bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Transferable Perforated Isoporous Membranes on Versatile Solid Substrates via the Breath Figure Method
Authors: Wu Lian‐Wei , Wan Ling‐Shu , Ou Yang , Zhu Liang‐Wei , Xu Zhi‐Kang
Published: August 2015

Isoporous separation membranes have received considerable attention because of the high‐resolution performance and energy‐saving characteristics. Isoporous membranes prepared by the breath figure method rely on special substrates such as water and ice because solid substrates such as polyethylene terephthalate films, which are widely used in commercial processes, often lead to nonthrough pores. In this work, it is found that highly ordered through‐pore membranes can be fabricated on hydrophilic glass surface when using polymers that are able to form ordered membranes at low concentrations. On the basis of this finding, a facile strategy is proposed to fabricate isoporous membranes on various solid substrates by introducing a water‐soluble polymer interlayer. The multifunctional interlayer promotes the spreading of membrane‐forming solutions, enables the formation of through pores, and simplifies the transfer to macroporous supports to form composite membranes. The versatility of the proposed strategy is verified by using different substrates including highly hydrophobic polytetrafluoroethylene film and using different water‐soluble polymers as the interlayer. Furthermore, the high‐resolution separation performance of the isoporous composite membranes has been demonstrated by the filtration of yeasts under gravitational pressure.
Bending Photoluminescence and Surface Photovoltaic Effect on Multilayer InSe 2D Microplate Crystals
Authors: Ho Ching‐Hwa , Chu Yun‐Ju
Published: August 2015

Recently bendable and flexible optoelectronics have attracted more attentions on display technology and concaved or curvy photovoltaic devices owing to the flexibility and softy in layered materials. The bending photoluminescence (BPL) and surface photovoltaic effect of a thin multilayer InSe 2D crystal are demonstrated here by using PL and surface photovoltage (SPV) experiments. The BPL result of InSe (t ≈ 30 nm) shows an enhancement in light intensity with respect to that of the other flat PL measurement owing to the spreading of emission solid angle for the irradiant Se‐In‐In‐Se basic units under concaved upward condition. The band edge structure of multilayer InSe is analyzed. The SPV measurement of an In mesh‐coated InSe microplate demonstrates that the Schottky‐type solar cell converts sunlight starting from ≈1 eV with the auxiliary of surface states on InSe. An initially formed In‐InSe Schottky solar cell (surface area of ≈2 mm2 and thickness of ≈85 μm) is also tested. The testing result shows a photovoltage of V ≈ 24 mV can be generated from the Schottky solar cell under the illumination of Hg lamp with power density of P ≈ 0.83 mW cm−2. All the experimental results demonstrate flexible light‐emission capability and “1 eV” photoelectric conversion capacity existed in the 2D multilayer ε‐InSe.
An accurate and inexpensive color‐based assay for detecting severe anemia in a limited‐resource setting
Authors: McGann Patrick T. , Tyburski Erika A. , de Oliveira Vysolela , Santos Brigida , Ware Russell E. , Lam Wilbur A.
Published: August 2015

Severe anemia is an important cause of morbidity and mortality among children in resource‐poor settings, but laboratory diagnostics are often limited in these locations. To address this need, we developed a simple, inexpensive, and color‐based point‐of‐care (POC) assay to detect severe anemia. The purpose of this study was to evaluate the accuracy of this novel POC assay to detect moderate and severe anemia in a limited‐resource setting. The study was a cross‐sectional study conducted on children with sickle cell anemia in Luanda, Angola. The hemoglobin concentrations obtained by the POC assay were compared to reference values measured by a calibrated automated hematology analyzer. A total of 86 samples were analyzed (mean hemoglobin concentration 6.6 g/dL). There was a strong correlation between the hemoglobin concentrations obtained by the POC assay and reference values obtained from an automated hematology analyzer (r=0.88, P<0.0001). The POC assay demonstrated excellent reproducibility (r=0.93, P<0.0001) and the reagents appeared to be durable in a tropical setting (r=0.93, P<0.0001). For the detection of severe anemia that may require blood transfusion (hemoglobin <5 g/dL), the POC assay had sensitivity of 88.9% and specificity of 98.7%. These data demonstrate that an inexpensive (<$0.25 USD) POC assay accurately estimates low hemoglobin concentrations and has the potential to become a transformational diagnostic tool for severe anemia in limited‐resource settings. Am. J. Hematol. 90:1122–1127, 2015. © 2015 Wiley Periodicals, Inc.
Regiochemistry‐Directed Syntheses of Polyhydroxylated Alkaloids from Chiral Aziridines
Authors: Eum Heesung , Choi Jihye , Cho Cheon‐Gyu , Ha Hyun‐Joon
Published: August 2015

In this study, two possible regiochemical pathways of aziridine ring opening, termed “regiochemistry‐directed branches for 2‐substituted aziridines” are described, providing easy access to two classes of compound from a common synthetic intermediate. Application of this synthetic strategy, with stereoselective dihydroxylation and reductive amination as the key steps, allowed the asymmetric synthesis of natural and unnatural polyhydroxylated alkaloids including the calyculin fragment C33–C37, 1,4‐dideoxy‐1,4‐imino‐l‐ribitol and analogues of hyacinthacine, swainsonine, castanospermine, and deoxynojirimycin. The initial domino reactions consisted of aziridine ring opening and debenzylation, and reductive double annulations were established for the preparation of bicyclic pyrrolizidine and indolizidine—represented by 8‐deoxyhyacinthacine and (3R)‐methyl‐8‐deoxyswainsonine—with remarkable stereoselectivity and in high yield.
Do “birds of a feather flock together” or do “opposites attract”? Behavioral responses and temperament predict success in pairings of rhesus monkeys in a laboratory setting
Authors: Capitanio John P. , Blozis Shelley A. , Snarr Jessica , Steward Adrianne , McCowan Brenda J.
Published: August 2015

The growing recognition that social needs of primates in captivity must be addressed can present challenges to staff at primate facilities charged with implementing pair‐housing solutions for animals. Unfortunately, there are few published papers that identify individual characteristics that might facilitate the social pairing process, and those that have looked at pre‐pairing measures of behavior have produced mixed results. Using a database of n = 340 isosexual pairing attempts, we report that measures associated with responses to a standardized infant assessment protocol (the BioBehavioral Assessment program) predict success in pairing attempts that occurred years later. Behavioral responses to a brief separation and relocation, to a human intruder challenge, as well as ratings of temperament, were obtained from rhesus monkeys at 3–4 months of age. Logistic regression was used to identify potential predictors of success when animals were paired up to 10 years after the behavioral assessments. Among females, success was higher when members of a pair were more similar (i.e., a smaller difference scores) in patterns of emotional responding (Emotionality, Nervous temperament) during the infant assessments. In contrast, among males, success was higher when the pair had lower mean values for Gentle and Nervous temperament scores; when the members were younger; when pairs had a greater weight difference; and when they came from the same rearing background. Together, our results suggest that broad measures reflecting patterns of emotionality in response to challenge, which can be assessed in infancy (but which remain relatively stable throughout life) can be usefully employed to increase the likelihood of success in pairing attempts. Am. J. Primatol. 79:e22464, 2017. © 2015 Wiley Periodicals, Inc.
Polypharmacy as a risk factor for hospital admission among ambulance‐transported old‐old patients
Authors: Abe Toshikazu , Tamiya Nanako , Kitahara Takako , Tokuda Yasuharu
Published: August 2015

Aim

The aim of this study was to analyze the relationship between polypharmacy and hospital admission in ambulance‐transported old‐old patients.

Methods

A retrospective cohort study was conducted of consecutive old‐old patients (aged ≥ 85 years) transported by ambulance to a community teaching hospital between April and December of 2013. Patients with out‐of‐hospital cardiopulmonary arrest were excluded. Data were collected from the computerized records on the demographics, chief complaints, vital signs, and level of consciousness at arrival, final diagnoses at discharge, and polypharmacy (≥5 medications). The primary outcome was requirement of hospital admission. We also analyzed symptomatic adverse drug events (ADEs).

Results

Of the 3,084 adults (aged ≥ 18 years) transported to the hospital during the study period, 381 (13%) were old‐old patients. Of those, 233 (61%) were women, and 261 (69%) were admitted to the hospital. The mean number of their baseline medications was 6.8 ± 3.9, and 250/347 patients (72%) were suffering from polypharmacy. Twenty‐seven of the patients (7%) had symptomatic ADEs. Although the ADEs were not related to polypharmacy (P = 0.437), logistic regression adjustments for age, sex, and vital signs at arrival showed that patients with polypharmacy were more likely to be admitted to the hospital than were patients without (odds ratio: 2.12 [95% CI, 1.03–4.43]; P = 0.042).

Conclusions

Symptomatic ADEs due to polypharmacy were one of the most preventable causative factors leading to hospital admission of old‐old patients. Polypharmacy could be a major risk for emergency admission to hospital.
Das erweiterte genetische Alphabet
Authors: Malyshev Denis A. , Romesberg Floyd E.
Published: August 2015

Seit dem letzten gemeinsamen Vorfahren allen Lebens auf der Erde wird die gesamte biologische Information durch ein genetisches Alphabet codiert, das aus nur vier Nucleotiden und den von ihnen gebildeten zwei Basenpaaren besteht. Aus langjährigen Versuchen, aus zwei synthetischen Nucleotiden ein drittes, nichtnatürliches Basenpaar (UBP) zu formen, haben sich jetzt drei vielversprechende Kandidaten herauskristallisiert. Eines dieser UBPs basiert auf alternativen Wasserstoffbrücken, während die beiden anderen durch hydrophobe Kräfte und Stapelkräfte stabilisiert werden. Alle drei dieser UBPs werden bemerkenswert effizient und zuverlässig repliziert und transkribiert. Die beiden letztgenannten UBP‐Typen belegen, dass nicht nur auf Basis von Wasserstoffbrücken Erbinformation gespeichert und wieder abgerufen werden kann. Dieser Aufsatz beschreibt die jüngsten Entwicklungen auf dem Gebiet der UBPs sowie ihre mögliche Anwendungen, einschließlich der Erweiterung der Evolution um den Einbau neuer Funktionalität sowie der Erschaffung semisynthetischen Lebens, das zusätzliche Information speichern kann.
Highly Efficient Enrichment of Volatile Iodine by Charged Porous Aromatic Frameworks with Three Sorption Sites
Authors: Yan Zhuojun , Yuan Ye , Tian Yuyang , Zhang Daming , Zhu Guangshan
Published: August 2015

The targeted synthesis of a series of novel charged porous aromatic frameworks (PAFs) is reported. The compounds PAF‐23, PAF‐24, and PAF‐25 are built up by a tetrahedral building unit, lithium tetrakis(4‐iodophenyl)borate (LTIPB), and different alkyne monomers as linkers by a Sonogashira–Hagihara coupling reaction. They possess excellent adsorption properties to organic molecules owing to their “breathing” dynamic frameworks. As these PAF materials assemble three effective sorption sites, namely the ion bond, phenyl ring, and triple bond together, they exhibit high affinity and capacity for iodine molecules. To the best of our knowledge, these PAF materials give the highest adsorption values among all porous materials (zeolites, metal–organic frameworks, and porous organic frameworks) reported to date.
London’sche Dispersionswechselwirkungen in der Molekülchemie – eine Neubetrachtung sterischer Effekte
Authors: Wagner J. Philipp , Schreiner Peter R.
Published: August 2015

Die London’sche Dispersion, die den attraktiven Teil des Van‐der‐Waals‐Potentials beschreibt, wurde lange als Element struktureller Stabilität in der molekularen Chemie unterschätzt. Als solches beeinflusst sie auch entscheidend die chemische Reaktivität und Katalyse. Ihre Vernachlässigung ist auf die Annahme zurückzuführen, dass die Dispersionswechselwirkung schwach sei, was nur für eine einzelne paarweise Wechselwirkung zweier Atome stimmt. Für Strukturen zunehmender Größe kann die gesamte Dispersionsstabilisierung mehrere zehn kcal mol−1 betragen. Dieser Aufsatz soll die Wichtigkeit inter‐ und intramolekularer Dispersion anhand von Beispielen für die erste Vollperiode verdeutlichen. Die Synergie aus Experiment und Theorie hat ein Niveau erreicht, auf dem Dispersionseffekte sehr genau verstanden werden können. Als Konsequenz daraus werden wir wohl unser Verständnis bezüglich sterischer Hinderung und stereoelektronischer Effekte überdenken müssen. Die Quantifizierung von Dispersionsenergiedonoren wird unsere Fähigkeiten verbessern, komplexe molekulare Strukturen und Katalysatoren zu entwickeln.
Clicked Isoreticular Metal–Organic Frameworks and Their High Performance in the Selective Capture and Separation of Large Organic Molecules
Authors: Li Pei‐Zhou , Wang Xiao‐Jun , Tan Si Yu , Ang Chung Yen , Chen Hongzhong , Liu Jia , Zou Ruqiang , Zhao Yanli
Published: August 2015

Three highly porous metal–organic frameworks (MOFs) with a uniform rht‐type topological network but hierarchical pores were successfully constructed by the assembly of triazole‐containing dendritic hexacarboxylate ligands with ZnII ions. These transparent MOF crystals present gradually increasing pore sizes upon extension of the length of the organic backbone, as clearly identified by structural analysis and gas‐adsorption experiments. The inherent accessibility of the pores to large molecules endows these materials with unique properties for the uptake of large guest molecules. The visible selective adsorption of dye molecules makes these MOFs highly promising porous materials for pore‐size‐dependent large‐molecule capture and separation.
Final‐Stage Site‐Selective Acylation for the Total Syntheses of Multifidosides A–C
Authors: Ueda Yoshihiro , Furuta Takumi , Kawabata Takeo
Published: August 2015

The first total syntheses of multifidosides A–C have been achieved. The synthetic strategy is characterized by catalytic site‐selective acylation of unprotected glycoside precursors in the final stage of the synthesis. High functional‐group tolerance of the site‐selective acylation, promoted by an organocatalyst, enabled the conventionally difficult molecular transformation in a predictable and reliable manner. An advantage of this strategy is to avoid the risks of undesired side reactions during the removal of the protecting groups at the final stage of the total synthesis.
Synthese überbrückter Diketopiperazine mit Hilfe des persistenten Radikaleffekts und eine formale Synthese von Bicyclomycin
Authors: Amatov Tynchtyk , Pohl Radek , Císařová Ivana , Jahn Ullrich
Published: August 2015

Ein konzeptionell neuer und vereinheitlichter Zugang zu vielfältigen überbrückten Diketopiperazinen (DKP) mit variabler Ringgröße wurde auf der Basis des persistenten Radikaleffekts entwickelt. Die Methode ermöglicht einen Zugang zu den Grundgerüsten überbrückter Diketopiperazinalkaloide und wurde in einer formalen Synthese des Antibiotikums Bicyclomycin angewendet.
Zum Mechanismus des Wasserstoffatomtransfers von Wasser auf den heteronuklearen Oxidcluster [Ga2Mg2O5].+: außergewöhnliche Effekte der elektronischen Struktur
Authors: Li Jilai , Zhou Shaodong , Wu Xiao‐Nan , Tang Shiya , Schlangen Maria , Schwarz Helmut
Published: August 2015

Der Mechanismus der durch den heteronuklearen Oxidcluster [Ga2Mg2O5].+ vermittelten homolytischen Spaltung der O‐H‐Bindung in Wasser wurde mittels moderner Gasphasenexperimente und quantenchemischer Rechnungen eingehend untersucht. Basierend auf den theoretischen Untersuchungen lassen sich drei Reaktionswege unterscheiden: Neben der klassischen Übertragung eines Wasserstoffatoms (hydrogen‐atom transfer, HAT) auf ein radikalisches Sauerstoffatom existieren zwei mechanistisch unterschiedliche, protonengekoppelte Elektronenübertragungen (proton‐coupled electron transfer, PCET). Nach Koordination des Wassermoleküls an ein Magnesiumatom des Clusters zeichnet sich der energetisch günstigste Reaktionsweg durch einen intramolekularen Protonentransfer auf das freie Elektronenpaar eines verbrückenden Sauerstoffatoms sowie durch eine Reorganisation der Elektronenstruktur des Clusters aus. Dabei werden zwei strukturell identische OH‐Gruppen generiert, von denen eine – in Übereinstimmung mit Isotopenmarkierungsexperimenten – im weiteren Verlauf der Reaktion abgespalten wird.
Vinylation of Unprotected Phenols Using a Biocatalytic System
Authors: Busto Eduardo , Simon Robert C. , Kroutil Wolfgang
Published: August 2015

Readily available substituted phenols were coupled with pyruvate in buffer solution under atmospheric conditions to afford the corresponding para‐vinylphenol derivatives while releasing only one molecule of CO2 and water as the by‐products. This transformation was achieved by designing a biocatalytic system that combines three biocatalytic steps, namely the CC coupling of phenol and pyruvate in the presence of ammonia, which leads to the corresponding tyrosine derivative, followed by deamination and decarboxylation. The biocatalytic transformation proceeded with high regioselectivity and afforded exclusively the desired para products. This method thus represents an environmentally friendly approach for the direct vinylation of readily available 2‐, 3‐, or 2,3‐disubstituted phenols on preparative scale (0.5 mmol) that provides vinylphenols in high yields (65–83 %).
Electrostatic Localization of RNA to Protocell Membranes by Cationic Hydrophobic Peptides
Authors: Kamat Neha P. , Tobé Sylvia , Hill Ian T. , Szostak Jack W.
Published: August 2015

Cooperative interactions between RNA and vesicle membranes on the prebiotic earth may have led to the emergence of primitive cells. The membrane surface offers a potential platform for the catalysis of reactions involving RNA, but this scenario relies upon the existence of a simple mechanism by which RNA could become associated with protocell membranes. Here, we show that electrostatic interactions provided by short, basic, amphipathic peptides can be harnessed to drive RNA binding to both zwitterionic phospholipid and anionic fatty acid membranes. We show that the association of cationic molecules with phospholipid vesicles can enhance the local positive charge on a membrane and attract RNA polynucleotides. This phenomenon can be reproduced with amphipathic peptides as short as three amino acids. Finally, we show that peptides can cross bilayer membranes to localize encapsulated RNA. This mechanism of polynucleotide confinement could have been important for primitive cellular evolution.
Ultrasmall Black Phosphorus Quantum Dots: Synthesis and Use as Photothermal Agents
Authors: Sun Zhengbo , Xie Hanhan , Tang Siying , Yu Xue‐Feng , Guo Zhinan , Shao Jundong , Zhang Han , Huang Hao , Wang Huaiyu , Chu Paul K.
Published: August 2015

Black phosphorus quantum dots (BPQDs) were synthesized using a liquid exfoliation method that combined probe sonication and bath sonication. With a lateral size of approximately 2.6 nm and a thickness of about 1.5 nm, the ultrasmall BPQDs exhibited an excellent NIR photothermal performance with a large extinction coefficient of 14.8 Lg−1 cm−1 at 808 nm, a photothermal conversion efficiency of 28.4 %, as well as good photostability. After PEG conjugation, the BPQDs showed enhanced stability in physiological medium, and there was no observable toxicity to different types of cells. NIR photoexcitation of the BPQDs in the presence of C6 and MCF7 cancer cells led to significant cell death, suggesting that the nanoparticles have large potential as photothermal agents.
1,2‐Phosphaborines: Hybrid Inorganic/Organic P–B Analogues of Benzene
Authors: Barnard Jonathan H. , Brown Paul A. , Shuford Kevin L. , Martin Caleb D.
Published: August 2015

Photolysis of the cyclic phosphine oligomer [PPh]5 in the presence of pentaarylboroles leads to the formation of 1,2‐phosphaborines by the formal insertion of a phenylphosphinidene fragment into the endocyclic CB bond. The solid‐state structure features a virtually planar central ring with bond lengths indicating significant delocalization. Appreciable ring current in the 1,2‐phosphaborine core, detected in nuclear independent chemical shift (NICS) calculations, are consistent with aromatic character. These products are the first reported 1,2‐BPC4 conjugated heterocycles and open a new avenue for BP as a valence isoelectronic substitute for CC in arene systems.
Whole‐Genome Sequencing of a Single Viral Species from a Highly Heterogeneous Sample
Authors: Han Hee‐Sun , Cantalupo Paul G. , Rotem Assaf , Cockrell Shelley K. , Carbonnaux Martial , Pipas James M. , Weitz David A.
Published: August 2015

Metagenomic studies suggest that only a small fraction of the viruses that exist in nature have been identified and studied. Characterization of unknown viral genomes is hindered by the many genomes populating any virus sample. A new method is reported that integrates drop‐based microfluidics and computational analysis to enable the purification of any single viral species from a complex mixed virus sample and the retrieval of complete genome sequences. By using this platform, the genome sequence of a 5243 bp dsDNA virus that was spiked into wastewater was retrieved with greater than 96 % sequence coverage and more than 99.8 % sequence identity. This method holds great potential for virus discovery since it allows enrichment and sequencing of previously undescribed viruses as well as known viruses.
A Reduced 2Fe2S Cluster Probe of Sulfur–Hydrogen versus Sulfur–Gold Interactions
Authors: Crouthers Danielle J. , Ding Shengda , Denny Jason A. , Bethel Ryan D. , Hsieh Chung‐Hung , Hall Michael B. , Darensbourg Marcetta Y.
Published: August 2015

The Ph3PAu+ cation, renowned as an isolobal analogue of H+, was found to serve as a proton surrogate and form a stable Au2Fe2 complex, [(μ‐SAuPPh3)2{Fe(CO)3}2], analogous to the highly reactive dihydrosulfide [(μ‐SH)2{Fe(CO)3}2]. Solid‐state X‐ray diffraction analysis found the two SAuPPh3 and SH bridges in anti configurations. VT NMR studies, supported by DFT computations, confirmed substantial barriers of approximately 25 kcal mol−1 to intramolecular interconversion between the three stereoisomers of [(μ‐SH)2{Fe(CO)3}2]. In contrast, the largely dative SAu bond in μ‐SAuPPh3 facilitates inversion at S and accounts for the facile equilibration of the SAuPPh3 units, with an energy barrier half that of the SH analogue. The reactivity of the gold‐protected sulfur atoms of [(μ‐SAuPPh3)2{Fe(CO)3}2] was accessed by release of the gold ligand with a strong acid to generate the [(μ‐SH)2{Fe(CO)3}2] precursor of the [FeFe]H2ase‐active‐site biomimetic [(μ2‐SCH2(NR)CH2S){Fe(CO)3}2].
Rare‐Earth‐Metal Nitridophosphates through High‐Pressure Metathesis
Authors: Kloß Simon David , Schnick Wolfgang
Published: August 2015

Developing a synthetic method to target an broad spectrum of unknown phases can lead to fascinating discoveries. The preparation of the first rare‐earth‐metal nitridophosphate LiNdP4N8 is reported. High‐pressure solid‐state metathesis between LiPN2 and NdF3 was employed to yield a highly crystalline product. The in situ formed LiF is believed to act both as the thermodynamic driving force and as a flux to aiding single‐crystal formation in dimensions suitable for crystal structure analysis. Magnetic properties stemming from Nd3+ ions were measured by SQUID magnetometry. LiNdP4N8 serves as a model system for the exploration of rare‐earth‐metal nitridophosphates that may even be expanded to transition metals. High‐pressure metathesis enables the systematic study of these uncharted regions of nitride‐based materials with unprecedented properties.
Self‐Assembly of α‐Helical Polypeptides Driven by Complex Coacervation
Authors: Priftis Dimitrios , Leon Lorraine , Song Ziyuan , Perry Sarah L. , Margossian Khatcher O. , Tropnikova Anna , Cheng Jianjun , Tirrell Matthew
Published: August 2015

Reported is the ability of α‐helical polypeptides to self‐assemble with oppositely‐charged polypeptides to form liquid complexes while maintaining their α‐helical secondary structure. Coupling the α‐helical polypeptide to a neutral, hydrophilic polymer and subsequent complexation enables the formation of nanoscale coacervate‐core micelles. While previous reports on polypeptide complexation demonstrated a critical dependence of the nature of the complex (liquid versus solid) on chirality, the α‐helical structure of the positively charged polypeptide prevents the formation of β‐sheets, which would otherwise drive the assembly into a solid state, thereby, enabling coacervate formation between two chiral components. The higher charge density of the assembly, a result of the folding of the α‐helical polypeptide, provides enhanced resistance to salts known to inhibit polypeptide complexation. The unique combination of properties of these materials can enhance the known potential of fluid polypeptide complexes for delivery of biologically relevant molecules.
Monitoring of Endogenous Hydrogen Sulfide in Living Cells Using Surface‐Enhanced Raman Scattering
Authors: Li Da‐Wei , Qu Lu‐Lu , Hu Kai , Long Yi‐Tao , Tian He
Published: August 2015

Hydrogen sulfide (H2S) has emerged as an important gasotransmitter in diverse physiological processes, although many aspects of its roles remain unclear, partly owing to a lack of robust analytical methods. Herein we report a novel surface‐enhanced Raman scattering (SERS) nanosensor, 4‐acetamidobenzenesulfonyl azide‐functionalized gold nanoparticles (AuNPs/4‐AA), for detecting the endogenous H2S in living cells. The detection is accomplished with SERS spectrum changes of AuNPs/4‐AA resulting from the reaction of H2S with 4‐AA on AuNPs. The SERS nanosensor exhibits high selectivity toward H2S. Furthermore, AuNPs/4‐AA responds to H2S within 1 min with a 0.1 μM level of sensitivity. In particular, our SERS method can be utilized to monitor the endogenous H2S generated in living glioma cells, demonstrating its great promise in studies of pathophysiological pathways involving H2S.
Conversion of Anthranilate Synthase into Isochorismate Synthase: Implications for the Evolution of Chorismate‐Utilizing Enzymes
Authors: Plach Maximilian G. , Löffler Patrick , Merkl Rainer , Sterner Reinhard
Published: August 2015

Chorismate‐utilizing enzymes play a vital role in the biosynthesis of metabolites in plants as well as free‐living and infectious microorganisms. Among these enzymes are the homologous primary metabolic anthranilate synthase (AS) and secondary metabolic isochorismate synthase (ICS). Both catalyze mechanistically related reactions by using ammonia and water as nucleophiles, respectively. We report that the nucleophile specificity of AS can be extended from ammonia to water by just two amino acid exchanges in a channel leading to the active site. The observed ICS/AS bifunctionality demonstrates that a secondary metabolic enzyme can readily evolve from a primary metabolic enzyme without requiring an initial gene duplication event. In a general sense, these findings add to our understanding how nature has used the structurally predetermined features of enzyme superfamilies to evolve new reactions.
Controlled Light‐Mediated Preparation of Gold Nanoparticles by a Norrish Type I Reaction of Photoactive Polymers
Authors: Mäsing Florian , Mardyukov Artur , Doerenkamp Carsten , Eckert Hellmut , Malkus Ursula , Nüsse Harald , Klingauf Jürgen , Studer Armido
Published: August 2015

Gold nanoparticles (AuNPs) are subjects of broad interest in scientific community due to their promising physicochemical properties. Herein we report the facile and controlled light‐mediated preparation of gold nanoparticles through a Norrish type I reaction of photoactive polymers. These carefully designed polymers act as reagents for the photochemical reduction of gold ions, as well as stabilizers for the in situ generated AuNPs. Manipulating the length and composition of the photoactive polymers allows for control of AuNP size. Nanoparticle diameter can be controlled from 1.5 nm to 9.6 nm.
pH‐Responsive Pharmacological Chaperones for Rescuing Mutant Glycosidases
Authors: Mena‐Barragán Teresa , Narita Aya , Matias Dino , Tiscornia Gustavo , Nanba Eiji , Ohno Kousaku , Suzuki Yoshiyuki , Higaki Katsumi , Garcia Fernández José Manuel , Ortiz Mellet Carmen
Published: August 2015

A general approach is reported for the design of small‐molecule competitive inhibitors of lysosomal glycosidases programmed to 1) promote correct folding of mutant enzymes at the endoplasmic reticulum, 2) facilitate trafficking, and 3) undergo dissociation and self‐inactivation at the lysosome. The strategy is based on the incorporation of an orthoester segment into iminosugar conjugates to switch the nature of the aglycone moiety from hydrophobic to hydrophilic in the pH 7 to pH 5 window, which has a dramatic effect on the enzyme binding affinity. As a proof of concept, new highly pH‐responsive glycomimetics targeting human glucocerebrosidase or α‐galactosidase with strong potential as pharmacological chaperones for Gaucher or Fabry disease, respectively, were developed.
Liquid‐Crystalline Mesogens Based on Cyclo[6]aramides: Distinctive Phase Transitions in Response to Macrocyclic Host–Guest Interactions
Authors: Li Xiaowei , Li Bao , Chen Long , Hu Jinchuan , Wen Chengdanyang , Zheng Qingdong , Wu Lixin , Zeng Huaqiang , Gong Bing , Yuan Lihua
Published: August 2015

Producing macrocyclic mesogens that are responsive to guest encapsulation presents a significant challenge. Cyclo[6]aramides, a type of macrocycle with a hydrogen‐bond‐constrained backbone, exhibit thermotropic lamellar, discotic nematic, hexagonal, and rectangular columnar mesophases over a considerably wide temperature range, including at room temperature. Additionally, cyclo[6]aramides show unusual mesophase transitions from lamellar to hexagonal columnar phase mediated by macrocyclic host–guest (H–G) interactions between the macrocycles and alkylammonium salts. The phase transition, triggered by an organic guest engaging in H–G interactions with a macrocyclic cavity, provides a novel strategy for manipulating the properties of liquid‐crystalline materials. The crystal structure of a homologous cyclo[6]aramide reveals a disk‐shaped, near‐planar molecular backbone that facilitates intermolecular π–π stacking and leads to columnar assembly.
Zinc‐Catalyzed Dual C–X and C–H Borylation of Aryl Halides
Authors: Bose Shubhankar Kumar , Deißenberger Andrea , Eichhorn Antonius , Steel Patrick G. , Lin Zhenyang , Marder Todd B.
Published: August 2015

A zinc‐catalyzed combined CX and CH borylation of aryl halides using B2pin2 (pin=OCMe2CMe2O) to produce the corresponding 1,2‐diborylarenes under mild conditions was developed. Catalytic CH bond activation occurs ortho to the halide groups if such a site is available or meta to the halide if the ortho position is already substituted. This method thus represents a novel use of a group XII catalyst for CH borylation. This transformation does not proceed via a free aryne intermediate, but a radical process seems to be involved.
Attachment of Norovirus to Histo Blood Group Antigens: A Cooperative Multistep Process
Authors: Mallagaray Alvaro , Lockhauserbäumer Julia , Hansman Grant , Uetrecht Charlotte , Peters Thomas
Published: August 2015

Human noroviruses recognize histo blood group antigens (HBGAs) as cellular attachment factors. Recently, it has been discovered that norovirus infection can be significantly enhanced by HBGA binding. Yet the attachment process and how it promotes host‐cell entry is only poorly understood. The binding of a norovirus protruding (P) domain of a predominant GII.4 Saga strain to HBGAs at atomic resolution was studied. So far, independent and equivalent multiple binding sites were held responsible for attachment. Using NMR experiments we show that norovirus‐HBGA binding is a cooperative multi‐step process, and native mass spectrometry reveals four instead of two HBGA binding sites per P‐dimer. An accompanying crystallographic study has disclosed four instead of two L‐fucose binding sites per P‐dimer of a related GII.10 strain1 further supporting our findings. We have uncovered a novel paradigm for norovirus‐HBGA recognition that will inspire further studies into norovirus–host interactions.
Ring Expansion of Epoxides under Brønsted Base Catalysis: Formal [3+2] Cycloaddition of β,γ‐Epoxy Esters with Imines Providing 2,4,5‐Trisubstituted 1,3‐Oxazolidines
Authors: Kondoh Azusa , Odaira Kenta , Terada Masahiro
Published: August 2015

A novel ring‐expansion reaction of epoxides under Brønsted base catalysis was developed. The formal [3+2] cycloaddition reaction of β,γ‐epoxy esters with imines proceeds in the presence of triazabicyclodecene (TBD) as a superior Brønsted base catalyst to afford 2,4,5‐trisubstituted 1,3‐oxazolidines in a highly diastereoselective manner. This reaction involves the ring opening of the epoxides with the aid of the Brønsted base catalyst to generate α,β‐unsaturated esters having an alkoxide at the allylic position, which would formally serve as a synthetic equivalent of the 1,3‐dipole, followed by a cycloaddition reaction with imines in a stepwise fashion. This methodology enables the facile synthesis of enantioenriched 1,3‐oxazolidines from easily accessible enantioenriched epoxides.
Enzymatic Prenylation and Oxime Ligation for the Synthesis of Stable and Homogeneous Protein–Drug Conjugates for Targeted Therapy
Authors: Lee Joong‐jae , Choi Hyo‐Jung , Yun Misun , Kang YingJin , Jung Ji‐Eun , Ryu Yiseul , Kim Tae Yoon , Cha Young‐je , Cho Hyun‐Soo , Min Jung‐Joon , Chung Chul‐Woong , Kim Hak‐Sung
Published: August 2015

Targeted therapy based on protein–drug conjugates has attracted significant attention owing to its high efficacy and low side effects. However, efficient and stable drug conjugation to a protein binder remains a challenge. Herein, a chemoenzymatic method to generate highly stable and homogenous drug conjugates with high efficiency is presented. The approach comprises the insertion of the CaaX sequence at the C‐terminal end of the protein binder, prenylation using farnesyltransferase, and drug conjugation through an oxime ligation reaction. MMAF and an EGFR‐specific repebody are used as the antitumor agent and protein binder, respectively. The method enables the precisely controlled synthesis of repebody–drug conjugates with high yield and homogeneity. The utility of this approach is illustrated by the notable stability of the repebody–drug conjugates in human plasma, negligible off‐target effects, and a remarkable antitumor activity in vivo. The present method can be widely used for generating highly homogeneous and stable PDCs for targeted therapy.
Self‐Assembled DNA Nanoclews for the Efficient Delivery of CRISPR–Cas9 for Genome Editing
Authors: Sun Wujin , Ji Wenyan , Hall Jordan M. , Hu Quanyin , Wang Chao , Beisel Chase L. , Gu Zhen
Published: August 2015

CRISPR–Cas9 represents a promising platform for genome editing, yet means for its safe and efficient delivery remain to be fully realized. A novel vehicle that simultaneously delivers the Cas9 protein and single guide RNA (sgRNA) is based on DNA nanoclews, yarn‐like DNA nanoparticles that are synthesized by rolling circle amplification. The biologically inspired vehicles were efficiently loaded with Cas9/sgRNA complexes and delivered the complexes to the nuclei of human cells, thus enabling targeted gene disruption while maintaining cell viability. Editing was most efficient when the DNA nanoclew sequence and the sgRNA guide sequence were partially complementary, offering a design rule for enhancing delivery. Overall, this strategy provides a versatile method that could be adapted for delivering other DNA‐binding proteins or functional nucleic acids.
Stoichiometric Sensing to Opt between Gelation and Crystallization
Authors: Vidyasagar Adiyala , Sureshan Kana M.
Published: August 2015

A new class of organogelators having a cyclohexane‐1a,3a‐diol motif capable of congealing non‐polar liquids was developed. These gelators underwent crystallization at low concentration and gelation above the critical gelation concentration (CGC) in the same solvent. The crystals and gel fibers were analyzed by single crystal XRD and PXRD respectively, which revealed their different modes of assembly. The XRD studies and thermogravimetric analysis (TGA) confirmed that the crystals contain a water of crystallization whereas the gel fibers do not. A systematic study revealed that when the concentration of the gelator exceeds that of adventitious water in the solvent, it congeals the solvent and when the concentration of the gelator is less than water, it undergoes crystallization. This unprecedented stoichiometric sensing behavior in deciding the mode of self‐assembly offers a handle to opt between mutually competing gelation and crystallization. We have confirmed that the system can be biased to congeal or crystallize by varying the amount of water.
Ruthenium(II) complexes derived from C2‐symmetric ferrocene‐based chiral bis(phosphinite) ligands: synthesis and catalytic activity towards the asymmetric reduction of acetophenones
Authors: Ak B. , Durap F. , Aydemir M. , Baysal A.
Published: August 2015

Chiral secondary alcohols are very important building blocks and valuable synthetic intermediates both in organic synthesis and in the pharmaceutical industry for producing biologically active complex molecules. A series of new chiral Ru–phosphinite complexes (1, 2, 3, 4, 5, 6, 7, 8) were prepared from chiral C2‐symmetric ferrocenyl phosphinites and corresponding chloro complex, [Ru(η6‐p‐cymene)(μ‐Cl)Cl]2. The complexes were characterized using conventional spectroscopic methods. The binuclear complexes were tested as pre‐catalysts and were found to be good pre‐catalysts for the asymmetric transfer hydrogenation of substituted acetophenones in basic 2‐propanol at 82°C, providing the corresponding optically active alcohols with almost quantitative conversion and modest to high enantioselectivities (46–97%). Amongst the all complexes, complex 6 gave the highest ee of 97% in the reduction of 2‐methoxyacetophenone to (S)‐1‐(2‐methoxyphenyl)ethanol at 82°C. Copyright © 2015 John Wiley & Sons, Ltd.
Rapid polymer fiber airbrushing: Impact of a device design on the fiber fabrication and matrix quality
Authors: Tutak Wojtek , Gelven Grant , Markle Chris , Palmer Xavier‐Lewis
Published: August 2015

Polymer fiber matrixes can be used in a variety of applications, including electronics, tissue engineering, or coatings. Polymer airbrushing (air‐blast spinning) has the potential to overcome some of the limitations of electrospinning and has the advantage of depositing nanofibers directly on various materials. The airbrushing technique has yet to be better evaluated and optimized to achieve a higher fiber reproducibility and bulk material quality. In this study, a gravity‐fed brush (commercial airbrush) and syringe‐pump‐operated brush [custom‐built airbrush (CBA)] were compared to determine the effect of the coaxial brush design on the efficacy of fiber fabrication. At comparable fiber deposition rates, gas pressures, and polymer concentrations, the CBA produced smaller and more uniform fibers with a lower average size of polymer beads. The obtained data suggest that capillary pinching was the dominant mechanism responsible for fiber formation when we used the CBA. The estimated pinching energy was lower for the CBA at the compared polymer concentrations and at a high gas pressure. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42813.
Thermoplastic polyurethanes with isosorbide chain extender
Authors: Javni Ivan , Bilić Olivera , Bilić Nikola , Petrović Zoran S. , Eastwood Eric A. , Zhang Fan , Ilavský Jan
Published: August 2015

Isosorbide, a renewable diol derived from starch, was used alone or in combination with butane diol (BD) as the chain extender in two series of thermoplastic polyurethanes (TPU) with 50 and 70% polytetramethylene ether glycol (PTMEG) soft segment concentration (SSC), respectively. In the synthesized TPUs, the hard segment composition was systematically varied in both series following BD/isosorbide molar ratios of 100 : 0; 75 : 25; 50 : 50; 25 : 75, and 0 : 100 to examine in detail the effect of chain extenders on properties of segmented polyurethane elastomers with different morphologies. We found that polyurethanes with 50% SSC were hard elastomers with Shore D hardness of around 50, which is consistent with assumed co‐continuous morphology. Polymers with 70% SSC displayed lower Shore A hardness of 74–79 (Shore D around 25) as a result of globular hard domains dispersed in the soft matrix. Insertion of isosorbide increased rigidity, melting point and glass transition temperature of hard segments and tensile strength of elastomers with 50% SSC. These effects were weaker or non‐existent in 70% SSC series due to the short hard segments and low content of isosorbide. We also found that the thermal stability was lowered by increasing isosorbide content in both series. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42830.
Increased Risk of Autism Spectrum Disorders in Children Born to Women With Systemic Lupus Erythematosus: Results From a Large Population‐Based Cohort
Authors: Vinet Évelyne , Pineau Christian A. , Clarke Ann E. , Scott Susan , Fombonne Éric , Joseph Lawrence , Platt Robert W. , Bernatsky Sasha
Published: August 2015

Objective

In utero exposure to maternal antibodies and cytokines are potential risk factors for autism spectrum disorders (ASDs). The aim of this study was to determine whether children born to mothers with systemic lupus erythematosus (SLE) have an increased risk of ASD compared to children born to mothers without SLE.

Methods

The study population was derived from the Offspring of SLE Mothers Registry (OSLER), a large population‐based cohort identified through healthcare databases in Quebec (1989–2009) comprising all women who had ≥1 hospitalization for a delivery (stillbirth or live birth) after SLE diagnosis. As general population controls, a randomly selected group of women without SLE was matched ≥4:1 to the mothers with SLE for age and year of delivery. Children born live to mothers with SLE and those born live to matched controls were identified, and a recorded diagnosis of ASD was ascertained for each child. Multivariate analyses were performed to adjust for parents’ demographic characteristics, sex, birth order of the child, maternal comorbidities, and obstetric complications.

Results

In total, 509 women with SLE had 719 children, and 5,824 matched controls had 8,493 children. Children born to women with SLE were more frequently found to have a diagnosis of ASD compared to controls (frequency of recorded ASDs 1.4% [95% confidence interval (95% CI) 0.8–2.5] versus 0.6% [95% CI 0.5–0.8]), a difference of 0.8% (95% CI 0.1–1.9). The mean age at ASD diagnosis was younger in offspring of SLE mothers (mean 3.8 years, 95% CI 1.8–5.8) compared to offspring of controls (mean 5.7 years, 95% CI 4.9–6.5). In primary multivariate analysis, SLE offspring had a substantially increased risk of ASD compared to controls (odds ratio 2.19, 95% CI 1.09–4.39).

Conclusion

Compared to children from the general population, children born to women with SLE have an increased risk of ASD, although, in absolute terms, it represents a rare outcome. These hypothesis‐generating data provide direction for additional studies of maternal autoimmunity and ASD risk.
Comparative Risk of Hospitalized Infection Associated With Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare
Authors: Yun Huifeng , Xie Fenglong , Delzell Elizabeth , Levitan Emily B. , Chen Lang , Lewis James D. , Saag Kenneth G. , Beukelman Timothy , Winthrop Kevin L. , Baddley John W. , Curtis Jeffrey R.
Published: August 2015

Objective

The risks of hospitalized infection associated with biologic agents used to treat rheumatoid arthritis (RA) are unclear. The aim of this study was to determine whether the associated risk of hospitalized infections differed between specific biologic agents used to treat RA.

Methods

In a retrospective cohort study using Medicare data from 2006–2011 for all enrolled patients with RA, new episodes of treatment with etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab, and tocilizumab were identified. Patients were required to have received another biologic agent previously and to have been continuously enrolled in Medicare medical and pharmacy plans during the baseline period and throughout followup. Followup started on the date of initiation of treatment with the new biologic agent (after previous treatment with a different biologic agent) and ended on the date of the earliest hospitalized infection, at 12 months, after an exposure gap of >30 days, or at the time of death or loss of Medicare coverage. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) for hospitalized infection, adjusting for an infection risk score and other confounders.

Results

Of 31,801 new biologic treatment episodes in patients who had previously received another biologic agent, 12.0% were with etanercept, 15.2% with adalimumab, 5.9% with certolizumab, 4.4% with golimumab, 12.4% with infliximab, 28.9% with abatacept, 14.8% with rituximab, and 6.3% with tocilizumab. During followup, we identified 2,530 hospitalized infections; incidence rates ranged from 13.1 per 100 person‐years (abatacept) to 18.7 per 100 person‐years (rituximab). After adjustment, etanercept (HR 1.24, 95% confidence interval [95% CI] 1.07–1.45), infliximab (HR 1.39, 95% CI 1.21–1.60), and rituximab (HR 1.36, 95% CI 1.21–1.53) had significantly higher HRs for hospitalized infection compared with abatacept.

Conclusion

In RA patients with prior exposure to a biologic agent, exposure to etanercept, infliximab, or rituximab was associated with a greater 1‐year risk of hospitalized infection compared with the risk associated with exposure to abatacept.
Guidance Laws With Input Constraints and Actuator Failures
Authors: Fei Liao , Haibo Ji
Published: August 2015

A novel three‐dimensional fault‐tolerant control guidance law is proposed for interception of maneuvering targets in the presence of external disturbances, actuator failures, and control input constraints. The input‐to‐state stability (ISS) method is introduced to design the fault‐tolerant control guidance law to guarantee robust tracking of a maneuvering target. Then, a saturated fault‐tolerant control guidance law is constructed using a modified saturation function to ensure the resulting control signal will never incur input constraints, and the convergence to a small neighborhood of origin is ensured in theory. Simulation results show that the presented approach is effective in achieving a successful interception against target maneuvers, external disturbances, actuator failures, and control input constraints.