods of detecting concerning pigmented lesions need to be developed. Factors such as death and poor cosmetic outcome did not significantly impact litigation outcome.

Level of Evidence

NA Laryngoscope, 127:134–139, 2017
Blunt cerebrovascular injury following craniomaxillofacial fractures: A systematic review
Authors: Kelts Gregory , Maturo Stephen , Couch Marion Everett , Schmalbach Cecelia E.
Published: August 2016

Objectives

Blunt cerebrovascular injury (BCVI) is a known sequela of high‐energy craniomaxillofacial (CMF) trauma and can result in stroke or death. The objective of this systematic review is to 1) identify CMF trauma patients who may benefit from BCVI screening and 2) describe the optimal diagnostic and treatment modalities.

Study Design

Systematic review of the literature (1946–2013).

Methods

An a priori study protocol was created using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis. The authors conducted a search of Ovid/Medline, PubMed, and Cochrane databases for articles related to BCVI and CMF fractures. All abstracts were reviewed, and data was extracted to determine the incidence of BCVI in the setting of CMF trauma. Individual fracture patterns were analyzed using descriptive statistics.

Results

Twenty‐one studies met inclusion criteria. The overall incidence of CMF fracture‐associated BCVI was 0.45%. The majority of patients (86.6%) sustained BCVI in the setting of high‐energy trauma. The distribution of CMF fractures among BCVI patients was the mandible (12.5%), followed by the maxilla (11.8%). Computed tomographic angiography (CTA) was the most common diagnostic modality. A total of 63.1% of patients with BCVI were managed medically. The mortality among CMF patients with BCVI was 23.9%, and stroke rate was 47.1%.

Conclusion

Blunt cerebrovascular injury is a rare but devastating complication of blunt trauma. The recommended screening modality is CTA, and the most common treatment is antiplatelet/anticoagulant medication. Mandibular and LeFort fractures were the most common isolated CMF injury associated with BCVI, highlighting the need for prospective trials to expand current screening criteria.

Level of Evidence

N/A. Laryngoscope, 127:79–86, 2017
Polarization control over electric and magnetic dipole resonances of dielectric nanoparticles on metallic films
Authors: Sinev Ivan , Iorsh Ivan , Bogdanov Andrey , Permyakov Dmitry , Komissarenko Filipp , Mukhin Ivan , Samusev Anton , Valuckas Vytautas , Kuznetsov Arseniy I. , Luk'yanchuk Boris S. , Miroshnichenko Andrey E. , Kivshar Yuri S.
Published: August 2016

We reveal unusually strong polarization sensitivity of electric and magnetic dipole resonances of high‐index dielectric nanoparticles placed on a metallic film. By employing dark‐field spectroscopy, we observe the polarization‐controlled transformation from high‐Q magnetic‐dipole scattering to broadband suppression of scattering associated with the electric dipole mode, and show numerically that it is accompanied by a strong enhancement of the respective fields by the nanoparticle. Our experimental data for silicon nanospheres are in an excellent agreement with both analytical calculations based on Green's function approach and the full‐wave numerical simulations. Our findings further substantiate dielectric nanoparticles as strong candidates for many applications in enhanced sensing, spectroscopy and nonlinear processes at the nanoscale.

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Polymeric Photoinitiators: A New Search toward High Performance Visible Light Photoinitiating Systems
Authors: Zhang Jing , Xiao Pu , Dumur Frédéric , Guo Chang , Hong Wei , Li Yuning , Gigmes Didier , Graff Bernadette , Fouassier Jean‐Pierre , Lalevée Jacques
Published: August 2016

A series of conjugated polymers and oligomers previously used in organic photovoltaics and organic light‐emitting diodes (OLEDs) have been examined for the first time as photoinitiators of polymerization. They address the present and future challenges facing photopolymerization: requirement of high extinction molar coefficients, absorption over the whole visible spectrum, ability to easily withdraw or release electrons. Interestingly, these compounds initiate the cationic polymerization of epoxides or the free radical polymerization of acrylates upon exposure of the photocurable formulations to a LED emitting at 405 nm. Some of them can potentially operate under blue, green, or red laser diodes.

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Thermoreversible Self‐Healing Networks Based on a Tunable Polymethacrylate Crossslinker Having Pendant Maleimide Groups
Authors: Arunbabu Dhamodaran , Noh Seung Man , Nam Joon Hyun , Oh Jung Kwon
Published: August 2016

Self‐healable crosslinked networks able to effectively repair physical damages with no needs of extra healing agents have been developed as effective building blocks in constructing high‐performance industrial and biomedical materials. Here, the development of novel polymer‐based crosslinked materials exhibiting thermally induced self‐healability is reported. The new approach centers on the design and synthesis of polymethacrylates having tunable densities of pendant furan‐protected maleimide groups (PMIMA) as multivalent crosslinkers using a controlled polymerization. Upon the loss of furan protecting groups at elevated temperatures, the PMIMA involves covalent crosslinking with polymethacrylates bearing pendant furan groups in reactive blends. The resulting crosslinked networks exhibit greater thermal stability as well as self‐healability through thermo­reversible Diels‐Alder/Retro Diels‐Alder chemistry, offering versatility in surface‐protective coatings.

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Nontrivial minimal surfaces in a hyperbolic Randers space
Authors: Cui Ningwei , Shen Yi‐Bing
Published: August 2016

The contribution of this paper is two‐fold. The first one is to derive a simple formula of the mean curvature form for a hypersurface in the Randers space with a Killing vector field, by considering the Busemann–Hausdorff measure and Holmes–Thompson measure simultaneously. The second one is to obtain the explicit local expressions of two types of nontrivial rotational BH‐minimal surfaces in a Randers domain of constant flag curvature , which are the first examples of BH‐minimal surfaces in the hyperbolic Randers space.
Simulation of through‐hardening of SAE 52100 steel bearings – Part I: Determination of material properties
Authors: Mustak O. , Evcil E. , Simsir C.
Published: August 2016

A complete material dataset for the simulation of through‐hardening of SAE 52100 (DIN/EN 100Cr6, JIS SUJ2) steel was derived by a combination of experimental and theoretical/computational methods. In the experimental part, alpha/quenching and deformation dilatometry techniques are combined with density measurements, X‐Ray diffraction, optical and scanning electron microscopy to determine temperature and phase dependent transformation kinetics parameters, thermal and transformation strains, flow curves and the transformation plasticity parameter. Thermal properties such as thermal conductivity, specific heat and enthalpy and elastic properties are acquired by thermodynamics based material property calculation method using a commercial software. For most of the material properties, the results were in good agreement with the literature, while the minor discrepancies are discussed considering the raw material, equipment used, testing and evaluation procedure. In Part II of this article, compiled material data is validated successfully in an industrial oil and salt‐bath quenching of bearing races.
Factorization of the transition matrix for the general Jacobi system
Authors: Aktosun Tuncay , Choque‐Rivero Abdon E.
Published: August 2016

The Jacobi system on a full‐line lattice is considered when it contains additional weight factors. A factorization formula is derived expressing the scattering from such a generalized Jacobi system in terms of the scattering from its fragments. This is performed by writing the transition matrix for the generalized Jacobi system as an ordered matrix product of the transition matrices corresponding to its fragments. The resulting factorization formula resembles the factorization formula for the Schrödinger equation on the full line. Copyright © 2016 John Wiley & Sons, Ltd.
Comparison of glycosaminoglycan chemical exchange saturation transfer using Gaussian‐shaped and off‐resonant spin‐lock radiofrequency pulses in intervertebral disks
Authors: Müller‐Lutz Anja , Cronenberg Tom , Schleich Christoph , Wickrath Frithjof , Zaiss Moritz , Boos Johannes , Wittsack Hans‐Jörg
Published: August 2016

Purpose

To investigate, if a train of spin‐lock pulses (chemical exchange saturation transfer with spin‐lock pulses = CESL) improves biochemical glycosaminoglycan imaging compared with conventional chemical exchange saturation transfer with Gaussian‐shaped pulses (CEST) in lumbar intervertebral discs.

Methods

T2, CEST, and CESL imaging was performed in lumbar intervertebral discs of 15 healthy volunteers at 3 Tesla. Mean and standard deviation of the asymmetric magnetization transfer ratio (MTRasym), the asymmetric spin‐lock ratio (SLRasym) and T2 values were calculated for nucleus pulposus (NP) and annulus fibrosus (AF). Wilcoxon test was used to analyze differences between MTRasym and SLRasym. Pearson correlation was used to determine the relationship between MTRasym, SLRasym and T2.

Results

Data showed no significant difference between MTRasym and SLRasym (NP: P = 0.35; AF: P = 0.34). MTRasym and SLRasym values differed significantly between NP and AF (MTRasym: P = 0.014, SLRasym: P = 0.005). T2 values correlated significantly with MTRasym (NP: ρ = 0.76, P < 0.001; AF: ρ = 0.60, P < 0.001) and SLRasym (NP: ρ = 0.73, P < 0.001; AF: ρ = 0.47, P < 0.001).

Conclusion

CESL does not improve the chemical exchange asymmetry effect compared with conventional CEST, but leads to comparable results. Magn Reson Med 78:280–284, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Acid‐Responsive Absorption and Emission of 5‐N‐Arylaminothiazoles: Emission of White Light from a Single Fluorescent Dye and a Lewis Acid
Authors: Yamaguchi Kirara , Murai Toshiaki , Guo Jing‐Dong , Sasamori Takahiro , Tokitoh Norihiro
Published: August 2016

Solutions of 5‐N‐arylaminothiazoles containing pyridyl groups exhibited clear halochromism and halofluorism upon addition of Brønsted and Lewis acids. The addition of triflic acid to solutions of 5‐N‐arylaminothiazoles in Et2O induced bathochromic shifts of the absorption and emission bands. DFT calculations suggested that the spectral changes arise from the protonation of the pyridyl group of the thiazoles in Et2O. Single‐crystal X‐ray diffraction analysis of a thiazole and its protonated form revealed the change of the conformation around the thiazole ring. The emission of white light was accomplished from a single fluorescent dye by adjusting the ratio of dye and B(C6F5)3, whereby the International Commission on Illumination coordinates showed a linear change from blue to orange.
Tensile properties retention of aged carbon‐FRP sheets made of fully and partially bio‐based resins and conventional epoxy
Authors: McSwiggan Ciaran , Fam Amir
Published: August 2016

This article investigates the environmental aging of two types of bio‐resin carbon fiber reinforced polymer (CFRP) through immersion in saltwater at various temperatures, and compares results to conventional epoxy (E)‐CFRP. The two types are: a fully bio‐resin, namely furfural alcohol (FA), derived from corn‐cobs and sugarcane, and the second is a partial bio‐resin, namely epoxidized pine oil blend (EP) extracted from pine tree sap. Control specimens showed that EP resin resulted in similar CFRP strength and modulus to E resin, whereas FA resin resulted in a 9% lower strength and 14% higher modulus. These were shown by the Analysis of Variance (ANOVA) to be statistically insignificant. After 240 days exposure, tensile strength retentions of EP‐CFRP at 23°C, 40°C, and 50°C were 97%, 98%, and 92%, respectively, while those of FA‐CFRP were 83%, 81%, and 82%. For reference, retentions of E‐CFRP were 101%, 90%, and 95%. ANOVA showed that the differences in retentions between EP‐ and E‐CFRP are statistically insignificant at all temperatures, while the differences between FA‐ and E‐CFRP are significant at 23°C and 50°C after 240 days only. Also, the reductions in strength over the 240 days for each resin type are insignificant, except for FA‐CFRP at 50°C. CFRP generally suffered remarkably less deterioration than glass‐FRP at elevated temperatures, for both E and FA resins. POLYM. COMPOS., 39:2081–2092, 2018. © 2016 Society of Plastics Engineers
Patient Variables Associated with Nafcillin Plasma Concentrations and Toxicity
Authors: Benefield Russell J. , Barker Brian C. , Gast Christopher M. , Alexander Donald P.
Published: August 2016

Objectives

Primary objective: To retrospectively review nafcillin plasma concentrations (CNAF) and determine nafcillin clearance (CLNAF) in a diverse sample of patients treated with nafcillin administered as a continuous infusion. Secondary objective: To identify clinical variables associated with CLNAF and nafcillin‐related adverse drug reactions (ADRs).

Methods

Retrospective chart review of patients receiving nafcillin via continuous infusion at University of Utah Health Care from 2006 to 2013 who had at least one steady‐state CNAF measured. CLNAF was determined by dividing the nafcillin rate of infusion by CNAF. Adverse drug reactions (ADRs) were defined using the National Institutes of Health, Division of Microbiology and Infectious Diseases criteria and scored for probability of association with nafcillin by using Naranjo criteria. Multivariate models were constructed to identify independent variables associated with CLNAF and ADRs.

Main results

Seventy‐six CNAF from 54 patients were included. Median CLNAF was 13.9 L/hour (range ≤ 4.2 to 36.9 L/hr). Congestive heart failure (p=0.007), hyperbilirubinemia (p<0.0001), and serum creatinine (p<0.0001) were associated with reduced CLNAF, and Hispanic race (p=0.002) was associated with increased CLNAF by multivariate analysis. Twenty patients (37.0%) experienced an ADR. CNAF were significantly higher between patients that experienced an ADR and those that did not (66.0 vs 25.5 mg/L, p<0.001). Individual ADRs associated with CNAF included hepatotoxicity (62.8 vs 27.0 mg/L, p=0.001), nausea/vomiting (80.0 vs 28.5 mg/L, p=0.01), and diarrhea (66.5 vs 26.5 mg/L, p<0.001). Multivariate analysis identified CNAF as being independently associated with ADRs. A putative toxicity relationship between CNAF and predicted probability of ADR was established.

Conclusions

Several patient variables were associated with impaired CLNAF, and elevated CNAF were associated with ADRs. Additional studies assessing the utility of nafcillin therapeutic drug monitoring to minimize toxicity are warranted.
Cyclophilin and enolase are the most prevalent conidial antigens of Lomentospora prolificans recognized by healthy human salivary IgA and cross‐react with Aspergillus fumigatus
Authors: Buldain Idoia , Ramirez‐Garcia Andoni , Pellon Aize , Antoran Aitziber , Sevilla Maria Jesus , Rementeria Aitor , Hernando Fernando L.
Published: August 2016

Purpose

The study of the immunocompetent airways immune response may provide important information to improve the therapeutic efficacy against Lomentospora (Scedosporium) prolificans. So, this study aimed to identify the most prevalent conidial antigens of this multiresistant fungus recognized by healthy human salivary immunoglobulin A, and to study their expression and cross‐reactivity with other fungal species.

Experimental design

Twenty saliva from immunocompetent donors were used to detect and identify the immunoreactive proteins by 2D immunoblotting and LC‐MS/MS. Moreover, anti‐Aspergillus antibodies were purified to study their cross‐reactivity.

Results

Ten proteins of L. prolificans conidia showed reactivity with more than 50% of the saliva samples. Among them, cyclophilin and enolase were the most prevalent antigens recognized by 85 and 80% of the samples, respectively. These enzymes were also identified on the cell wall surface of L. prolificans and on the immunomes of Scedosporium apiospermum and Scedosporium aurantiacum. Additionally, they showed cross‐reactivity with the most common pathogenic filamentous fungus Aspergillus fumigatus.

Conclusion and clinical relevance

These results show that the immunocompetent immune response might offer a pan‐fungal recognition of conserved antigens such as enolase and cyclophilins, making them potential candidates for study as therapeutic targets.
Higher groupoid bundles, higher spaces, and self‐dual tensor field equations
Authors: Jurčo Branislav , Sämann Christian , Wolf Martin
Published: August 2016

We develop a description of higher gauge theory with higher groupoids as gauge structure from first principles. This approach captures ordinary gauge theories and gauged sigma models as well as their categorifications on a very general class of (higher) spaces comprising presentable differentiable stacks, as e.g. orbifolds. We start off with a self‐contained review on simplicial sets as models of (∞, 1)‐categories. We then discuss principal bundles in terms of simplicial maps and their homotopies. We explain in detail a differentiation procedure, suggested by Ševera, that maps higher groupoids to ‐algebroids. Generalising this procedure, we define connections for higher groupoid bundles. As an application, we obtain six‐dimensional superconformal field theories via a Penrose–Ward transform of higher groupoid bundles over a twistor space. This construction reduces the search for non‐Abelian self‐dual tensor field equations in six dimensions to a search for the appropriate (higher) gauge structure. The treatment aims to be accessible to theoretical physicists.
The crystal structure of Clostridium perfringens SleM, a muramidase involved in cortical hydrolysis during spore germination
Authors: Al‐Riyami Bahja , Üstok Fatma Işık , Stott Katherine , Chirgadze Dimitri Y. , Christie Graham
Published: August 2016

Clostridium perfringens spores employ two peptidoglycan lysins to degrade the spore cortex during germination. SleC initiates cortex hydrolysis to generate cortical fragments that are degraded further by the muramidase SleM. Here, we present the crystal structure of the C. perfringens S40 SleM protein at 1.8 Å. SleM comprises an N‐terminal catalytic domain that adopts an irregular α/β‐barrel fold that is common to GH25 family lysozymes, plus a C‐terminal fibronectin type III domain. The latter is involved in forming the SleM dimer that is evident in both the crystal structure and in solution. A truncated form of SleM that lacks the FnIII domain shows reduced activity against spore sacculi indicating that this domain may have a role in facilitating the position of substrate with respect to the enzyme's active site. Proteins 2016; 84:1681–1689. © 2016 Wiley Periodicals, Inc.
Facile preparation of Au(111)/mica substrates for high‐quality graphene nanoribbon synthesis
Authors: Hell M. G. , Senkovskiy B. V. , Fedorov A. V. , Nefedov A. , Wöll C. , Grüneis A.
Published: August 2016

A setup for the preparation of oriented Au(111)/mica thin films of 100 nm thickness as an active substrate for graphene nanoribbon growth is shown. Low‐energy electron diffraction shows that the Au(111) thin films have a single crystallographic orientation over the whole surface area. Graphene nanoribbons are synthesized by the bottom‐up approach via surface polymerization of precursor molecules that are evaporated onto the catalytically active Au(111)/mica substrate. The graphene nanoribbons are investigated by a combination of resonance Raman, X‐ray photoemission spectroscopy, and near‐edge X‐ray absorption fine structure spectroscopy confirming a nanoribbon quality equal to nanoribbons grown on commercially available single‐crystal Au(111) substrates. The present work, therefore, establishes the preparation of Au(111)/mica as an inexpensive and simple method to prepare substrates of desired shape and thickness for surface polymerization reactions which are of interest to a growing community of researchers working on graphene nanoribbons.
Bayesian adaptive patient enrollment restriction to identify a sensitive subpopulation using a continuous biomarker in a randomized phase 2 trial
Authors: Ohwada Shoichi , Morita Satoshi
Published: August 2016

With the development of molecular targeted drugs, predictive biomarkers have played an increasingly important role in identifying patients who are likely to receive clinically meaningful benefits from experimental drugs (i.e., sensitive subpopulation) even in early clinical trials. For continuous biomarkers, such as mRNA levels, it is challenging to determine cutoff value for the sensitive subpopulation, and widely accepted study designs and statistical approaches are not currently available. In this paper, we propose the Bayesian adaptive patient enrollment restriction (BAPER) approach to identify the sensitive subpopulation while restricting enrollment of patients from the insensitive subpopulation based on the results of interim analyses, in a randomized phase 2 trial with time‐to‐endpoint outcome and a single biomarker. Applying a four‐parameter change‐point model to the relationship between the biomarker and hazard ratio, we calculate the posterior distribution of the cutoff value that exhibits the target hazard ratio and use it for the restriction of the enrollment and the identification of the sensitive subpopulation. We also consider interim monitoring rules for termination because of futility or efficacy. Extensive simulations demonstrated that our proposed approach reduced the number of enrolled patients from the insensitive subpopulation, relative to an approach with no enrollment restriction, without reducing the likelihood of a correct decision for next trial (no‐go, go with entire population, or go with sensitive subpopulation) or correct identification of the sensitive subpopulation. Additionally, the four‐parameter change‐point model had a better performance over a wide range of simulation scenarios than a commonly used dichotomization approach. Copyright © 2016 John Wiley & Sons, Ltd.
A generalized analytic solution to the win ratio to analyze a composite endpoint considering the clinical importance order among components
Authors: Dong Gaohong , Li Di , Ballerstedt Steffen , Vandemeulebroecke Marc
Published: August 2016

A composite endpoint consists of multiple endpoints combined in one outcome. It is frequently used as the primary endpoint in randomized clinical trials. There are two main disadvantages associated with the use of composite endpoints: a) in conventional analyses, all components are treated equally important; and b) in time‐to‐event analyses, the first event considered may not be the most important component. Recently Pocock et al. (2012) introduced the win ratio method to address these disadvantages. This method has two alternative approaches: the matched pair approach and the unmatched pair approach. In the unmatched pair approach, the confidence interval is constructed based on bootstrap resampling, and the hypothesis testing is based on the non‐parametric method by Finkelstein and Schoenfeld (1999). Luo et al. (2015) developed a close‐form variance estimator of the win ratio for the unmatched pair approach, based on a composite endpoint with two components and a specific algorithm determining winners, losers and ties. We extend the unmatched pair approach to provide a generalized analytical solution to both hypothesis testing and confidence interval construction for the win ratio, based on its logarithmic asymptotic distribution. This asymptotic distribution is derived via U‐statistics following Wei and Johnson (1985). We perform simulations assessing the confidence intervals constructed based on our approach versus those per the bootstrap resampling and per Luo et al. We have also applied our approach to a liver transplant Phase III study. This application and the simulation studies show that the win ratio can be a better statistical measure than the odds ratio when the importance order among components matters; and the method per our approach and that by Luo et al., although derived based on large sample theory, are not limited to a large sample, but are also good for relatively small sample sizes. Different from Pocock et al. and Luo et al., our approach is a generalized analytical method, which is valid for any algorithm determining winners, losers and ties. Copyright © 2016 John Wiley & Sons, Ltd.
In Vitro Assessment of Plants Growing in Cuba Belonging to Solanaceae Family Against Leishmania amazonensis
Authors: Monzote Lianet , Jiménez Jenny , Cuesta‐Rubio Osmany , Márquez Ingrid , Gutiérrez Yamile , da Rocha Cláudia Quintino , Marchi Mary , Setzer William N. , Vilegas Wagner
Published: August 2016

In this study, an in vitro antileishmanial assessment of plant extracts from 12 genera and 46 species growing in Cuba belonging to Solanaceae family was performed. A total of 226 extracts were screened against promastigotes of Leishmania amazonensis, and cytotoxicity of active extracts [median inhibitory concentration (IC50) promastigotes <100 µg/mL] was determined on peritoneal macrophage from BALB/c mice. Extracts that showed selective index >5 were then assayed against intracellular amastigote. Metabolomics analysis of promissory extracts was performed using chemical profile obtained by ultra performance liquid chromatography. Only 11 extracts (4.9%) from nine plants were selected as potentially actives: Brunfelsia cestroides A. Rich, Capsicum annuum L., Capsicum chinense Jacq., Cestrum nocturnum L., Nicotiana plumbaginifolia Viv., Solanum havanense Jacq., Solanum myriacanthum Dunal, Solanum nudum Dunal and Solanum seaforthianum And., with IC50 < 50 µg/mL and selectivity index >5. Metabolomics analysis demonstrated significant differences in the chemical profiles with an average of 42.8 (range 31–88) compounds from m/z 104 to 1477, which demonstrated the complex mixture of compounds. In addition, no common markers among active extracts were identified. The results demonstrate the importance of the Solanaceae family to search new antileishmanial agents, particularly in unexplored species of this family. Copyright © 2016 John Wiley & Sons, Ltd.
A composite likelihood approach in testing for Hardy Weinberg Equilibrium using family‐based genetic survey data
Authors: Wang Lingxiao , Graubard Barry I. , Li Yan
Published: August 2016

In population‐based household surveys, for example, the National Health and Nutrition Examination Survey, households are often sampled by stratified multistage cluster sampling, and multiple individuals related by blood are often sampled within households. Therefore, genetic data collected from these population‐based household surveys, called National Genetic Household Surveys, can be correlated because of two levels of correlation. One level of correlation is caused by the multistage geographical cluster sampling and the other is caused by biological inheritance among participants within the same sampled family. In this paper, we develop an efficient Hardy Weinberg Equilibrium (HWE) test utilizing pairwise composite likelihood methods that incorporate the sample weighting effect induced by the differential selection probabilities in complex sample designs, as well as the two‐level clustering (correlation) effects described above. Monte Carlo simulation studies show that the proposed HWE test maintains the nominal levels, and is more powerful than existing methods (Li et al. 2011) under various (non)informative sample designs that depend on genotypes (explicitly or implicitly), family relationships or both, especially when within‐household sampling depends on the genotypes. The developed tests are further evaluated using simulated genetic data based on the Hispanic Health and Nutrition Survey. Copyright © 2016 John Wiley & Sons, Ltd.
Multiple imputation of completely missing repeated measures data within person from a complex sample: application to accelerometer data in the National Health and Nutrition Examination Survey
Authors: Liu Benmei , Yu Mandi , Graubard Barry I. , Troiano Richard P. , Schenker Nathaniel
Published: August 2016

The Physical Activity Monitor component was introduced into the 2003–2004 National Health and Nutrition Examination Survey (NHANES) to collect objective information on physical activity including both movement intensity counts and ambulatory steps. Because of an error in the accelerometer device initialization process, the steps data were missing for all participants in several primary sampling units, typically a single county or group of contiguous counties, who had intensity count data from their accelerometers. To avoid potential bias and loss in efficiency in estimation and inference involving the steps data, we considered methods to accurately impute the missing values for steps collected in the 2003–2004 NHANES. The objective was to come up with an efficient imputation method that minimized model‐based assumptions. We adopted a multiple imputation approach based on additive regression, bootstrapping and predictive mean matching methods. This method fits alternative conditional expectation (ace) models, which use an automated procedure to estimate optimal transformations for both the predictor and response variables. This paper describes the approaches used in this imputation and evaluates the methods by comparing the distributions of the original and the imputed data. A simulation study using the observed data is also conducted as part of the model diagnostics. Finally, some real data analyses are performed to compare the before and after imputation results. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
High Volumetric Energy Density Asymmetric Supercapacitors Based on Well‐Balanced Graphene and Graphene‐MnO2 Electrodes with Densely Stacked Architectures
Authors: Sheng Lizhi , Jiang Lili , Wei Tong , Fan Zhuangjun
Published: August 2016

The well‐matched electrochemical parameters of positive and negative electrodes, such as specific capacitance, rate performance, and cycling stability, are important for obtaining high‐performance asymmetric supercapacitors. Herein, a facile and cost‐effective strategy is demonstrated for the fabrication of 3D densely stacked graphene (DSG) and graphene‐MnO2 (G‐MnO2) architectures as the electrode materials for asymmetric supercapacitors (ASCs) by using MnO2‐intercalated graphite oxide (GO‐MnO2) as the precursor. DSG has a stacked graphene structure with continuous ion transport network in‐between the sheets, resulting in a high volumetric capacitance of 366 F cm–3, almost 2.5 times than that of reduced graphene oxide, as well as long cycle life (93% capacitance retention after 10 000 cycles). More importantly, almost similar electrochemical properties, such as specific capacitance, rate performance, and cycling stability, are obtained for DSG as the negative electrode and G‐MnO2 as the positive electrode. As a result, the assembled ASC delivers both ultrahigh gravimetric and volumetric energy densities of 62.4 Wh kg–1 and 54.4 Wh L–1 (based on total volume of two electrodes) in 1 m Na2SO4 aqueous electrolyte, respectively, much higher than most of previously reported ASCs in aqueous electrolytes.
Exploring Structural Patterns Across Evolved and Designed Systems: A Network Perspective
Authors: Ellinas Christos , Allan Neil , Johansson Anders
Published: August 2016

Our desire to deliver increased functionality while setting tighter operational and regulative boundaries has fueled a recent influx of highly coupled systems. Nonetheless, our current capacity to successfully deliver them is still in its infancy. Understanding how such Designed systems are structured, along with how they compare to their naturally Evolved counterparts, can play an important role in bettering our capacity to do so. Based on this premise, the structural patterns underlying a wide range of seemingly unrelated systems are uncovered using tools from network science. By doing so, structural patterns emerge and are subsequently used to highlight both similarities and differences between the two classes of systems. With a focus on the Designed class, and assuming that increased structural variety fuels design uncertainty, it is shown that their adherence to statistical normality (i.e., expected vs. encountered patterns and statistical correlations between combinations of such patterns) is rather limited. Insight of this sort has both theoretical (context agnostic approaches are increasingly relevant within the domain of Systems Engineering, yet are rarely used) and practical (transferability of knowledge) implications.
Disentangling the Value Creation Mechanism in Cross‐Border Acquisitions: A Process‐Oriented Approach
Authors: Wang Daojuan , Sørensen Olav Jull , Moini Hamid
Published: August 2016

This study investigates the value creation mechanism in cross‐border acquisitions (CBAs) by employing a structural equation modeling technique and surveying 103CBAsperformed by Nordic firms. The results reveal that resource possession, resource picking, and resource utilization are three important strategic dimensions for realizing synergy and creating value inCBAs. Furthermore, mediation analysis shows that the two acquisition‐based dynamic capabilities—value identification and resource reconfiguration—act as important mediators in how the joining firms’ resource base impacts acquisition outcomes. The results shed light on the mechanisms through which the constructs influence value creation inCBAsand highlight the procedural and dynamic character of these determinants. The results also indicate that an integrative and process perspective, such as the “input‐process‐output” model proposed in this study, is an important step forward in merger and acquisition (M&A) research. Moreover, numerous research findings offer tactical implications for international acquirers. © 2016 Wiley Periodicals, Inc.
Subcarrier grouping with environmental sensing for MIMO‐OFDM systems over correlated double‐selective fading channels
Authors: Lu Jiaxun , Chen Zhengchuan , Fan Pingyi , Leatief Khaled B.
Published: August 2016

Multiple‐Input, Multiple‐Output (MIMO)‐orthogonal frequency division multiplexing (OFDM) is a promising technique in 5G wireless communications. In high‐mobility scenarios, the transmission environments are time‐varying and/or the relative moving velocity between the transmitter and receiver is also time‐varying. In the literature, most of previous works mainly focused on fixed subcarrier group size and precoded the MIMO signals with unitary channel state information. In this way, the subcarrier grouping may naturally lead to big loss of channel capacity in high‐mobility scenarios because of the channel state information difference on the subcarriers in each group. To employ the MIMO‐OFDM technique, adaptive subcarrier grouping scheme may be an efficient way. In this paper, we first consider MIMO‐OFDM systems over double‐selective i.i.d. Rayleigh channels and investigate the quantitative relation between subcarrier group size and capacity loss theoretically. With developed theoretical results, we also propose an adaptive subcarrier grouping scheme to satisfy the preset capacity loss threshold by adjusting grouping size with the sensed environmental information and mobile velocity. Theoretical analysis and simulation results show that to achieve a better system capacity, a sparse scattering, lower signal‐to‐noise ratio, and lower velocity as well as properly large antenna number are matched with larger subcarrier group size. One important observation is that if the antenna number is too large and higher than a threshold, which will not bring any additional gain to the subcarrier grouping. That is, the system capacity loss will converge to a lower bound expeditiously with respect to antenna number, which is given in theory also. Copyright © 2016 John Wiley & Sons, Ltd.
Diagnostic and prognostic value of in vivo proton MR spectroscopy for Zellweger syndrome spectrum patients
Authors: Rosewich H. , Dechent P. , Krause C. , Ohlenbusch A. , Brockmann K. , Gärtner J.
Published: August 2016

Defects in the biogenesis of peroxisomes cause a clinically and genetically heterogeneous group of neurometabolic disorders, the Zellweger syndrome spectrum (ZSS). Diagnosis predominantly is based on characteristic clinical symptoms, a typical biochemical profile, as well as on identification of the molecular defect in any of the 12 known human PEX genes. The diagnostic workup can be hindered if the typical clinical symptoms are missing and predicting the clinical course of a given patient is almost unfeasible. As a safe and noninvasive method to analyze specific chemical compounds in localized brain regions, in vivo proton magnetic resonance spectroscopy (MRS) can provide an indication in this diagnostic process and may help predict the clinical course. However, to date, there are very few reports on this topic. In this study, we performed localized in vivo proton MRS without confounding contributions from T1‐ and T2‐relaxation effects at 2 Tesla in a comparably large group of seven ZSS patients. Patients’ absolute metabolite concentrations in cortical gray matter, white matter, and basal ganglia were assessed and compared with age‐matched control values. Our results confirm and extend knowledge about in vivo MRS findings in ZSS patients. Besides affirmation of nonspecific reduction of N‐acetylaspartate + N‐acetylaspartylglutamate (tNAA) in combination with lipid accumulation as a diagnostic hint for this disease group, the amount of tNAA loss seems to reflect disease burden and may prove to be of prognostic value regarding the clinical course of an already diagnosed patient.