bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Meteorological Analogues for Reordering Postprocessed Precipitation Ensembles in Hydrological Forecasting
Authors: Bellier Joseph , Bontron Guillaume , Zin Isabella
Published: November 2017

Meteorological ensemble forecasts are nowadays widely used as input of hydrological models for probabilistic streamflow forecasting. These forcings are frequently biased and have to be statistically postprocessed, using most of the time univariate techniques that apply independently to individual locations, lead times and weather variables. Postprocessed ensemble forecasts therefore need to be reordered so as to reconstruct suitable multivariate dependence structures. The Schaake shuffle and ensemble copula coupling are the two most popular methods for this purpose. This paper proposes two adaptations of them that make use of meteorological analogues for reconstructing spatiotemporal dependence structures of precipitation forecasts. Performances of the original and adapted techniques are compared through a multistep verification experiment using real forecasts from the European Centre for Medium‐Range Weather Forecasts. This experiment evaluates not only multivariate precipitation forecasts but also the corresponding streamflow forecasts that derive from hydrological modeling. Results show that the relative performances of the different reordering methods vary depending on the verification step. In particular, the standard Schaake shuffle is found to perform poorly when evaluated on streamflow. This emphasizes the crucial role of the precipitation spatiotemporal dependence structure in hydrological ensemble forecasting.
Cancer Vaccines
Authors: Smith Peter L , Dalgleish Angus G
Published: November 2017

Cancer vaccines have been studied for approximately 40 years. During this time, a growing number of cancer antigen and vaccine platforms have been developed and a large number of clinical trials have been performed. These trials have regularly demonstrated an ability to activate antitumour immune responses and instances of clinical efficacy in responding patients. However, very few vaccines have achieved clinical end points in phase III trials and only one vaccine has been licenced by the FDA. With some notable exceptions, the disappointing performance of therapeutic cancer vaccines is due to a number of factors. However, recent developments in vaccination, combination immunotherapy and recent research detailing the immune suppression mediated by the tumour microenvironment offer new opportunities to realise the promise of therapeutic cancer vaccination.

Key Concepts

Cancer vaccines induce antitumour immune responses.

Cancer vaccines have yet to realise their potential in cancer immunotherapy.

The tumour microenvironment inhibits immune responses induced by cancer vaccines.

Combination therapy has the potential to improve the efficacy of cancer vaccination.

Cancer vaccines.
H
alopenitus
Authors: Ventosa Antonio , Amoozegar Mohammad A.
Published: November 2017

Ha.lo.pe'ni.tus. Gr. N.
hals, halos
salt; L. masc. adj.
penitus
inner, interior; N.L. masc. n.
Halopenitus
intended to mean an archaeon isolated from an inland salt lake.

Euryarchaeota / Halobacteria / Haloferacales / Halorubraceae / Halopenitus

The genus
Halopenitus
is classified within the family
Halorubraceae
, order
Haloferacales
, in the class
Halobacteria
. Phylogenetically is related to the genera
Halorubrum
,
Halohasta
, and
Halonotius
. The cells are pleomorphic, from rods to triangular or disk shaped, and stain Gram‐negative. Colonies are pale pink to red‐pigmented. They are extreme halophiles, growing in media containing 0.9–5.0 M NaCl. Polar lipids are phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, unidentified glycolipids, and minor phospholipids. They respiratory lipoquinone present is MK‐8(II‐H
2
). Currently, the genus includes three species:
Halopenitus persicus
(type species of the genus),
Halopenitus malekzadehii
, and
Halopenitus salinus
. The strains of these species were isolated from Aran‐Bidgol salt lake, Iran, and from commercial preparation of the salted brown alga
Laminaria
.

DNA G + C content (mol%)
: 63.8–66.0 (HPLC).

Type species
:
Halopenitus persicus
Amoozegar, Makhdoumi‐Kakhki, Shahzadeh Fazeli, Azarbaijani and Ventosa 2012, 1935
VP
.
Hippocampal sparing approach in fractionated stereotactic brain VMAT radio therapy: A retrospective feasibility analysis
Authors: Daniela Falco Maria , Giancaterino Stefano , D'Andrea Marco , Gimenez De Lorenzo Ramon , Trignani Marianna , Caravatta Luciana , Di Carlo Clelia , Di Biase Saide , Allajbej Albina , Genovesi Domenico
Published: November 2017

Volumetric Modulated Arc Therapy (VMAT) techniques for fractioned stereotactic brain radiotherapy (FSBRT) can achieve highly conformal dose distribution to intracranial lesions. However, they can potentially increase the dose to hippocampus (H) causing neurocognitive toxicity during the first four months after irradiation. The purpose of this study was to assess the feasibility of hippocampal‐sparing (HS) treatment plans in 22 patients with brain metastasis treated with VMAT technique. Firstly, we retrospectively analyzed hippocampal doses in all 22 VMAT original (not hippocampal‐sparing, NHS) plans. Plans with hippocampal dose exceeding constraints (9 out of 22) were re‐planned considering dose constraints on the hippocampus (H) and on hippocampal avoidance zone (HAZ) generated using 5 mm isotropic margin to the hippocampus. Conformity (CI) and homogeneity indexes (HI) on the target and MUs, were maintained as close as possible to the original plans. Mean CINHS and CIHS obtained were: 0.79 ± 0.11 and 0.81 ± 0.10, respectively (P = 0.75); mean HINHS and HIHS were 1.05 ± 0.02 and 1.04 ± 0.01 respectively (P = 0.72). In both sets of plans, the mean MU values were similar: 1033 ± 275 and 1022 ± 234 for NHS and HS respectively. In HS plans, the mean hippocampal dose was decreased by an average of 35%. After replanning, the Dmax (21.3 Gy) for HAZ and H was met by 45% (4/9) and 78% (7/9) of the NHS plans, respectively. The worst results were obtained for cases with target volumes extention closer than 12 mm to H, because of the difficulty to spare hippocampus without compromising target coverage. After replanning D40% constraint value (7.3 Gy) was met by all the 9 NHS plans. In conclusion, this study suggests that an hippocampal‐sparing approach to FSBRT is feasible resulting in a decrease in the dose to the hippocampus without any loss in conformity or increase in treatment time.
Normalize the response of EPID in pursuit of linear accelerator dosimetry standardization
Authors: Cai Bin , Goddu S. Murty , Yaddanapudi Sridhar , Caruthers Douglas , Wen Jie , Noel Camille , Mutic Sasa , Sun Baozhou
Published: November 2017

Normalize the response of electronic portal imaging device (EPID) is the first step toward an EPID‐based standardization of Linear Accelerator (linac) dosimetry quality assurance. In this study, we described an approach to generate two‐dimensional (2D) pixel sensitivity maps (PSM) for EPIDs response normalization utilizing an alternative beam and dark‐field (ABDF) image acquisition technique and large overlapping field irradiations. The automated image acquisition was performed by XML‐controlled machine operation and the PSM was generated based on a recursive calculation algorithm for Varian linacs equipped with aS1000 and aS1200 imager panels. Cross‐comparisons of normalized beam profiles and 1.5%/1.5 mm 1D Gamma analysis was adopted to quantify the improvement of beam profile matching before and after PSM corrections. PSMs were derived for both photon (6, 10, 15 MV) and electron (6, 20 MeV) beams via proposed method. The PSM‐corrected images reproduced a horn‐shaped profile for photon beams and a relative uniform profiles for electrons. For dosimetrically matched linacs equipped with aS1000 panels, PSM‐corrected images showed increased 1D‐Gamma passing rates for all energies, with an average 10.5% improvement for crossline and 37% for inline beam profiles. Similar improvements in the phantom study were observed with a maximum improvement of 32% for 15 MV and 22% for 20 MeV. The PSM value showed no significant change for all energies over a 3‐month period. In conclusion, the proposed approach correct EPID response for both aS1000 and aS1200 panels. This strategy enables the possibility to standardize linac dosimetry QA and to benchmark linac performance utilizing EPID as the common detector.
Early Rheumatoid Arthritis Presentation, Treatment, and Outcomes in Aboriginal Patients in Canada: A Canadian Early Arthritis Cohort Study Analysis
Authors: Nagaraj Sujay , Barnabe Cheryl , Schieir Orit , Pope Janet , Bartlett Susan J. , Boire Gilles , Keystone Edward , Tin Diane , Haraoui Boulos , Thorne J. Carter , Bykerk Vivian P. , Hitchon Carol ,   the Canadian Early Arthritis Cohort Study Investigators
Published: November 2017

Objective

Health inequities exist in chronic diseases for Aboriginal people. This study compared early rheumatoid arthritis (RA) presentation, treatment, and outcomes between Aboriginal and white patients in a large Canadian cohort study.

Methods

Longitudinal data from the Canadian Early Arthritis Cohort, a prospective multicenter early RA study, were analyzed for participants who self‐identified as Aboriginal or white ethnicity. Disease characteristics at presentation, prognostic factors, frequency of remission, and disease‐modifying therapy strategies were contrasted between population groups. Linear mixed models were used to estimate rates of change for disease activity measures over a 5‐year period.

Results

At baseline, 2,173 participants (100 Aboriginal and 2,073 white) had similar mean ± SD symptom duration (179 ± 91 days), 28‐joint Disease Activity Scores (DAS28; 4.87 ± 1.48), and Health Assessment Questionnaire (0.88 ± 0.68) scores. Factors associated with poor prognosis were more frequently present in Aboriginal participants, but disease‐modifying therapy selection and frequency of therapy escalation was similar between the 2 groups. DAS28 remission was achieved less frequently in Aboriginal than in white participants (adjusted odds ratio 0.39 [95% confidence interval 0.25–0.62]). Results were primarily driven by slower improvement in swollen joint counts and nonsignificant improvement in patient global scores in Aboriginal participants. Pain levels remained higher in Aboriginal patients.

Conclusion

Aboriginal early RA patients experienced worse disease outcomes than their white counterparts. This may reflect unmeasured biologic differences and/or disparities in prognostic factors informed by inequities in determinants of health. The appropriateness of current treatment strategies applied in different contexts should be considered.
A Multifunctional Polymeric Periodontal Membrane with Osteogenic and Antibacterial Characteristics
Authors: Nasajpour Amir , Ansari Sahar , Rinoldi Chiara , Rad Afsaneh Shahrokhi , Aghaloo Tara , Shin Su Ryon , Mishra Yogendra Kumar , Adelung Rainer , Swieszkowski Wojciech , Annabi Nasim , Khademhosseini Ali , Moshaverinia Alireza , Tamayol Ali
Published: November 2017

Periodontitis is a prevalent chronic, destructive inflammatory disease affecting tooth‐supporting tissues in humans. Guided tissue regeneration strategies are widely utilized for periodontal tissue regeneration generally by using a periodontal membrane. The main role of these membranes is to establish a mechanical barrier that prevents the apical migration of the gingival epithelium and hence allowing the growth of periodontal ligament and bone tissue to selectively repopulate the root surface. Currently available membranes have limited bioactivity and regeneration potential. To address such challenges, an osteoconductive, antibacterial, and flexible poly(caprolactone) (PCL) composite membrane containing zinc oxide (ZnO) nanoparticles is developed. The membranes are fabricated through electrospinning of PCL and ZnO particles. The physical properties, mechanical characteristics, and in vitro degradation of the engineered membrane are studied in detail. Also, the osteoconductivity and antibacterial properties of the developed membrane are analyzed in vitro. Moreover, the functionality of the membrane is evaluated with a rat periodontal defect model. The results confirmed that the engineered membrane exerts both osteoconductive and antibacterial properties, demonstrating its great potential for periodontal tissue engineering.
Bending‐Tolerant Anodes for Lithium‐Metal Batteries
Authors: Wang Aoxuan , Tang Shan , Kong Debin , Liu Shan , Chiou Kevin , Zhi Linjie , Huang Jiaxing , Xia Yong‐Yao , Luo Jiayan
Published: November 2017

Bendable energy‐storage systems with high energy density are demanded for conformal electronics. Lithium‐metal batteries including lithium–sulfur and lithium–oxygen cells have much higher theoretical energy density than lithium‐ion batteries. Reckoned as the ideal anode, however, Li has many challenges when directly used, especially its tendency to form dendrite. Under bending conditions, the Li‐dendrite growth can be further aggravated due to bending‐induced local plastic deformation and Li‐filaments pulverization. Here, the Li‐metal anodes are made bending tolerant by integrating Li into bendable scaffolds such as reduced graphene oxide (r‐GO) films. In the composites, the bending stress is largely dissipated by the scaffolds. The scaffolds have increased available surface for homogeneous Li plating and minimize volume fluctuation of Li electrodes during cycling. Significantly improved cycling performance under bending conditions is achieved. With the bending‐tolerant r‐GO/Li‐metal anode, bendable lithium–sulfur and lithium–oxygen batteries with long cycling stability are realized. A bendable integrated solar cell–battery system charged by light with stable output and a series connected bendable battery pack with higher voltage is also demonstrated. It is anticipated that this bending‐tolerant anode can be combined with further electrolytes and cathodes to develop new bendable energy systems.
Nanomicelle‐Assisted Targeted Ocular Delivery with Enhanced Antiinflammatory Efficacy In Vivo
Authors: Weng Yu‐Hua , Ma Xiao‐Wei , Che Jing , Li Chan , Liu Juan , Chen Shi‐Zhu , Wang Yu‐Qin , Gan Ya‐Ling , Chen Hao , Hu Zhong‐Bo , Nan Kai‐Hui , Liang Xing‐Jie
Published: November 2017

Ocular inflammations are common diseases that may lead to serious vision‐threatening obstacles. Eye drops for antiinflammation therapy need to be administered multiple times daily at a high dosage due to the rapid precorneal removal and low bioavailability of drugs. To overcome these problems, a cRGD‐functionalized DSPE‐PEG2000 nanomicelle (DSPE‐PEG2000‐cRGD) encapsulated with flurbiprofen is proposed. The tailored nanomicelles trigger specific binding to integrin receptors on the ocular surface, which leads to rapid and robust mucoadhesion, superior ocular surface retention, and transcorneal penetration behaviors of nanomicelles. Due to the enhanced drug delivery on ocular surface and in aqueous humor, the functionalized nanoformulation significantly improves ocular antiinflammation efficacy at a low dosage by blocking the synthesis of inflammatory mediators and cytokines. The present study demonstrates a promising strategy that uses a functional peptide combined with nanomicelles for targeted delivery to the eye in ophthalmologic applications.
Verifying the Rechargeability of Li‐CO2 Batteries on Working Cathodes of Ni Nanoparticles Highly Dispersed on N‐Doped Graphene
Authors: Zhang Zhang , Wang Xin‐Gai , Zhang Xu , Xie Zhaojun , Chen Ya‐Nan , Ma Lipo , Peng Zhangquan , Zhou Zhen
Published: November 2017

Li‐CO2 batteries could skillfully combine the reduction of “greenhouse effect” with energy storage systems. However, Li‐CO2 batteries still suffer from unsatisfactory electrochemical performances and their rechargeability is challenged. Here, it is reported that a composite of Ni nanoparticles highly dispersed on N‐doped graphene (Ni‐NG) with 3D porous structure, exhibits a superior discharge capacity of 17 625 mA h g−1, as the air cathode for Li‐CO2 batteries. The batteries with these highly efficient cathodes could sustain 100 cycles at a cutoff capacity of 1000 mA h g−1 with low overpotentials at the current density of 100 mA g−1. Particularly, the Ni‐NG cathodes allow to observe the appearance/disappearance of agglomerated Li2CO3 particles and carbon thin films directly upon discharge/charge processes. In addition, the recycle of CO2 is detected through in situ differential electrochemical mass spectrometry. This is a critical step to verify the electrochemical rechargeability of Li‐CO2 batteries. Also, first‐principles computations further prove that Ni nanoparticles are active sites for the reaction of Li and CO2, which could guide to design more advantageous catalysts for rechargeable Li‐CO2 batteries.
Hybrid van der Waals SnO/MoS2 Heterojunctions for Thermal and Optical Sensing Applications
Authors: Wang Zhenwei , He Xin , Zhang Xi‐Xiang , Alshareef Husam N.
Published: November 2017

Emerging van der Waals heterojunctions (vdWH) containing 2D materials have shown exciting functionalities that surpass those of traditional devices based on bulk materials. In this Communication, a report on the properties of a 2D sulfide/oxide hybrid vdWH based on n‐type molybdenum disulfide (MoS2) and p‐type tin monoxide (SnO) is presented, with promising rectification, thermal‐sensing, and photosensing performance. Specifically, the hybrid SnO/MoS2 vdWH shows static rectification ratio of 2 × 102 with ideality factor of 2.3, and can operate at 100 Hz with good stability. The vdWH shows good temperature stability with reversible and reproducible current levels up to 110 °C, indicating its potential for thermal sensing applications. The sensitivity of current variation is calculated to be 0.0144 dec °C−1. Finally, maximum responsivity of 8.17 mA W−1 and external quantum efficiency of 2.14% have been achieved in photovoltaic measurements. The results suggest that MoS2–SnO hybrid vdWH are promising for various sensing applications.
More comprehensive 3D modeling of clay‐like material drying
Authors: Heydari M. , Khalili K. , Ahmadi‐Brooghani S. Y.
Published: November 2017

Drying process plays an important role in the manufacturing of many products such as ceramic, kitchenware and building materials, some of which have complex three‐dimensional (3D) geometry. To deal with many restrictions found in literatures, a 3D numerical approach was used to describe the drying process of a porous Clay‐like material. The problem investigated involves highly coupled equations considering heat, mass, and mechanical aspects. The model is validated through the comparison of experimental measurements with simulation result. Simulation results show that increasing the initial moisture content and reducing the initial temperature have the same privilege and without significant increase in drying time, it reduces slightly the amount of maximum stress but delays the occurrence time of maximum stress. The nonuniform heat expansion induced stresses are very small in comparison to nonuniform moisture shrinkage induced stresses and can be neglected in drying simulation. © 2017 American Institute of Chemical Engineers AIChE J, 64: 1469–1478, 2018
Amyotrophic lateral sclerosis—A case report and mechanistic review of the association with toluene and other volatile organic compounds
Authors: Ratner Marcia H. , Jabre Joe F. , Ewing William M. , Abou‐Donia Mohamed , Oliver L. Christine
Published: November 2017

Unmasking of latent neurodegenerative disease has been reported following exposure to chemicals that share one or more mechanisms of action in common with those implicated in the specific disease. For example, unmasking of latent Parkinson's disease (PD) has been associated with exposure to anti‐dopaminergic agents, while the progression of pre‐existing mild cognitive impairment and unmasking of latent Alzheimer's disease has been associated with exposure to general anesthetic agents which promote Aβ protein aggregation. This literature review and clinical case report about a 45‐year‐old man with no family history of motor neuron disease who developed overt symptoms of a neuromuscular disorder in close temporal association with his unwitting occupational exposure to volatile organic compounds (VOCs) puts forth the hypothesis that exposure to VOCs such as toluene, which disrupt motor function and increase oxidative stress, can unmask latent ALS type neuromuscular disorder in susceptible individuals.
Simultaneous Application of Photothermal Therapy and an Anti‐inflammatory Prodrug using Pyrene–Aspirin‐Loaded Gold Nanorod Graphitic Nanocapsules
Authors: Dong Qian , Wang Xuewei , Hu Xiaoxiao , Xiao Langqiu , Zhang Liang , Song Lijuan , Xu Minglu , Zou Yuxiu , Chen Long , Chen Zhuo , Tan Weihong
Published: November 2017

Photothermal therapy (PTT) has been extensively developed as an effective approach against cancer. However, PTT can trigger inflammatory responses, in turn simulating tumor regeneration and hindering subsequent therapy. A therapeutic strategy was developed to deliver enhanced PTT and simultaneously inhibit PTT‐induced inflammatory response. 1‐Pyrene methanol was utilize to synthesize the anti‐inflammatory prodrug pyrene–aspirin (P‐aspirin) with a cleavable ester bond and also facilitate loading the prodrug on gold nanorod (AuNR)‐encapsulated graphitic nanocapsule (AuNR@G), a photothermal agent, through π–π interactions. Such AuNR@G‐P‐aspirin complexes were used for near‐infrared laser‐triggered photothermal ablation of solid tumor and simultaneous inhibition of PTT‐induced inflammation through the release of aspirin in tumor milieu. This strategy showed excellent effects in vitro and in vivo.
Eine biokatalytische oxidative Kaskade für die Umsetzung von Fettsäuren zu α‐Ketosäuren mit interner H2O2‐Regeneration
Authors: Gandomkar Somayyeh , Dennig Alexander , Dordic Andela , Hammerer Lucas , Pickl Mathias , Haas Thomas , Hall Mélanie , Faber Kurt
Published: November 2017

Eine Wertschöpfung aus natürlichen Kohlenstoffquellen erfordert die Funktionalisierung von biobasierten Chemikalien. Eine atomeffiziente biokatalytische oxidative Kaskade wurde entwickelt, um aus gesättigten Fettsäuren α‐Ketosäuren herzustellen. Dafür wurde ein Cytochrom P450 im Peroxygenase‐Modus für die regioselektive α‐Hydroxylierung der Fettsäuren gemeinsam mit α‐Hydroxysäure‐Oxidase(n) für die nachfolgende enantioselektive Oxidation eingesetzt, was zu einer internen Regeneration des Oxidationsmittels H2O2 führte. Dadurch konnte die Zersetzung der Ketosäure unterdrückt werden, und die Lebensdauer des Biokatalysators wurde wenig beeinflusst. Die O2‐abhängige Kaskade beruht auf katalytischen Mengen an H2O2 und bildet Wasser als einziges Nebenprodukt. Aus Octansäure konnte unter milden Bedingungen 2‐Oxooctansäure in einer simultanen zweistufigen Eintopf‐Kaskade in wässrigem Puffer mit bis zu >99 % Umsatz ohne Anreicherung der Hydroxysäure hergestellt werden. Das Produkt wurde in präparativem Maßstab mit 91 % Ausbeute isoliert, und die Kaskade wurde für Fettsäuren mit verschiedenen Kettenlängen angewendet (C6:0 bis C10:0).
Serum sodium and chloride are inversely associated with dyskinesia in Parkinson's disease patients
Authors: Mao Cheng‐jie , Zhong Chong‐ke , Yang Yong , Yang Ya‐ping , Wang Fen , Chen Jing , Zhang Jin‐ru , Zhang Hui‐jun , Jin Hong , Xu Ling‐li , Huang Juan‐ying , Liu Chun‐Feng
Published: November 2017

Objective

We aim to report and evaluate the associations between serum sodium and chloride and dyskinesia in patients with Parkinson's disease. One hundred and two patients with Parkinson's disease were enrolled in this study.

Methods

Patients’ serum electrolytes including sodium, calcium, potassium, magnesium, and chloride were measured. Other demographic information was collected, and Unified Parkinson's disease rating scale and Hoehn and Yahr stage scale were also performed.

Results

Patients with dyskinesia tended to have longer duration of disease, higher daily levodopa‐equivalent dose, and Hoehn–Yahr stage, with lower serum sodium than those without dyskinesia. Spearman correlation analyses showed that serum sodium inversely correlated with duration of disease (r = −.218, p = .028), and positively correlated with serum chloride levels (r = .565, p < .001). Univariate logistic regression analysis found that duration of disease, daily levodopa‐equivalent dose, serum sodium, and serum chloride were associated with dyskinesia in Parkinson's disease patients (p < .05 for all). After adjusting for age, sex, age at onset of Parkinson's disease, medical history, and other covariates, serum sodium and chloride were still associated with dyskinesia, with corresponding Odd ratios 0.783 (95% confidence intervals, 0.642–0.955) and 0.796 (95% confidence intervals, 0.652–0.972), respectively.

Conclusion

Our findings indicated that serum sodium and chloride levels were inversely associated with dyskinesia in patients with Parkinson's disease. Further studies with large samples and range of serum sodium and chloride are needed.
Stakeholder Engagement in Sustainable Enterprise: Evolving a Conceptual Framework, and a Case Study of ITC
Authors: Anbarasan Periyasami , Sushil  
Published: November 2017

An intensive debate has been occurring among academics, consultants and corporate executives, resulting in many definitions of a more humane, more ethical and more transparent manner of conducting business. They have created, supported or criticized related concepts such as sustainable development, corporate citizenship, sustainable entrepreneurship, the triple bottom line, business ethics and corporate social responsibility (Van Marrewijk, ). In the midst of LPG (liberalization, privatization and globalization), with market expansion occurring and the customer base needing to be widened for long‐term profitability, can enterprise opt for sustainability through the stakeholder approach? Interestingly, the ITC (Imperial Tobacco Company) is a firm committed to the core values of sustainable development in agrobusiness and in other activities, which has made the corporation well known for its stand on sustainability. Hence, this study begins with a brief literature review on sustainable enterprise and an introduction to familiarize the reader with the case organization, to examine what has made the ITC remain a stalwart in sustainable development and to identify the factors that drive the ITC's vision of sustainability. Based on the identified factors, total interpretive structural modeling (TISM) has been used to evolve a framework of sustainable enterprises on the star model (Sushil, ), which explains the customer and the government as driving factors for sustainability along with the triple bottom line. To validate our study, data on surrogate measures of some of the variables have been taken from the annual reports of the ITC and the validation is performed using linear regression analysis. Finally, the future research scope and limitations of the study are discussed. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Costus spiralis (Jacq.) Roscoe: A Novel Source of Flavones with α‐Glycosidase Inhibitory Activity
Authors: de Oliveira Ana P. , Coppede Juliana S. , Bertoni Bianca W. , Crotti Antônio E. M. , França Suzelei C. , Pereira Ana Maria S. , Taleb‐Contini Silvia H.
Published: November 2017

Costus spiralis, a plant used in traditional Brazilian medicine for the treatment of complications in diabetes, was investigated. Assay of hexane, ethyl acetate, methanol, and aqueous fractions obtained by partition of a crude methanol extract of dried leaves of C. spiralis revealed that AGI activity was confined to the ethyl acetate fraction. Purification of this fraction yielded schaftoside and isoschaftoside. The AGI activities of the two flavones were lower than, but comparable with, that of the anti‐diabetic drug acarbose. In contrast, the IC50 value of the ethyl acetate fraction was 1.95‐, 2.34‐, and 2.22‐fold higher than those of acarbose, schaftoside, and isoschaftoside, respectively. The results demonstrate for the first time that schaftoside and isoschaftoside are responsible, in part, for the AGI activity of C. spiralis. Our study suggests that further investigations into C. spiralis may lead to the discovery of additional compounds with antihyperglycemic activity.
Photochemical Oxidative Coupling of 2‐Naphthols using a Hybrid Reduced Graphene Oxide/Manganese Dioxide Nanocomposite under Visible‐Light Irradiation
Authors: Kumar Anurag , Aathira M. S. , Pal Ujjwal , Jain Suman L.
Published: November 2017

We describe a simple, cost‐effective, efficient, and high‐yielding photocatalytic approach for the oxidative self‐dimerization of 2‐naphthols using a semiconductor–metal hybrid that consists of intercalated manganese dioxide nanoparticles in reduced graphene oxide (rGO/MnO2) under visible‐light irradiation. The desired photocatalyst was synthesized in a single step by mixing MnO2 nanoparticles with rGO ultrasonically. The hybrid photocatalyst exhibited a significantly higher activity than neat MnO2 nanoparticles and rGO, which is believed to be because of the synergistic effect of its components. To our knowledge, this hybrid rGO/MnO2 nanocomposite is the first heterogeneous, green photocatalyst for the oxidative coupling of 2‐naphthols under mild conditions.
Exploiting Synergies in Catalysis and Gas Sensing using Noble Metal‐Loaded Oxide Composites
Authors: Müller Sabrina A. , Degler David , Feldmann Claus , Türk Michael , Moos Ralf , Fink Karin , Studt Felix , Gerthsen Dagmar , Bârsan Nicolae , Grunwaldt Jan‐Dierk
Published: November 2017

Noble metal/metal oxide nanocomposites are very important in various fields of catalysis and play an evenly important role in gas sensing. Although there are many similarities regarding the choice of materials, the synthesis and the fundamental mechanisms, both research fields have been mostly treated independently up to now. In both fields, open questions regarding the elementary steps in the interaction of the gases with the active species and the role of the noble metal, the semiconducting metal oxide support and the interface remain. In this concept article, we first outline the importance of such composites in catalysis and gas sensing focussing on Pt/Pd, as well as CeO2 and SnO2 as transition metal oxides. Next, the state of art of both fundamental and relevant surface reactions and electronic mechanisms are described. Finally, we highlight the synergy of jointly exploring catalysis and gas sensing of noble metal/metal oxide nanocomposite materials and the benefit for both research fields if they are dealt with simultaneously using advanced characterization and operando methods, sophisticated preparation techniques, testing of the performance, and predictive theoretical modelling.
Constructing h‐BN/Bi2WO6 Quantum Dot Hybrid with Fast Charge Separation and Enhanced Photoelectrochemical Performance by using h‐BN for Hole Transfer
Authors: Li Junqi , Lei Nan , Guo Liu , Song Qianqian , Liang Zheng
Published: November 2017

Bi2WO6 quantum dot (QD)‐decorated hexagonal boron nitride (h‐BN) nanosheets were prepared by using a one‐step hydrothermal synthesis method. The Bi2WO6 QDs with a size of 4–8 nm are anchored uniformly on the h‐BN nanosheets with boron vacancies to form a h‐BN/Bi2WO6 QD hybrid. The h‐BN nanosheets not only function as a good support for Bi2WO6 QDs to block agglomeration, but also serve as a promoter for h+ transfer to improve the charge separation in the hybrid material. The photoelectrochemical (PEC) performance of the photoanodes was evaluated by using linear sweep voltammetry, electrochemical impedance spectroscopy, Bode plots, and Mott‐Schottky analyses. The results indicate that h‐BN/Bi2WO6 QD hybrids show enhanced PEC performance, which is mainly embodied in a higher photocurrent density, better electron transport properties, longer electrons lifetime, and increased carrier density. Finally, a possible mechanism for the enhanced PEC performance is proposed and discussed.
Application of image moments in MIA‐QSAR
Authors: Xu Min Li , Wang Xue , Li Bao Qiong , Zhai Hong Lin , Lu Shao Hua
Published: November 2017

Owing to the presence of some significant chemical information, the conventional images of molecular structures have been used in the studies of quantitative structure‐activity relationship by multivariate image analysis (MIA‐QSAR). In this contribution, we suggest that the Tchebichef moments (TMs) calculated directly from the grayscale images of molecular structures are used as molecular descriptors to build linear QSAR models by stepwise regression. The proposed approach was applied to QSAR research on a series of HIV‐1 non‐nucleoside reverse transcriptase inhibitors, and satisfactory results were obtained. Compared with several published methods, the results indicate that the TM method possesses higher accuracy and reliability. The TMs effectively decompose the image information of molecular structures at different levels without any pretreatment owing its very favorable multiresolution, holographic, and inherent invariance properties. Our study successfully extends the application of image moments to MIA‐QSAR research.
Redox‐Active Ligand‐Assisted Two‐Electron Oxidative Addition to Gallium(II)
Authors: Fedushkin Igor L. , Dodonov Vladimir A. , Skatova Alexandra A. , Sokolov Vladimir G. , Piskunov Alexander V. , Fukin Georgii K.
Published: November 2017

The reaction of digallane (dpp‐bian)Ga−Ga(dpp‐bian) (2) (dpp‐bian=1,2‐bis[(2,6‐diisopropylphenyl)imino]acenaphthene) with allyl chloride (AllCl) proceeded by a two‐electron oxidative addition to afford paramagnetic complexes (dpp‐bian)Ga(η1‐All)Cl (3) and (dpp‐bian)(Cl)Ga−Ga(Cl)(dpp‐bian) (4). Treatment of complex 4 with pyridine induced an intramolecular redox process, which resulted in the diamagnetic complex (dpp‐bian)Ga(Py)Cl (5). In reaction with allyl bromide, complex 2 gave metal‐ and ligand‐centered addition products (dpp‐bian)Ga(η1‐All)Br (6) and (dpp‐bian‐All)(Br)Ga−Ga(Br)(dpp‐bian‐All) (7). The reaction of digallane 2 with Ph3SnNCO afforded (dpp‐bian)Ga(SnPh3)2 (8) and (dpp‐bian)(NCO)Ga−Ga(NCO)(dpp‐bian) (9). Treatment of GaCl3 with (dpp‐bian)Na in diethyl ether resulted in the formation of (dpp‐bian)GaCl2 (10). Diorganylgallium derivatives (dpp‐bian)GaR2 (R=Ph, 11; tBu, 14; Me, 15; Bn, 16) and (dpp‐bian)Ga(η1‐All)R (R=nBu, 12; Cp, 13) were synthesized from complexes 3, 10, Bn2GaCl, or tBu2GaCl by salt metathesis. The salt elimination reaction between (dpp‐bian)GaI2 (17) and tBuLi was accompanied by reduction of both the metal and the dpp‐bian ligand, which resulted in digallane 2 as the final product. Similarly, the reaction of complex 10 with MentMgCl (Ment=menthyl) proceeded with reduction of the dpp‐bian ligand to give the diamagnetic complex [(dpp‐bian)GaCl2][Mg2Cl3(THF)6] (18). Compounds 11, 12, 13, 15, and 16 were thermally robust, whereas compound 14 decomposed when heated at reflux in toluene to give complex (dpp‐bian‐tBu)GatBu2 (19). Both complexes 7 and 19 contain R‐substituted dpp‐bian ligand: in the former compound the allyl group was attached to the imino‐carbon atom, whereas in complex 19, the tBu group was situated on the naphthalene ring. Crystal structures of complexes 3, 8, 9, 10, 13, 14, 18, and 19 were determined by single‐crystal X‐ray analysis. The presence of dpp‐bian radical anions in 3, 6, 8, and 10–16 was determined by ESR spectroscopy.
Regio‐ and Enantioselective Allylic Amination of Aliphatic MBH Adducts with N‐Heteroaromatics
Authors: Wang Haixia , Yu Lulu , Xie Mingsheng , Wu Jiang , Qu Guirong , Ding Kuiling , Guo Haiming
Published: November 2017

Palladium‐catalyzed regio‐ and enantioselective allylic amination of aliphatic Morita‐Baylis–Hillman (MBH) adducts with N‐heteroaromatic nucleophiles (e.g., benzimidazole, 4,5‐diphenylimidazole, benzotriazole, and purines) was achieved by using a spiroketal‐based diphosphine (SKP) ligand, and afforded a range of chiral, branched N‐allyl products with high selectivity.
Protein Recognition by Functionalized Sulfonatocalix[4]arenes
Authors: Doolan Aishling M. , Rennie Martin L. , Crowley Peter B.
Published: November 2017

The interactions of two mono‐functionalized sulfonatocalix[4]arenes with cytochrome c were investigated by structural and thermodynamic methods. The replacement of a single sulfonate with either a bromo or a phenyl substituent resulted in altered recognition of cytochrome c as evidenced by X‐ray crystallography. The bromo‐substituted ligand yielded a new binding mode in which a self‐encapsulated calixarene dimer contributed to crystal packing. This ligand also formed a weak halogen bond with the protein. The phenyl‐substituted ligand was bound to Lys4 of cytochrome c, in a 1.7 Å resolution crystal structure. A dimeric packing arrangement mediated by ligand–ligand contacts in the crystal suggested a possible assembly mechanism. The different protein recognition properties of these calixarenes are discussed.
Implementation of precision medicine in clinical trials in thoracic oncology: Which are the hurdles?
Authors: Scagliotti Giorgio V.
Published: November 2017

Precision medicine quite likely will be implemented at a different pace than originally hypothesized, but it is definitely the way to move forward. Even from a medical oncology perspective, a clear understanding of the changes in a molecular pathway and the timely application of a diagnostic assay are critical steps to ultimately deliver a better treatment choice to each individual patient with non–small cell lung cancer.

See also pages 4800‐7.
Non–small cell lung cancer clinical trials requiring biopsies with biomarker‐specific results for enrollment provide unique challenges
Authors: Spiegel Marshall L. , Goldman Jonathan W. , Wolf Brian R. , Nameth Danielle J. , Grogan Tristan R. , Lisberg Aaron E. , Wong Deborah J. L. , Ledezma Blanca A. , Mendenhall Melody A. , Genshaft Scott J. , Gutierrez Antonio J. , Abtin Fereidoun , Wallace W. Dean , Adame Carlos R. , McKenzie Jordan R. , Abarca Phillip A. , Li Alice J. , Strunck Jennifer L. , Famenini Sina , Carroll James M. , Tucker D. Andrew , Sauer Lauren M. , Moghadam Nima M. , Elashoff David A. , Abaya Christina D. , Brennan Meghan B. , Garon Edward B.
Published: November 2017

BACKGROUND

Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated.

METHODS

The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California‐Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment.

RESULTS

In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker‐eligible patients.

CONCLUSIONS

Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800‐7. © 2017 American Cancer Society.
Relationship between the left ventricular size and the amount of trabeculations
Authors: Paun Bruno , Bijnens Bart , Butakoff Constantine
Published: November 2017

Contemporary imaging modalities offer noninvasive quantification of myocardial deformation; however, they make gross assumptions about internal structure of the cardiac walls. Our aim is to study the possible impact of the trabeculations on the stroke volume, strain, and capacity of differently sized ventricles. The cardiac left ventricle is represented by an ellipsoid and the trabeculations by a tissue occupying a fixed volume. The ventricular contraction is modeled by scaling the ellipsoid whereupon the measurements of longitudinal strain, end‐diastolic, end‐systolic, and stroke volumes are derived and compared. When the trabeculated and nontrabeculated ventricles, having the same geometry and deformation pattern, contain the same amount of blood and contract with the same strain, we observed an increased stroke volume in our model of the trabeculated ventricle. When these ventricles contain and eject the same amount of blood, we observed a reduced strain in the trabeculated case. We identified that a trade‐off between the strain and the amount of trabeculations could be reached with a 0.35‐ to 0.41‐cm dense trabeculated layer, without blood filled recesses (for a ventricle with end‐diastolic volume of about 150 mL). A trabeculated ventricle can work at lower strains compared to a nontrabeculated ventricle to produce the same stroke volume, which could be a possible explanation why athletes and pregnant women develop reversible signs of left ventricular noncompaction, since the trabeculations could help generating extra cardiac output. This knowledge might help to assess heart failure patients with dilated cardiomyopathies who often show signs of noncompaction.
Two Phase 1, Open‐Label, Single‐Dose, Randomized, Crossover Studies to Assess the Pharmacokinetics, Safety, and Tolerability of Orally Administered Granules of Secnidazole (2 g) in Healthy Female Volunteers Under Different Administration Conditions
Authors: Pentikis Helen S. , Adetoro Nikki
Published: November 2017

Bacterial vaginosis (BV) is the most common vaginal infection in reproductive‐age women and a significant risk factor for sexually transmitted diseases and pregnancy complications. Standard 5‐ to 7‐day antimicrobial treatments for BV are associated with high rates of recurrence and adverse events. SYM‐1219 is a novel granule formulation containing 2 g of secnidazole, developed as an oral, single‐dose BV treatment. Two phase 1, open‐label, single‐center, randomized, crossover trials (studies 102 and 103) assessed the pharmacokinetics and safety of SYM‐1219 single doses (≥7‐day washout between doses) in healthy, nonpregnant women aged 18 to 65 years inclusive. Study 102 compared SYM‐1219 in applesauce in fasted vs fed states. Study 103 compared SYM‐1219 (fasted) in pudding and yogurt vs applesauce. Studies 102 and 103 each dosed 24 subjects (mean [standard deviation] ages, 36 [1.8] and 40 [11.6] years, respectively). In both studies the 90% confidence intervals for all treatment comparisons of maximum plasma concentration, area under the concentration‐time curve from 0 to last measurable concentration and to infinity, geometric mean ratios were within 80% to 125%, demonstrating bioequivalence. In both studies median fasted time to maximum plasma concentration was 4 hours (6 hours fed in study 102), and mean half‐life ranged from 17 to 19 hours. Treatment‐emergent adverse events occurred in 70.8% and 83.3% subjects in studies 102 and 103, respectively, most commonly headache (41.7% and 50.0%) and gastrointestinal treatment‐emergent adverse events. The pharmacokinetics of SYM‐1219 were similar in fed and fasted states and when administered in different foods.
Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans
Authors: Nagy Christa F. , Leach Timothy S. , King Alex , Guttendorf Robert
Published: November 2017

Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high‐affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6–9 days, and terminal half‐life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection‐site abscesses or hypersensitivity reactions occurred; no subjects developed treatment‐emergent antitherapeutic antibodies over the study period of 71 days.
Bioavailability and Pharmacokinetics of TRPV1 Antagonist Mavatrep (JNJ‐39439335) Tablet and Capsule Formulations in Healthy Men: Two Open‐Label, Crossover, Single‐Dose Phase 1 Studies
Authors: Manitpisitkul Prasarn , Shalayda Kevin , Russell Lucille , Sanga Panna , Williams Yinka , Solanki Bhavna , Caruso Joseph , Moyer John A.
Published: November 2017

To improve room temperature stability and oral bioavailability of mavatrep (JNJ‐39439335, a transient receptor potential vanilloid subtype‐1 antagonist), various formulations were initially developed and evaluated in 2 phase 1 open‐label, randomized, 3‐way crossover studies in healthy participants. Study 1 evaluated 2 new overencapsulated tablet formulations (formulations B and C) relative to an overencapsulated early tablet formulation (formulation A), using mavatrep HCl salt form. Because these tablets were still not room‐temperature stable, in study 2: two free‐base solid dispersion amorphous formulations (formulations D and E) were evaluated relative to the best encapsulated formulation from study 1 (formulation C) and also food effect. Both studies had screening (∼4 weeks), treatment (study 1: n = 18, 6‐sequenced; formulations B and C [2 × 25 mg] versus A [2 × 25 mg]; study 2, part 1: n = 24, formulations D and E [2 × 12.5 mg] versus C [1 × 25 mg]; study 2, part 2: n = 16, best formulation from part 1 fed versus fasted, 2 × 12.5 mg) with a 21‐day washout period and a follow‐up. Mavatrep exhibited consistent pharmacokinetics across formulations. Following rapid absorption (median tmax, 1.5–6.5 hours), plasma concentrations declined multiexponentially (mean t1/2, 67–104 hours). The new encapsulated tablet formulation (formulation C, capsule filler: poloxamer 407) was the best formulation (Cmax and AUC values 2‐3‐fold > than the other 2) from study 1. Using this as a reference in study 2, part 1, only small (<20%) differences in mean Cmax and AUC were observed between the 3 formulations (C, D, and E). Formulation E (gelatin capsule with amorphous solid dispersion [12.5 mg free base], hydroxypropyl methylcellulose, vitamin E polyethylene glycol succinate, silicified microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide) showed improved room‐temperature stability and provided the best overall bioavailability with small variability. Small effects of a high‐fat meal on oral bioavailability were observed for formulation E, but were not clinically meaningful. Mavatrep safety profiles were similar across formulations and under fasted and fed conditions. No new safety concerns were reported.