bluuebunny/crossref_metadata_2025_split huggingface dataset:
β‐Amyrin synthase from Conyza blinii expressed in Saccharomyces cerevisiae
Authors: Sun Rong , Liu Shan , Tang Zi‐Zhong , Zheng Tian‐Run , Wang Tao , Chen Hui , Li Cheng‐Lei , Wu Qi 
Published: August 2017

Conyza blinii H.Lév. is a widely used medicinal herb in southwestern China. The main pharmacological components of C. blinii are a class of oleanane‐type pentacyclic triterpene glycosides known as conyzasaponins, which are thought to be synthesized from β‐amyrin. However, no genes involved in the conyzasaponin pathway have previously been identified. Here, we identify an oxidosqualene cyclase (OSC), a β‐amyrin synthase, which mediates cyclization of 2,3‐oxidosqualene to yield β‐amyrin. Ten OSC sequences were isolated from C. blinii transcript tags. Phylogenetic analysis was used to select the tag Cb18076 as the putative β‐amyrin synthase, named CbβAS. The open reading frame of CbβAS is 2286 bp and encodes 761 amino acids. Its mature protein contains the highly conserved motifs (QXXXGXW/DCTAE) of OSCs and (MWCYCR) of β‐amyrin synthases. Transcription of CbβAS was upregulated 4–24 h after treatment of the seedlings of the C. blinii cultivar with methyl jasmonate. Furthermore, expression of CbβAS in Saccharomyces cerevisiae successfully yielded β‐amyrin. The chemical structures and concentrations of β‐amyrin were confirmed by GC‐MS/MS. The target yeast ultimately produced 4.432 mg·L−1 β‐amyrin. Thus, CbβAS is an OSC involved in conyzasaponin biosynthesis.
IMRT QA using machine learning: A multi‐institutional validation
Authors: Valdes Gilmer , Chan Maria F. , Lim Seng Boh , Scheuermann Ryan , Deasy Joseph O. , Solberg Timothy D. 
Published: August 2017

AbstractPurposeTo validate a machine learning approach to Virtual intensity‐modulated radiation therapy (IMRT) quality assurance (QA) for accurately predicting gamma passing rates using different measurement approaches at different institutions.MethodsA Virtual IMRT QA framework was previously developed using a machine learning algorithm based on 498 IMRT plans, in which QA measurements were performed using diode‐array detectors and a 3%local/3 mm with 10% threshold at Institution 1. An independent set of 139 IMRT measurements from a different institution, Institution 2, with QA data based on portal dosimetry using the same gamma index, was used to test the mathematical framework. Only pixels with ≥10% of the maximum calibrated units (CU) or dose were included in the comparison. Plans were characterized by 90 different complexity metrics. A weighted poison regression with Lasso regularization was trained to predict passing rates using the complexity metrics as input.ResultsThe methodology predicted passing rates within 3% accuracy for all composite plans measured using diode‐array detectors at Institution 1, and within 3.5% for 120 of 139 plans using portal dosimetry measurements performed on a per‐beam basis at Institution 2. The remaining measurements (19) had large areas of low CU, where portal dosimetry has a larger disagreement with the calculated dose and as such, the failure was expected. These beams need further modeling in the treatment planning system to correct the under‐response in low‐dose regions. Important features selected by Lasso to predict gamma passing rates were as follows: complete irradiated area outline (CIAO), jaw position, fraction of MLC leafs with gaps smaller than 20 or 5 mm, fraction of area receiving less than 50% of the total CU, fraction of the area receiving dose from penumbra, weighted average irregularity factor, and duty cycle.ConclusionsWe have demonstrated that Virtual IMRT QA can predict passing rates using different measurement techniques and across multiple institutions. Prediction of QA passing rates can have profound implications on the current IMRT process.
Microfluidics Cell Loading‐Dock System: Ordered Cellular Array for Dynamic Lymphocyte‐Communication Study
Authors: Li Ying , Jang Joon Hee , Wang Crystal , He Bangshun , Zhang Kai , Zhang Pengchao , Vu Timothy , Qin Lidong 
Published: August 2017

AbstractIt remains a great challenge to establish a high‐throughput platform that can explore the interactions among multiple lymphocytes (>2 cells) and retrieve the interested cells for downstream analysis. This study demonstrates a microfluidics cell loading‐dock system (Cell‐Dock) to enclose multiple cells in 1D, 2D, and 3D chambers with high throughput and efficiency and single‐cell accuracy. The loading efficiencies of 95%, 85%, and 74% for one‐, three‐, and five‐cell systems are achieved, respectively. The Cell‐Dock system provides precise and dynamic cell packing models to facilitate lymphocyte‐interaction studies. The results demonstrate that individual natural killer (NK) cells may function independently rather than cooperate to lyse target cells in the defined microenvironment. Furthermore, the strong/weak NK cells are retrieved based on their on‐chip cytotoxicity and mRNA sequencing is conducted to find the possible mechanisms for “serial killing,” an important but unsolved issue. This study finds that the stronger NK cells overexpress multiple genes involved in cytotoxicity and adhesion molecules (including the well‐known ICAM1 and seldom reported B4GALT1) might play important roles in the regulation of NK cytolysis.
Lipase‐Initiated Tandem Biginelli Reactions via in situ‐Formed Acetaldehydes in One Pot: Discovery of Single‐Ring Deep Blue Luminogens
Authors: Zhang Wei , Wang Na , Yang Zeng‐Jie , Li Yan‐Rong , Yu Yuan , Pu Xue‐Mei , Yu Xiao‐Qi 
Published: August 2017

AbstractA facile approach for the synthesis of 3,4‐dihydropyrimidin‐2(1H)‐ones was developed by a tandem multi‐component reaction (MCR) in one pot. This approach involves two steps, lipase‐catalyzed in situ generation of acetaldehyde and the Biginelli reaction in turn. Several control experiments were performed using acetaldehydes directly to explore the possible mechanism of this procedure. Moreover, owing to the distinct modularity and highly efficient features of the MCR, it can assemble libraries of structurally diverse products (yields up to 98% under the optimized conditions in this paper) and provides an exceptional synthesis tool for the discovery of the minimal deep‐blue luminogen in the solid state, namely, a single ring.magnified image
Nitrile as a Versatile Directing Group for C(sp2)–H Functionalizations
Authors: Ping Yuanyuan , Wang Liping , Ding Qiuping , Peng Yiyuan 
Published: August 2017

AbstractThe one‐step direct regioselective functionaliztion of inert C(sp2)–H bonds is an efficient and sustainable methodology for the synthesis of a variety of useful natural products and pharmaceutical intermediates. A range of functional groups have been widely used as directing group for various regioselective transformations. Among these, the weakly coordinating nitrile group has attracted much attention because it is a transformable, easily installed and readily removed directing group, which can be easily converted into a number of different functional groups, such as carboxyl, carbamoyl, aminomethyl, carbonyl, and heterocyclic functionalities. This review describes recent advances in nitrile‐directed C–H functionalizations catalyzed by palladium(II), ruthenium(II), rhodium(III) and iridium(I) catalysts. The review is divided into sections related to ortho‐, meta‐, and para‐C–H bond functionalizations, which are subdivided according to reaction type (olefination, arylation, halogenation, hydroxylation and acetoxylation).magnified image
Nanoscale Morphology of Doctor Bladed versus Spin‐Coated Organic Photovoltaic Films
Authors: Pokuri Balaji Sesha Sarath , Sit Joseph , Wodo Olga , Baran Derya , Ameri Tayebeh , Brabec Christoph J. , Moule Adam J. , Ganapathysubramanian Baskar 
Published: August 2017

AbstractRecent advances in efficiency of organic photovoltaics are driven by judicious selection of processing conditions that result in a “desired” morphology. An important theme of morphology research is quantifying the effect of processing conditions on morphology and relating it to device efficiency. State‐of‐the‐art morphology quantification methods provide film‐averaged or 2D‐projected features that only indirectly correlate with performance, making causal reasoning nontrivial. Accessing the 3D distribution of material, however, provides a means of directly mapping processing to performance. In this paper, two recently developed techniques are integrated—reconstruction of 3D morphology and subsequent conversion into intuitive morphology descriptors —to comprehensively image and quantify morphology. These techniques are applied on films generated by doctor blading and spin coating, additionally investigating the effect of thermal annealing. It is found that morphology of all samples exhibits very high connectivity to electrodes. Not surprisingly, thermal annealing consistently increases the average domain size in the samples, aiding exciton generation. Furthermore, annealing also improves the balance of interfaces, enhancing exciton dissociation. A comparison of morphology descriptors impacting each stage of photophysics (exciton generation, dissociation, and charge transport) reveals that spin‐annealed sample exhibits superior morphology‐based performance indicators. This suggests substantial room for improvement of blade‐based methods (process optimization) for morphology tuning to enhance performance of large area devices.
Social Determinants of Health: A Missing Link in Emergency Medicine Training
Authors: Axelson Daniel J. , Stull Matthew J. , Coates Wendy C. 
Published: August 2017

AbstractThe health of a population depends upon several factors, including disease, public health initiatives, and the social determinants of health (SDH). These factors often converge in the emergency department (ED) where the impact of social conditions such as homelessness, low‐literacy, and poverty lead to recidivism and may contribute to provider burnout. Inclusion of SDH topics in EM residency curricula can provide needed background information and effective strategies for coping with these patients in the clinical setting. Exercises that simulate poverty, the development of and familiarity with meaningful community partnerships, and inclusion of SDH topics in standard ED conferences (e.g., mortality and morbidity conference) can promote understanding and outline a detailed plan for treating patients facing these challenges. By incorporating educational interventions aimed at identifying and intervening on issues of SDH in the ED we may be able to better serve those patients who need us the most.
First‐line treatment selection and early monitoring patterns in chronic phase‐chronic myeloid leukemia in routine clinical practice: SIMPLICITY
Authors: Goldberg Stuart L. , Cortes Jorge E. , Gambacorti‐Passerini Carlo , Hehlmann Rüdiger , Khoury H. Jean , Michallet Mauricette , Paquette Ron L. , Simonsson Bengt , Zyczynski Teresa , Foreman Aimee , Abruzzese Elisabetta , Andorsky David , Beeker Aart , Cony‐Makhoul Pascale , Hansen Richard , Lomaia Elza , Olavarria Eduardo , Mauro Michael J. 
Published: August 2017

AbstractAchieving successful outcomes in chronic phase‐chronic myeloid leukemia (CP‐CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP‐CML receiving first‐line imatinib (n = 416), dasatinib (n = 418) or nilotinib (n = 408) in the US and 6 European countries in routine clinical practice. Twelve‐month follow‐up data of 1242 prospective patients (enrolled October 01 2010‐September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib‐treated patients enrolled earlier in the study, with subsequent shift toward dasatinib‐ and nilotinib‐treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82%, and 95% of patients by 3, 6, and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P < .001) and at academic versus community practices (P = .001). Age <65 years, patients being followed at sites within Europe, those followed at academic centers and patients no longer on first‐line therapy were more likely to be monitored by 12 months. SIMPLICITY demonstrates that the NCCN and ELN recommendations on response monitoring have not been consistently translated into routine clinical practice. In the absence of appropriate monitoring practices, clinical response to TKI therapy cannot be established, any needed changes to treatment strategy will thus not be implemented, and long‐term patient outcomes are likely to be impacted.
A Formal Total Synthesis of (+)‐Frondosin A
Authors: Kwon Kuktae , Ham Jin Su , Kim Hyoun Young , Sampath Vasu , Lee Hee‐Yoon 
Published: August 2017

AbstractAn enantio‐ and stereoselective formal total synthesis of (+)‐frondosin A was accomplished through an oxidopyrylium‐ion‐mediated [5+2] cycloaddition reaction. The cycloaddition reaction provided not only an efficient way of constructing the frondosin skeleton but also facial discrimination through an ether bridge for complete control of relative stereochemistry of the substituents in frondosin A.
Deuterium‐ und tritiummarkierte Verbindungen: Anwendungen in den modernen Biowissenschaften
Authors: Atzrodt Jens , Derdau Volker , Kerr William J. , Reid Marc 
Published: August 2017

AbstractWasserstoffisotope sind einzigartige Werkzeuge zur Identifizierung und Erforschung biologischer oder chemischer Vorgänge. Wasserstoffisotopenmarkierungen erlauben den spurlosen und direkten Einbau einer zusätzlichen Masseneinheit oder eines radioaktiven Markers in ein organisches Molekül, und dies praktisch ohne Änderungen der chemischen Struktur, der physikalischen Eigenschaften oder der biologischen Aktivität. Die Verwendung von deuteriummarkierten Isotopologen zur Untersuchung der spezifischen massenspektrometrischen (MS) Muster, die von Gemischen biologisch relevanter Moleküle hervorgerufen werden, ermöglicht eine drastische Vereinfachung der Analyse. Solche Methoden ermöglichen nun tiefe Einblicke in einen großen, kontinuierlich anwachsenden Bereich von Anwendungen in den Biowissenschaften und darüber hinaus. Speziell Tritium (3H) wird zunehmend eingesetzt, insbesondere in der pharmazeutischen Wirkstoffsuche. Aufwand und Kosten der Synthese markierter Verbindungen werden durch die hohe Empfindlichkeit der Analyse und hohe Zuverlässigkeit der erhaltenen Daten mehr als ausgeglichen. In diesem Aufsatz werden Fortschritte bei der Verwendung von Wasserstoffisotopen in den Biowissenschaften beschrieben.
A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines
Authors: Schmid Steven C. , Guzei Ilia A. , Schomaker Jennifer M. 
Published: August 2017

AbstractThe reaction of rhodium‐bound carbenes with strained bicyclic methylene aziridines results in a formal [3+1] ring expansion to yield highly substituted methylene azetidines with excellent regio‐ and stereoselectivity. The reaction appears to proceed through an ylide‐type mechanism, where the unique strain and structure of the methylene aziridine promotes a ring‐opening/ring‐closing cascade that efficiently transfers chirality from substrate to product. The resultant products can be elaborated into new azetidine scaffolds containing vicinal tertiary‐quaternary and even quaternary‐quaternary stereocenters.
Determinants of the Inhibition of DprE1 and CYP2C9 by Antitubercular Thiophenes
Authors: Liu Renhe , Lyu Xiaoxuan , Batt Sarah M , Hsu Mei‐Hui , Harbut Michael B , Vilchèze Catherine , Cheng Bo , Ajayi Kehinde , Yang Baiyuan , Yang Yun , Guo Hui , Lin Changyou , Gan Fei , Wang Chen , Franzblau Scott G. , Jacobs William R. , Besra Gurdyal S. , Johnson Eric F. , Petrassi Mike , Chatterjee Arnab K. , Fütterer Klaus , Wang Feng 
Published: August 2017

AbstractMycobacterium tuberculosis (Mtb) DprE1, an essential isomerase for the biosynthesis of the mycobacterial cell wall, is a validated target for tuberculosis (TB) drug development. Here we report the X‐ray crystal structures of DprE1 and the DprE1 resistant mutant (Y314C) in complexes with TCA1 derivatives to elucidate the molecular basis of their inhibitory activities and an unconventional resistance mechanism, which enabled us to optimize the potency of the analogs. The selected lead compound showed excellent in vitro and in vivo activities, and low risk of toxicity profile except for the inhibition of CYP2C9. A crystal structure of CYP2C9 in complex with a TCA1 analog revealed the similar interaction patterns to the DprE1–TCA1 complex. Guided by the structures, an optimized molecule was generated with differential inhibitory activities against DprE1 and CYP2C9, which provides insights for development of a clinical candidate to treat TB.
Osmium‐Mediated Transformation of 4‐Thiouridine to Cytidine as Key To Study RNA Dynamics by Sequencing
Authors: Riml Christian , Amort Thomas , Rieder Dietmar , Gasser Catherina , Lusser Alexandra , Micura Ronald 
Published: August 2017

AbstractTo understand the functional roles of RNA in the cell, it is essential to elucidate the dynamics of their production, processing and decay. A recent method for assessing mRNA dynamics is metabolic labeling with 4‐thiouridine (4sU), followed by thio‐selective attachment of affinity tags. Detection of labeled transcripts by affinity purification and hybridization to microarrays or by deep sequencing then reveals RNA expression levels. Here, we present a novel sequencing method (TUC‐seq) that eliminates affinity purification and allows for direct assessment of 4sU‐labeled RNA. It employs an OsO4‐mediated transformation to convert 4sU into cytosine. We exemplify the utility of the new method for verification of endogenous 4sU in tRNAs and for the detection of pulse‐labeled mRNA of seven selected genes in mammalian cells to determine the relative abundance of the new transcripts. The results prove TUC‐seq as a straight‐forward and highly versatile method for studies of cellular RNA dynamics.
Synthesis of Bicyclo[n.1.0]alkanes by a Cobalt‐Catalyzed Multiple C(sp3)−H Activation Strategy
Authors: Zhang Zhuo‐Zhuo , Han Ye‐Qiang , Zhan Bei‐Bei , Wang Sai , Shi Bing‐Feng 
Published: August 2017

AbstractA cobalt‐catalyzed dual C(sp3)−H activation strategy has been developed and it provides a novel strategy for the synthesis of bicyclo[4.1.0]heptanes and bicyclo[3.1.0]hexanes. A key to the success of this reaction is the conformation‐induced methylene C(sp3)−H activation of the resulting cobaltabicyclo[4.n.1] intermediate. In addition, the synthesis of bicyclo[3.1.0]hexane from pivalamide, by a triple C(sp3)−H activation, has also been demonstrated.
Intracellular Delivery of Functional Native Antibodies under Hypoxic Conditions by Using a Biodegradable Silica Nanoquencher
Authors: Yuan Peiyan , Zhang Hailong , Qian Linghui , Mao Xin , Du Shubo , Yu Changmin , Peng Bo , Yao Shao Q. 
Published: August 2017

AbstractAntibodies are important biopharmaceuticals, but almost all existing antibody‐based drugs are limited to targeting antigens located at the cell exterior because of the inability of antibodies to enter the cell interior. Available methods for intracellular delivery of antibodies have major shortcomings. Herein, we report an approach to encapsulate native antibodies in a biodegradable silica nanoquencher (BS‐qNP), which could undergo efficient cellular uptake and intracellular degradation to release antibodies only under hypoxic conditions. By coating the surface of BS‐qNP with cell‐penetrating poly(disulfide)s (CPD), the delivered antibodies (or other proteins) avoided endolysosomal trapping. Doping of the silica coating with a fluorescent dye and a dark hole quencher further endowed BS‐qNP with hypoxia‐responsive fluorescence turn‐on property. Our antibody delivery system thus provides the first platform capable of stable encapsulation, efficient uptake, on‐demand antibody release, and imaging of release/cell state.
Palladium‐Catalyzed Synthesis of Heteroarene‐Fused Cyclooctatetraenes through Dehydrogenative Cyclodimerization
Authors: Fukuzumi Keita , Nishii Yuji , Miura Masahiro 
Published: August 2017

AbstractArene‐fused cyclooctatetraenes (COTs) possess unique structural and electronic properties that originate from their saddle‐shaped π‐conjugated architectures. Considerable attention has been paid to the transition‐metal‐mediated synthesis of these cyclic compounds; however, there have been limited achievements to date in the efficient construction of heteroarene‐fused COTs. In this contribution, we report a novel Pd‐catalyzed dehydrogenative cyclodimerization of biheteroarenes through four‐fold C−H activation toward the synthesis of a series of heteroarene‐fused COTs. A set of mechanistic investigations indicated the involvement of high‐valent Pd species prior to the dimerization event in the catalytic cycle. The redox behavior of the obtained COTs is also described briefly.
Preparation of a new molecularly imprinted polymer based on self‐crosslinkable cellulose acrylate in aqueous solution: A drug delivery system for furosemide
Authors: Fareghi Amir Reza , Moghadam Peyman Najafi , Khalafy Jabbar , Bahram Morteza , Moghtader Mehdi 
Published: August 2017

ABSTRACTIn the present study, a new, green, and biodegradable molecularly imprinted polymer (MIP) based on modified cellulose is introduced for the drug furosemide. First, microcrystalline cellulose was converted into cellulose acrylate (CA). Then the prepared CA underwent self‐crosslinking in the drug preassembly solution. The preassembly solution of the drug was also prepared using furosemide as the template molecule and acrylamide as the functional monomer in an aqueous medium. The results obtained from the binding and selectivity studies indicate the successful preparation of the CA‐based MIP (CA‐MIP) in aqueous solution. In the final step, an in vitro release study of furosemide from the synthesized polymers was carried out in a pH = 7.41 phosphate‐buffered saline solution at 37 °C. The drug release profiles showed that the release rate of the CA‐MIP is more controlled than that of the corresponding nonimprinted polymer, especially at the early stages of release. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45581.
Microcellular foaming of chlorosulfonated polyethylene rubber and its kaolin‐filled compounds with supercritical nitrogen
Authors: Zhang Zhen‐Xiu , Lang Xian‐Hua , Zhang Xin , Xin Zhenxiang , K Prakashan 
Published: August 2017

ABSTRACTThe microcellular foaming of vulcanizates made from chlorosulfonated polyethylene (CSM) rubber and its kaolin‐filled compounds was carried out with supercritical nitrogen. The effects of various curing times, temperatures of the vulcanizates, and kaolin filler contents in the vulcanizates on the prepared foams were studied. The foaming of the vulcanizates with various crosslinking densities revealed the critical effect the crosslinking density of the CSM matrix played on its foaming. A certain sufficient level of crosslinking density was most effective for the foaming of the matrix; a higher crosslinking density led to a decreased cell size, increased cell density, and decreased matrix expansion in the foams. The effect of the crosslinking density was due to its effect on the free volume of the elastomeric matrix, which controlled the gas diffusion from the matrix during the pressure‐release stage of the foaming operation. The incorporation of kaolin decreased the cell size and increased the cell density of the foams; the decreased free volume and the heterogeneous cell nucleation effect of the kaolin contributed to this. The tensile strength of the foams significantly improved with increasing kaolin content in the foams. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45656.