bluuebunny/crossref_metadata_2025 huggingface dataset:
In It for the Long Haul: The Cytocompatibility of Aged Graphene Oxide and Its Degradation Products
Authors: Holt Brian D. , Arnold Anne M. , Sydlik Stefanie A.
Published: November 2016

Synthetic biomaterials are poised to transform medicine; however, current synthetic options have yet to ideally recapitulate the desirable properties of native tissue. Thus, the development of new synthetic biomaterials remains an active challenge. Due to its excellent properties, including electrical conductivity, water dispersibility, and capacity for functionalization, graphene oxide (GO) holds potential for myriads of applications, including biological devices. While many studies have evaluated the compatibility of freshly prepared GO, understanding the compatibility of GO as it ages in an aqueous environment is crucial for its safe implementation in long‐term biological applications. This is a critical disconnect, as GO has been shown to undergo an autodegradation pathway in aqueous conditions, dynamically changing its composition and structure while producing degradation products. Thus, the long‐term cytocompatibility of GO is investigated by “aging” GO over time in water and accelerating aging and decomposition via sonication. While age affects the composition and size of GO, it has no effect on cellular vitality and does not alter subcellular structures or DNA melting. Overall, GO is cytocompatible throughout the process of aging, beginning to demonstrate that GO may be utilized for long‐term in vivo applications such as implanted tissue engineered scaffolds or biosensors.
Zero‐Order Antibiotic Release from Multilayer Contact Lenses: Nonuniform Drug and Diffusivity Distributions Produce Constant‐Rate Drug Delivery
Authors: Guzman Gustavo , Es‐haghi Siamak Shams , Nugay Turgut , Cakmak Mukerrem
Published: November 2016

A novel approach to zero‐order constant‐rate drug delivery from contact lenses is presented. Quasi‐Case II non‐Fickian transport is achieved by nonuniform drug and diffusivity distributions within three‐layer bimodal amphiphilic conetworks (β‐APCNs). The center layer is a highly oxygen permeable β‐APCN matrix, which contains the drug and exhibits a high drug diffusivity. The outer β‐APCN layers contain no‐drug and are loaded with vitamin E, which slows diffusion. In contrast to single‐layer neat‐polymer and vitamin E‐loaded films that display first‐order “burst” kinetics, it is demonstrated experimentally and by modeling that the combined effect of nonuniform distribution of drug loading and diffusion constants within the three‐layer lens maintains low local drug concentration at the lens–fluid interface and yields zero‐order drug delivery. The release rates of topical antibiotics provide constant‐rate therapeutic‐level delivery with appropriate oxygen permeability for at least 30 h, at which time ≈25% of the drug was released.
Toward Scalable Flexible Nanomanufacturing for Photonic Structures and Devices
Authors: Qiao Wen , Huang Wenbin , Liu Yanhua , Li Xiangmin , Chen Lin‐Sen , Tang Jian‐Xin
Published: November 2016

Continuous and scalable nanopatterning over flexible substrates is highly desirable for both commercial and scientific interests, but is difficult to realize with traditional photolithographic processes. The recent advancements in nanofabrication methodologies enable light management with photonic structures on flexible materials, providing an increasingly popular strategy to control the light harvesting in the optoelectronic devices of photovoltaics, and in organic and inorganic light‐emitting diodes. Here, the current status of nanopatterning technologies for the fabrication of optoelectronic devices is summarized. Scalable nanopatterning technologies for nanomanufacturing on flexible materials are emphasized. Critical challenges in various patterning techniques when considering the resolution, scalability, processing throughput, and the use of masks and resists are addressed. The integration of flexible nanopatterned substrates with light manipulation in organic optoelectronic devices is also discussed; this enables the control of light flux and spectra. Finally, potential development directions are highlighted.
Performance Enhancement by ZnO Nanoparticle Layer in Hybrid Ionic Transition Metal Complex‐Light‐Emitting Electrochemical Cells (iTMC‐LECs)
Authors: Marcantonio Miriam Di , Gellner Sandra , Namanga Jude Eko , Frohleiks Julia , Gerlitzki Niels , Vollkommer Frank , Bacher Gerd , Nannen Ekaterina
Published: November 2016

Light‐emitting electrochemical cells (LECs) are solution processable solid‐state light sources comprising in their simplest architecture an ionic emissive layer in between of two electrodes. Although LECs possess several advantages that make them promising candidates for future large‐area low‐cost lighting technologies, their device wall‐plug efficacies remain so far moderate on the order of a few lumens per watt. One of the reasons therefore is considered to be the charge imbalance within the device. Here, a hybrid LEC device concept is introduced, whereby an additional layer of zinc oxide (ZnO) nanoparticles at the cathode side supports electron injection into the active light‐emitting layer and boosts the performance of the Ir‐based ionic transition metal complex LEC (iTMC‐LEC). The brightness and efficacy of the devices can be increased in average by more than 70% by the implementation of the additional inorganic layer. The time to reach the maximum brightness can be reduced in average by a factor of 7, which is attributed to an improved electron/hole balance in the device due to enhanced electron injection into the active iTMC layer.
Iron‐Promoted Tandem Cyclization of 1,3‐Diynyl Chalcogen Derivatives with Diorganyl Dichalcogenides for the Synthesis of Benzo[b]furan‐Fused Selenophenes
Authors: Neto José S. S. , Iglesias Bernardo A. , Back Davi F. , Zeni Gilson
Published: November 2016

A double intramolecular 5‐endo‐dig cyclization of butyl[2‐(phenylbuta‐1,3‐diynyl)phenyl]chalcogens has been employed in a selective preparation of benzo[b]chalcogenopheno[2,3‐d]furans. Several reaction parameters were studied to determine the best reaction conditions and we observed that the reaction of butyl[2‐(phenylbuta‐1,3‐diynyl)phenyl]chalcogens (0.25 mmol) with iron(III) chloride hexahydrate (2.0 equiv.) and diorganyl diselenides (1.75 equiv.) at reflux of dichloromethane was the most appropriate to give the products in 35–89% yields. These standard reaction conditions were compatible with many functional groups in the substrates, such as methyl, chlorine, fluorine, methoxy and heteroaryl. This protocol was also efficient for diorganyl diselenides but it was ineffective with diorganyl disulfides and ditellurides. In a competition among selenium, sulfur and oxygen nucleophiles we observed that the nucleophilicity and steric effects of the competing functional groups were determinant factors for the selectivity of the cyclization. The benzo[b]chalcogenopheno[2,3‐d]furans had absorptions in the UV region (300–350 nm range) with molar absorptivity coefficient values ascribed to spin and symmetry allowed π–π* electronic transitions. An emission located in the purple region (380–440 nm range), with a Stokes shift of between 65–100 nm, is probably associated to the charge transfer character of the excited state.

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An Enantioselective Cascade Cyclopropanation Reaction Catalyzed by Rhodium(I): Asymmetric Synthesis of Vinylcyclopropanes
Authors: Torres Òscar , Roglans Anna , Pla‐Quintana Anna
Published: November 2016

N‐Tosylhydrazone‐yne‐ene substrates are satisfactorily prepared and their cyclization under rhodium catalysis is evaluated. A cascade process involving rhodium vinyl carbene formation – through carbene/alkyne metathesis – and cyclopropanation has been developed to stereoselectively afford vinylcyclopropanes.

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Piezophototronic Effect Enhanced UV/Visible Photodetector Based on ZnO/ZnSe Heterostructure Core/Shell Nanowire Array and Its Self‐Powered Performance
Authors: Yan Shuke , Rai Satish C. , Zheng Zhi , Alqarni Fahad , Bhatt Manish , Retana Michael Anthony , Zhou Weilie
Published: November 2016

To advance the photodetection capabilities of type II core/shell nanowire‐based photodetectors, ZnSe has been employed to coat on ZnO nanowire array creating a type‐II heterojunction core/shell nanowire array with additional lower indirect band gap (≈1.84 eV), via a facile two‐step process of chemical vapor deposition and pulse laser ablation. The integrated photodetector based on the ZnO/ZnSe core/shell structure is capable of detecting the entire range of the visible spectrum, from blue to red excitation source, as well as UV light. The absolute sensitivity and the percentage change in responsivity of the photodetector are enhanced by one and three orders of magnitude, respectively. The whole range visible light photodetection and enhanced photocurrent response are attributed to the unique ZnO/ZnSe energy band realignment and the piezophototronic effect. Moreover, the photodetector exhibits self‐powered photodetection behavior under UV/visible light illumination. This study grants a potential application using ZnO/ZnSe type II heterostructure core/shell nanowire array for broad band UV/visible photodetection in both powered and self‐powered circumstances.
Sulfur‐Embedded Activated Multichannel Carbon Nanofiber Composites for Long‐Life, High‐Rate Lithium–Sulfur Batteries
Authors: Lee Jun Seop , Kim Wooyoung , Jang Jyongsik , Manthiram Arumugam
Published: November 2016

Despite the 3–5 fold higher energy density than the conventional Li‐ion cells at a lower cost, commercialization of Li–S batteries is hindered by the insulating nature of sulfur and the dissolution of intermediate polysulfides (Li2S
X
, 4 < X ≤ 8) into the electrolyte. The authors demonstrate here multichannel carbon nanofibers that are composed of parallel mesoporous channels connected with micropores as sulfur containment. In addition, hydroxyl functional groups are formed on the carbon surface through a chemical activation to enhance the interaction between sulfur and carbon. In the sulfur embedded composite, the mesoporous multichannel enhances the active material utilization and sulfur loading, while the micropores act as a reaction chamber for sulfur component and trap site for polysulfide with the assistance of the functional groups. This sulfur–carbon composite electrode with 2.2 mg cm−2 sulfur displays excellent performance with high rate capability (initial capacity of 1351 mA h g−1 at C/5 rate and 847 mA h g−1 at 5C rate), maintaining 920 mA h g−1 even after 300 cycles (a decay of 0.07% per cycle). Furthermore, a stable reversible capacity of as high as ≈1100 mA h g−1 is realized with a higher sulfur loading of 4.6 mg cm−2.
Lattice‐Cell Orientation Disorder in Complex Spinel Oxides
Authors: Chen Yan , Cheng Yongqiang , Li Juchuan , Feygenson Mikhail , Heller William T. , Liang Chengdu , An Ke
Published: November 2016

Transition metal (TM) substitution has been widely applied to change complex oxides crystal structures to create high energy density electrodes materials in high performance rechargeable lithium‐ion batteries. The complex local structure in the oxides imparted by the TM arrangement often impacts their electrochemical behaviors by influencing the diffusion and intercalation of lithium. Here, a major discrepancy is demonstrated between the global and local structures of the promising high energy density and high voltage LiNi0.5Mn1.5O4 spinel cathode material that contradicts the existing structural models. A new single‐phase lattice‐cell orientation disorder model is proposed as the mechanism for the local ordering that explains how the inhomogeneous local distortions and the coherent connection give rise to the global structure in the complex oxide. Further, the single‐phase model is consistent with the electrochemical behavior observation of the materials.
Lamp Lighters and Sidewalk Smoothers: How Individual Residents Contribute to the Maintenance of the Urban Commons
Authors: T. O'Brien Daniel
Published: November 2016

Research on collective efficacy in urban neighborhoods has focused predominantly on whether a community can regulate local behavior and spaces and less on how they do so. This study pursues the latter question by examining the social regularities that create collective efficacy, measured as the behavioral composition of a neighborhood (i.e., the extent to which each individual contributes to a social regularity). This perspective is applied to the database of requests for non‐emergency government services received by Boston, MA's 311 system in 2011 (>160,000 requests). The analysis categorized custodians who have used the system to combat physical disorder in the public space (e.g., requesting graffiti removal) into two groups—“typical custodians” who have made one or two requests in a year, and “exemplars” who have made three or more. A neighborhood's collective efficacy in reporting public issues was identified through audits of sidewalk quality and streetlight outages. Analyses revealed a collaborative model of maintenance in which typical and exemplar custodians were each necessary and non‐substitutable. A second analysis found that the two types of custodian were associated with different contextual factors, articulating two different pathways from demographic and social characteristics to collective efficacy, suggesting implications for theory and practice.
Hyperinsulinemic hypoglycemia in Beckwith–Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan
Authors: Toda Naoko , Ihara Kenji , Kojima‐Ishii Kanako , Ochiai Masayuki , Ohkubo Kazuhiro , Kawamoto Yutaka , Kohno Yoshinori , Kumasaka Sakae , Kawase Akihiko , Ueno Yasuhisa , Futatani Takeshi , Miyazawa Tokuo , Nagaoki Yuko , Nakata Setsuko , Misaki Maiko , Arai Hiroko , Kawai Masahiko , Sato Maki , Yada Yukari , Takahashi Nobuhiro , Komatsu Atsushi , Maki Kanemasa , Watabe Shinichi , Sumida Yutaka , Kuwashima Makoto , Mizumoto Hiroshi , Sato Kazuo , Hara Toshiro
Published: November 2016

Beckwith–Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non‐dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.
Delineation of Ehlers–Danlos syndrome phenotype due to the c.934C>T, p.(Arg312Cys) mutation in COL1A1: Report on a three‐generation family without cardiovascular events, and literature review
Authors: Colombi Marina , Dordoni Chiara , Venturini Marina , Zanca Arianna , Calzavara‐Pinton Piergiacomo , Ritelli Marco
Published: November 2016

Classical Ehlers–Danlos syndrome (cEDS) is a rare connective tissue disorder primarily characterized by hyperextensible skin, defective wound healing, abnormal scars, easy bruising, and generalized joint hypermobility; arterial dissections are rarely observed. Mutations in COL5A1 and COL5A2 encoding type V collagen account for more than 90% of the patients so far characterized. In addition, cEDS phenotype was reported in a small number of patients carrying the c.934C>T mutation in COL1A1 that results in an uncommon substitution of a non‐glycine residue in one Gly‐Xaa‐Yaa repeat of the pro‐α1(I)‐chain p.(Arg312Cys), which leads to disturbed collagen fibrillogenesis due to delayed removal of the type I procollagen N‐propeptide. This specific mutation has been associated with propensity to arterial rupture in early adulthood; indeed, in literature the individuals harboring this mutation are also referred to as “(classic) vascular‐like” EDS patients. Herein, we describe a three‐generation cEDS family with six adults carrying the p.(Arg312Cys) substitution, which show a variable and prevalent cutaneous involvement without any major vascular event. These data, together with those available in literature, suggest that vascular events are not a diagnostic handle to differentiate patients with the p.(Arg312Cys) COL1A1 mutation from those with COL5A1 and COL5A2 defects, and highlight that during the diagnostic process the presence of at least the p.(Arg312Cys) substitution in COL1A1 should be investigated in cEDS patients without type V collagen mutations. Nevertheless, for these patients, as well as for those affected with cEDS, a periodical vascular surveillance should be carried out together with cardiovascular risk factors monitoring. © 2016 Wiley Periodicals, Inc.
Investigation of chemosensitivity during and after an acute cold
Authors: Pellegrino Robert , Walliczek‐Dworschak Ute , Winter Gudrun , Hull David , Hummel Thomas
Published: November 2016

Background

Viral rhinitis (the “common” cold) is a frequent worldwide disease. Olfactory dysfunction is one complication that arises during infection, which in most cases heals up spontaneously upon recovery, whereas in some cases it may persist as a partial or total loss of olfaction. The aim of this prospective study was to investigate the change of other chemosensory systems during a cold.

Methods

Fifty‐eight patients (age 18 to 69 years) with an acute cold were compared to a healthy control group (n = 59; age 19 to 63 years). All patients were examined on 2 occasions separated by approximately 4 weeks. Orthonasal, retronasal, gustatory, and trigeminal nasal function were investigated. Furthermore, ratings of real foods, in terms of intensity and pleasantness, were obtained.

Results

Compared to the control group, patients showed a decreased orthonasal (threshold and discrimination) and retronasal function. Furthermore, patients exhibited a decreased sensitivity to salt and a reduced ability to localize menthol, indicating a decreased taste and trigeminal function, respectively. Upon recovery from the infection, orthonasal olfactory and trigeminal sensitivity increased, whereas retronasal sensitivity showed no improvement and salt sensitivity decreased.

Conclusion

This comprehensive study provides empirical evidence that chemosensory impairment is prevalent during a cold, and additionally shows for the first time that chemosensory features associated with food consumption persist postinfection.
Nickel‐katalysierter Alkoxy‐Alkyl‐Austausch mit Alkylboranen mittels C‐O‐Aktivierung von Aryl‐ und Enolethern
Authors: Guo Lin , Liu Xiangqian , Baumann Christoph , Rueping Magnus
Published: November 2016

Eine Nickel‐katalysierte Alkylierung von polycyclischen aromatischen Methylethern sowie von Methylenolethern mit B‐Alkyl‐9‐BBN und Trialkylboranen unter Spaltung stabiler C(sp2)‐OMe‐Bindungen wird beschrieben. Charakteristisch für die Umsetzung sind das breite Substratspektrum sowie gute Chemoselektivitäten und milde Reaktionsbedingungen. Somit wird ein neuer und vielfältiger Weg zur Bildung von C(sp2)‐C(sp3)‐Bindungen erschlossen, wobei keine β‐Hydrid‐Eliminierung beobachtet wird. Weiterhin wird ein selektiver und sequentieller Alkylierungsprozess unter Spaltung inerter C‐O‐Bindungen vorgestellt, um den Vorteil der Methode zu demonstrieren.
Cage‐like Fe,Na‐Germsesquioxanes: Structure, Magnetism, and Catalytic Activity
Authors: Bilyachenko Alexey N. , Levitsky Mikhail M. , Yalymov Alexey I. , Korlyukov Alexander A. , Khrustalev Viktor N. , Vologzhanina Anna V. , Shul'pina Lidia S. , Ikonnikov Nikolay S. , Trigub Alexander E. , Dorovatovskii Pavel V. , Bantreil Xavier , Lamaty Frédéric , Long Jérôme , Larionova Joulia , Golub Igor E. , Shubina Elena S. , Shul'pin Georgiy B.
Published: November 2016

A series of four unprecedented heterometallic metallagermsesquioxanes were synthesized. Their cage‐like architectures have a unique type of molecular topology consisting of the hexairon oxo {Fe6O19} core surrounded in a triangular manner by three cyclic germoxanolates [PhGe(O)O]5. This structural organization induces antiferromagnetic interactions between the FeIII ions through the oxygen atoms. Evaluated for this first time in catalysis, these compounds showed a high catalytic activity in the oxidation of alkanes and the oxidative formation of benzamides from alcohols.
Metal‐Free Reduction of CO2 to Methoxyborane under Ambient Conditions through Borondiformate Formation
Authors: Sau Samaresh Chandra , Bhattacharjee Rameswar , Vardhanapu Pavan K. , Vijaykumar Gonela , Datta Ayan , Mandal Swadhin K.
Published: November 2016

An abnormal N‐heterocyclic carbene (aNHC) based homogeneous catalyst has been used for the reduction of carbon dioxide to methoxyborane in the presence of a range of hydroboranes under ambient conditions and resulted in the highest turnover number of 6000. A catalytically active reaction intermediate, [aNHC‐H⋅9BBN(OCOH)2] was structurally characterized and authenticated by NMR spectroscopy. A detailed mechanistic cycle of this catalytic process via borondiformate formation has been proposed from tandem experimental and computational experiments.
Long‐term records (1781–2013) of European eel (Anguilla anguilla L.) production in the Comacchio Lagoon (Italy): evaluation of local and global factors as causes of the population collapse
Authors: Aschonitis Vassilis , Castaldelli Giuseppe , Lanzoni Mattia , Rossi Remigio , Kennedy Clive , Fano Elisa Anna
Published: November 2016

Several eel species have undergone extensive declines at both local and global level. The aim of this study was to identify the reasons for the collapse of the European eel (Anguilla anguilla) stock in an important area for biodiversity conservation (Comacchio Lagoon, Italy), in order to support the development of eel conservation plans.

The records of silver eel catches from Comacchio describe the total migratory population and cover the period 1781–2013. The data are accompanied by information related to habitat loss and other local factors. The role of local factors on the decline of the local stock was investigated, while additional information from the literature was also used to discuss the effects of global factors (including glass eel harvest for aquaculture, climate–oceanographic changes, habitat loss, pollution and parasitism) on the three eel species A. anguilla, Anguilla japonica and Anguilla rostrata.

The records from Comacchio provided significant information about the effects of local factors on the local eel populations in the past. However, the current population collapse, which started in the 1970s, could not be explained by local factors.

The literature on global factors suggests that the three eel species are under combined threat from various factors. The correlations between European aquaculture production data compared with the Comacchio yields and published data from other European eel and glass eel fisheries were found to be highly significant. Aquaculture, which depends entirely on wild‐caught glass eels, seems to play a key role in the decline of natural stocks.

Conservative estimates using FAO data showed that the current numbers of glass eels needed to support aquaculture production in Europe and Asia exceeds 2 × 109 specimens. This requirement, largely supplied by A. anguilla glass eels, can explain the decline of eel populations since the glass eel trade has been expanded at an international level.

Copyright © 2016 John Wiley & Sons, Ltd.
Novel Tacrine‐Based Pyrano[3’,4’:5,6]pyrano[2,3‐b]quinolinones: Synthesis and Cholinesterase Inhibitory Activity
Authors: Hariri Roshanak , Afshar Zahra , Mahdavi Mohammad , Safavi Maliheh , Saeedi Mina , Najafi Zahra , Sabourian Reyhaneh , Karimpour‐Razkenari Elahe , Edraki Najmeh , Moghadam Farshad Homayouni , Shafiee Abbas , Khanavi Mahnaz , Akbarzadeh Tahmineh
Published: November 2016

In order to develop effective anti‐cholinesterase compounds, a novel series of pyrano[3’,4’:5,6]pyrano[2,3‐b]quinolinones were designed, synthesized, and evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). All derivatives showed very good AChE inhibitory (AChEI) activity (IC50 = 0.37–5.62 μM) compared with rivastigmine (IC50 = 11.07 μM). Among them, 11‐amino‐12‐(2,3‐dichlorophenyl)‐3‐methyl‐7,8,9,10‐tetrahydropyrano[3’,4’:5,6]pyrano[2,3‐b]quinolin‐1(12H)‐one (6f) displayed the best inhibitory activity. However, most of the synthesized compounds showed no anti‐BChE activity and compounds 6b and 6f were found to be only moderate inhibitors. The most potent anti‐AChE compound 6f had low and moderate inhibitory activity and neuroprotective effects against beta‐secretase (BACE1) and oxidative stress‐induced cell death, respectively. Also, kinetic and molecular docking studies of binding interactions elucidated that compound 6f bound to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE.
p‐Quaterphenylene as an Aggregation‐Induced Emission Fluorogen in Supramolecular Organogels and Fluorescent Sensors
Authors: Sun Yue , Wang Yi‐Xuan , Wu Mengjiao , Yuan Wei , Chen Yulan
Published: November 2016

Two dumbbell‐shaped organogelators with a p‐quaterphenylene core were synthesized, and their self‐assembly properties were investigated. These low‐molecular‐weight gelators could form self‐supporting gels in many apolar organic solvents with an H‐type aggregation form through a synergic effect of π–π stacking, intermolecular translation‐related hydrogen bonding, and van der Waals forces. In comparison to the p‐terphenylene‐cored gelator, the extended π‐conjugated segment improved the gelation efficiency significantly with enhanced gelation rate. Additionally, these p‐quaterphenylene‐centered gelators exhibited strong fluorescence emission induced by aggregation, which not only provided an in situ method to optically monitor the gelation process, but also endowed these self‐assemblies with substantial applications in sensing explosives.
A camelid nanobody against EGFR was easily obtained through refolding of inclusion body expressed in Escherichia coli
Authors: Xu Li , Song Xiaoyu , Jia Lingyun
Published: November 2016

Using anti‐EGFR (epidermal growth factor receptor) nanobody is a good choice for diagnoses and therapeutics for high EGFR expression diseases. In the present study, the percentage composition of anti‐EGFR nanobody attained 25% of the total cell protein expressed in Escherichia coli BL21 (DE3). However, almost all nanobodies were expressed as inclusion bodies. To acquire active nanobodies, a series of dilution refolding procedures were optimized after inclusion bodies were dissolved into 6 M urea and purified with immobilized metal affinity chromatography. The results showed the refolding rate of the anti‐EGFR nanobodies attained to 73%, and about 100 mg nanobodies were refolded from 1 L cells under the conditions that the initial nanobody concentration was 0.3 mg/mL, the dilution speed was 2.5 mL/Min, the dilution buffer was Tris–HCl at pH 8.0, the additives were 0.2 M Arg, 5 mM reduced glutathione (GSH), and 1 mM oxidized glutathione (GSSG). Then the activity of the refolded nanobodies was confirmed. The results showed that the refolded anti‐EGFR nanobodies, in a dose‐dependent manner, bounded to the tumor cell surface of A431 and MCF‐7 and significantly inhibited the proliferation of A431 caused by the epidermal growth factor. Our study provides a facile method to rapidly, efficiently, and massively prepare anti‐EGFR antibodies and promotes anti‐EGFR–based recognition in cancer diagnoses and therapeutics.
Is H3K4me3 instructive for transcription activation?
Authors: Howe Françoise S. , Fischl Harry , Murray Struan C. , Mellor Jane
Published: November 2016

Tri‐methylation of lysine 4 on histone H3 (H3K4me3) is a near‐universal chromatin modification at the transcription start site of active genes in eukaryotes from yeast to man and its levels reflect the amount of transcription. Because of this association, H3K4me3 is often described as an ‘activating’ histone modification and assumed to have an instructive role in the transcription of genes, but the field is lacking a conserved mechanism to support this view. The overwhelming finding from genome‐wide studies is that actually very little transcription changes upon removal of most H3K4me3 under steady‐state or dynamically changing conditions, including at mammalian CpG island promoters. Instead, rather than a major role in instructing transcription, time‐resolved experiments provide more evidence supporting the deposition of H3K4me3 into chromatin as a result of transcription, influencing processes such as memory of previous states, transcriptional consistency between cells in a population and transcription termination.
Beyond force generation: Why is a dynamic ring of FtsZ polymers essential for bacterial cytokinesis?
Authors: Coltharp Carla , Xiao Jie
Published: November 2016

We propose that the essential function of the most highly conserved protein in bacterial cytokinesis, FtsZ, is not to generate a mechanical force to drive cell division. Rather, we suggest that FtsZ acts as a signal‐processing hub to coordinate cell wall synthesis at the division septum with a diverse array of cellular processes, ensuring that the cell divides smoothly at the correct time and place, and with the correct septum morphology. Here, we explore how the polymerization properties of FtsZ, which have been widely attributed to force generation, can also be advantageous in this signal processing role. We suggest mechanisms by which FtsZ senses and integrates both mechanical and biochemical signals, and conclude by proposing experiments to investigate how FtsZ contributes to the remarkable spatial and temporal precision of bacterial cytokinesis.
Maximization of cell viability rather than biocatalyst activity improves whole‐cell ω‐oxyfunctionalization performance
Authors: Kadisch Marvin , Julsing Mattijs K. , Schrewe Manfred , Jehmlich Nico , Scheer Benjamin , von Bergen Martin , Schmid Andreas , Bühler Bruno
Published: November 2016

It is a common misconception in whole‐cell biocatalysis to refer to an enzyme as the biocatalyst, thereby neglecting the structural and metabolic framework provided by the cell. Here, the low whole‐cell biocatalyst stability, that is, the stability of specific biocatalyst activity, in a process for the terminal oxyfunctionalization of renewable fatty acid methyl esters was investigated. This reaction, which is difficult to achieve by chemical means, is catalyzed by Escherichia coli featuring the monooxygenase system AlkBGT and the uptake facilitator AlkL from Pseudomonas putida GPo1. Corresponding products, that is, terminal alcohols, aldehydes, and acids, constitute versatile bifunctional building blocks, which are of special interest for polymer synthesis. It could clearly be shown that extensive dodecanoic acid methyl ester uptake mediated by high AlkL levels leads to whole‐cell biocatalyst toxification. Thus, cell viability constitutes the primary factor limiting biocatalyst stability and, as a result, process durability. Hence, a compromise had to be found between low biocatalyst activity due to restricted substrate uptake and poor biocatalyst stability due to AlkL‐mediated toxification. This was achieved by the fine‐tuning of heterologous alkL expression, which, furthermore, enabled the identification of the alkBGT expression level as another critical factor determining biocatalyst stability. Controlled synthesis of AlkL and reduced alkBGT expression finally enabled an increase of product titers by a factor of 4.3 up to 229 g Lorg−1 in a two‐liquid phase bioprocess setup. Clearly, ω‐oxyfunctionalization process performance was determined by cell viability and thus biocatalyst stability rather than the maximally achievable specific biocatalyst activity. Biotechnol. Bioeng. 2017;114: 874–884. © 2016 Wiley Periodicals, Inc.
Elimination of the apposition in Latin anatomical terms
Authors: Neumann Paul E.
Published: November 2016

The anatomical nomenclature rules require that terms be as short and simple as possible. One common exception to that rule is Latin terms that contain two nouns in nominative case, for example, Musculus masseter and Os ischium. Although these may appear to speakers of other languages to be compound nouns, they are appositions, grammatical structures in which one noun renames, defines or describes the entity named by the other noun. More than 125 terms in Terminologia Anatomica can be simplified, without loss of clarity, by prohibiting use of more than one noun in nominative case in Latin anatomical terms (e.g., Masseter and Os ischii). Clin. Anat. 30:156–158, 2017. © 2016 Wiley Periodicals, Inc.
Oldest medical description of osteogenesis imperfecta (17th Century, France)
Authors: Charlier Philippe , Perciaccante Antonio , Bianucci Raffaella
Published: November 2016

Osteogenesis imperfecta (OI), also known as Lobstein's syndrome or Vrolik's syndrome, comprises a heterogeneous group of rare genetic connective tissue disorders. It is characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures of variable severity. Originally named “osteomalacia congenita,” the condition was first medically described in a family by Ekman in 1778. Here, we report a 17th century medical account from France, which predates Eckman's doctoral dissertation by about a century. Medical analysis of this anatomical presentation indicates a precise diagnosis of Type I OI. Clin. Anat. 30:128–129, 2017. © 2016 Wiley Periodicals, Inc.
Human anatomy nomenclature rules for the computer age
Authors: Neumann Paul E. , Baud Robert , Sprumont Pierre
Published: November 2016

Information systems are increasing in importance in biomedical sciences and medical practice. The nomenclature rules of human anatomy were reviewed for adequacy with respect to modern needs. New rules are proposed here to ensure that each Latin term is uniquely associated with an anatomical entity, as short and simple as possible, and machine‐interpretable. Observance of these recommendations will also benefit students and translators of the Latin terms into other languages. Clin. Anat. 30:300–302, 2017. © 2016 Wiley Periodicals, Inc.
A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging
Authors: Wong Pamela T. , Tang Shengzhuang , Cannon Jayme , Mukherjee Jhindan , Isham Danielle , Gam Kristina , Payne Michael , Yanik Sean A. , Baker James R. , Choi Seok Ki
Published: November 2016

Despite the immense potential of existing photocaging technology, its application is limited by the paucity of advanced caging tools. Here, we report on the design of a novel thioacetal ortho‐nitrobenzaldehyde (TNB) dual arm photocage that enabled control of the simultaneous release of two payloads linked to a single TNB unit. By using this cage, which was prepared in a single step from commercial 6‐nitroverataldehyde, three drug–fluorophore conjugates were synthesized: Taxol‐TNB‐fluorescein, Taxol‐TNB‐coumarin, and doxorubicin‐TNB‐coumarin, and long‐wavelength UVA light‐triggered release experiments demonstrated that dual payload release occurred with rapid decay kinetics for each conjugate. In cell‐based assays performed in vitro, dual release could also be controlled by UV exposure, resulting in increased cellular fluorescence and cytotoxicity with potency equal to that of unmodified drug towards the KB carcinoma cell line. The extent of such dual release was quantifiable by reporter fluorescence measured in situ and was found to correlate with the extent of cytotoxicity. Thus, this novel dual arm cage strategy provides a valuable tool that enables both active control and real‐time monitoring of drug activation at the delivery site.
An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity
Authors: Khatun Farjana , Stephenson Rachel J. , Toth Istvan
Published: November 2016

Bacterial cell‐surface‐derived or mimicked carbohydrate moieties that act as protective antigens are used in the development of antibacterial glycoconjugate vaccines. The carbohydrate antigen must have a minimum length or size to maintain the conformational structure of the antigenic epitope(s). The presence or absence of O‐acetate, phosphate, glycerol phosphate and pyruvate ketal plays a vital role in defining the immunogenicity of the carbohydrate antigen. The nature of the carrier protein, spacer and conjugation pattern used to develop the glycoconjugate vaccine also defines its overall spatial orientation which in turn affects its avidity and selectivity of interaction with the desired target(s). In addition, the ratio of carbohydrate to protein in glycoconjugate vaccines also makes an important contribution in determining the optimum immunological response. This Review article presents the importance of these variables in the development of antibacterial glycoconjugate vaccines and their effects on immune efficacy.
TiO2‐Supported Re as a General and Chemoselective Heterogeneous Catalyst for Hydrogenation of Carboxylic Acids to Alcohols
Authors: Toyao Takashi , Siddiki S. M. A. Hakim , Touchy Abeda S. , Onodera Wataru , Kon Kenichi , Morita Yoshitsugu , Kamachi Takashi , Yoshizawa Kazunari , Shimizu Ken‐ichi
Published: November 2016

TiO2‐supported Re, Re/TiO2, was found to promote selective hydrogenation of carboxylic acids having aromatic and aliphatic moieties to the corresponding alcohols. Re/TiO2 showed superior results compared to other transition‐metal‐loaded TiO2 and supported Re catalysts for selective hydrogenation of 3‐phenylpropionic acid. 3‐phenylpropanol was produced in 97 % yield under mild conditions (5 MPa H2 at 140 °C). Contrary to typical heterogeneous catalysts, Re/TiO2 does not lead to the formation of dearomatized byproducts. The catalyst is recyclable and shows a wide substrate scope in the synthesis of alcohols (22 examples; up to 97 % isolated yield).
Zur Bindung bereit: Wie der T‐Zell‐Rezeptor aktiviert wird
Authors: Tetsch Larissa
Published: November 2016

T‐Zellen gehören zur erworbenen Immunabwehr und erkennen Fremdstoffe über ihren T‐Zell‐Rezeptor. Dieser liegt, wie man seit kurzem weiß, in zwei Zuständen vor, die spontan in einander umwandelbar sind: einem ruhenden, inaktiven und einem voraktivierten Zustand. Nur voraktivierte Rezeptoren können Fremdstoffe binden und eine Immunantwort auslösen. Eine vorzeitige Aktivierung wird durch die Bindung des inaktiven Rezeptors an Membranlipide verhindert.
Wie entstanden und funktionierten die ersten Nucleinsäuren?
Authors: Groß Michael
Published: November 2016

Dass Ribonucleinsäure (RNA) in der Urzeit des Lebens auf der Erde eine zentrale Rolle spielte und sowohl als Erbmaterial als auch als Katalysator diente, ist inzwischen mit vielen Indizien belegt und weithin anerkannt, aber viele wichtige Details bleiben noch offen. Eine neue Arbeit zeigt, wie die allerersten Nucleotide das in allen Nucleinsäuren als Kettenglied vorhandene Phosphat rekrutiert haben könnten. Eine weitere demonstriert erstmals eine allein auf RNA beruhende exponentielle Vervielfältigung von RNA‐Genen und deren Umsetzung in funktionale RNA‐Moleküle.
Papierbasierte mikrofluidische Systeme
Authors: Ruffert Christine
Published: November 2016

Die Mikrofluidik ist ein interdisziplinäres Forschungsgebiet, das sich mit der Untersuchung des Strömungsverhaltens flüssiger und gasförmiger Stoffe in Systemen mit mikrometerkleinen Strukturen befasst. Einen Teilbereich der Mikrofluidik bilden papierbasierte Schnelltests. Prominente Beispiele für solche Schnelltests sind der Schwangerschaftstest und Tests zum Drogennachweis. Die in diesem Beitrag vorgestellte Lehr‐/Lerneinheit ist Teil einer Lehrveranstaltung, in der Studierende mit Konzepten der Fertigung und des Einsatzes einfacher, aus Papier bestehender Analysesysteme vertraut gemacht werden. Durch Medieneinsatz und die aktive Beteiligung des Auditoriums wird der Unterricht lernorientiert gestaltet und die Inhalte durch die Einbindung praktischer Elemente in der technischen Übung vertieft. Diese Lehr‐/Lerneinheit wurde im Rahmen der zweisemestrigen Vorlesung Mikrofluidik an der Leibniz Universität Hannover eingesetzt und ist in modifizierter Form auch für den Sekundarbereich II im Schulunterricht geeignet.
Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high‐grade, operable osteosarcomas of the extremities: A report from the Latin American Group of Osteosarcoma Treatment
Authors: Senerchia Andreza A. , Macedo Carla Renata , Ferman Sima , Scopinaro Marcelo , Cacciavillano Walter , Boldrini Erica , Lins de Moraes Vera Lúcia , Rey Guadalupe , de Oliveira Claudia T. , Castillo Luis , Almeida Maria Tereza , Borsato Maria Luisa , Lima Eduardo , Lustosa Daniel , Barreto José Henrique , El‐Jaick Tatiana , Aguiar Simone , Brunetto Algemir , Greggiani Lauro , Cogo‐Moreira Hugo , Atallah Alvaro , Petrilli Antonio Sergio
Published: November 2016

BACKGROUND

Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high‐grade operable osteosarcomas (OSTs) of the extremities was investigated.

METHODS

Patients with high‐grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event‐free survival (EFS) from randomization.

RESULTS

There were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP‐MC group and the MAP‐alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS.

CONCLUSIONS

According to the current follow‐up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high‐grade, resectable OSTs of the extremities. Cancer 2017;123:1003–10. © 2016 American Cancer Society.
Intraoperative near‐infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large‐animal model
Authors: Keating Jane J. , Runge Jeffrey J. , Singhal Sunil , Nims Sarah , Venegas Ollin , Durham Amy C. , Swain Gary , Nie Shuming , Low Philip S. , Holt David E.
Published: November 2016

BACKGROUND

Complete tumor resection is the most important predictor of patient survival with non–small cell lung cancer. Methods for intraoperative margin assessment after lung cancer excision are lacking. This study evaluated near‐infrared (NIR) intraoperative imaging with a folate‐targeted molecular contrast agent (OTL0038) for the localization of primary lung adenocarcinomas, lymph node sampling, and margin assessment.

METHODS

Ten dogs with lung cancer underwent either video‐assisted thoracoscopic surgery or open thoracotomy and tumor excision after an intravenous injection of OTL0038. Lungs were imaged with an NIR imaging device both in vivo and ex vivo. The wound bed was re‐imaged for retained fluorescence suspicious for positive tumor margins. The tumor signal‐to‐background ratio (SBR) was measured in all cases. Next, 3 human patients were enrolled in a proof‐of‐principle study. Tumor fluorescence was measured both in situ and ex vivo.

RESULTS

All canine tumors fluoresced in situ (mean Fluoptics SBR, 5.2 [range, 2.7‐8.1]; mean Karl Storz SBR 1.9 [range, 1.4‐2.6]). In addition, the fluorescence was consistent with tumor margins on pathology. Three positive lymph nodes were discovered with NIR imaging. Also, a positive retained tumor margin was discovered upon NIR imaging of the wound bed. Human pulmonary adenocarcinomas were also fluorescent both in situ and ex vivo (mean SBR, > 2.0).

CONCLUSIONS

NIR imaging can identify lung cancer in a large‐animal model. In addition, NIR imaging can discriminate lymph nodes harboring cancer cells and also bring attention to a positive tumor margin. In humans, pulmonary adenocarcinomas fluoresce after the injection of the targeted contrast agent. Cancer 2017;123:1051–60. © 2016 American Cancer Society.
Flow cytometry based rapid duplexed immunoassay for fusarium mycotoxins
Authors: Czéh Árpád , Mézes Miklós , Mandy Francis , Szőke Zsuzsanna , Nagyéri György , Laufer Noémi , Kőszegi Balázs , Koczka Tamás , Kunsági‐Máté Sándor , Lustyik György
Published: November 2016

At small food processing facilities, the most frequently used test to determine if grain‐derived mycotoxin concentrations are compliant with legal limits is the enzyme‐linked immunosorbent assay (ELISA). Each kit is designed to detect one of the six dangerous mycotoxins. With the increasing occurrence of coinfection of grain with multiple‐mycotoxins in the field and/or during storage, ELISA is no longer a cost effective best assay option. With ELISA, each species of mycotoxin requires different sample preparation/extraction and a 45 min incubation. The alternative multiplexed assay presented here, the competitive fluorescent microsphere immunoassay (CFIA), follows current food safety standards. It handles several toxins simultaneously with a single universal extraction protocol. The authors' objective was to modify an existing commercial CFIA kit developed for bench top flow cytometry and extend its utility for point‐of‐need (PON) applications. The accelerated protocol offers over 60% reduction in total processing time and it detects dual mycotoxin contamination simultaneously. The observed enhanced binding kinetics equations reported here utilizing suspended solid phase particles in liquid phase, are also supported by published theoretical calculations. In the near future portable cytometry may bring rapid multiplexed PON testing to assure the safety of small food processing installations. © 2016 International Society for Advancement of Cytometry