bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly Stable trans‐Cyclooctene Amino Acids for Live‐Cell Labeling
Authors: Hoffmann Jan‐Erik , Plass Tilman , Nikić Ivana , Aramburu Iker Valle , Koehler Christine , Gillandt Hartmut , Lemke Edward A. , Schultz Carsten 
Published: July 2015

Abstracttrans‐Cyclooctene groups incorporated into proteins via non‐canonical amino acids (ncAAs) are emerging as specific handles for bioorthogonal chemistry. Here, we present a highly improved synthetic access to the axially and the equatorially linked trans‐cyclooct‐2‐ene isomers (1 a,b). We further show that the axially connected isomer has a half‐life about 10 times higher than the equatorial isomer and reacts with tetrazines much faster, as determined by stopped‐flow experiments. The improved properties resulted in different labeling performance of the insulin receptor on the surface of intact cells.
A New Strategy for Enantioselective Construction of Multisubstituted Five‐Membered Oxygen Heterocycles via a Domino Michael/Hemiketalization Reaction
Authors: Hua Yuan‐Zhao , Liu Meng‐Meng , Huang Pei‐Jin , Song Xixi , Wang Min‐Can , Chang Jun‐Biao 
Published: July 2015

AbstractA new highly enantioselective domino Michael/hemiketalization reaction of α‐hydroxyacetophenone with β,γ‐unsaturated α‐keto esters for the synthesis of 2,2,4,5‐tetrasubstituted chiral tetrahydrofurans is reported. With 2 mol % intramolecular dinuclear zinc‐AzePhenol complex prepared in situ from the reaction of multidentate semi‐azacrown ether ligand with ZnEt2, the corresponding anti‐multisubstituted tetrahydrofuran products were obtained in up to 90 % yields, and 98 % enantiomeric excess (ee) at 0 °C for 45 min. Moreover, the products were easily converted to 2,3,5‐trisubstituted 2,3‐dihydrofurans without any loss in optical activity.
Functionalized Pentafluoroethylphosphanes
Authors: Allefeld Nadine , Neumann Beate , Stammler Hans‐Georg , Ignat'ev Nikolai , Hoge Berthold 
Published: July 2015

AbstractBis(diethylamino)pentafluoroethylphosphane represents a versatile starting material for the synthesis of functionalized pentafluoroethylphosphanes. Perfluoroalkyl substituted aminophosphanes themselves already exhibit interesting coordination properties and were treated with the catalytically relevant salts PtCl2 and PdCl2 affording trans‐[Cl2M{P(C2F5)(NEt2)2}2]. The hitherto unknown (C2F5)PBr2, accessible in good yields by treatment of C2F5P(NEt2)2 with HBr, was smoothly transformed into the corresponding phosphane, C2F5PH2, or fluoro derivative, C2F5PF2. Acidic hydrolysis of C2F5P(NEt2)2 yielded the phosphinic acid C2F5P(O)(OH)H, the anion of which was structurally characterized. The phosphinic acid smoothly adds to the carbonyl group of acetone under PC bond formation. An analogous reaction with aldehydes, for example, salicyl aldehyde, offers the possibility to generate stereocenters.
An Artificial Enzyme Made by Covalent Grafting of an FeII Complex into β‐Lactoglobulin: Molecular Chemistry, Oxidation Catalysis, and Reaction‐Intermediate Monitoring in a Protein
Authors: Buron Charlotte , Sénéchal‐David Katell , Ricoux Rémy , Le Caër Jean‐Pierre , Guérineau Vincent , Méjanelle Philippe , Guillot Régis , Herrero Christian , Mahy Jean‐Pierre , Banse Frédéric 
Published: July 2015

AbstractAn artificial metalloenzyme based on the covalent grafting of a nonheme FeII polyazadentate complex into bovine β‐lactoglobulin has been prepared and characterized by using various spectroscopic techniques. Attachment of the FeII catalyst to the protein scaffold is shown to occur specifically at Cys121. In addition, spectrophotometric titration with cyanide ions based on the spin‐state conversion of the initial high spin (S=2) FeII complex into a low spin (S=0) one allows qualitative and quantitative characterization of the metal center’s first coordination sphere. This biohybrid catalyst activates hydrogen peroxide to oxidize thioanisole into phenylmethylsulfoxide as the sole product with an enantiomeric excess of up to 20 %. Investigation of the reaction between the biohybrid system and H2O2 reveals the generation of a high spin (S=5/2) FeIII(η2‐O2) intermediate, which is proposed to be responsible for the catalytic sulfoxidation of the substrate.
A Highly Triflated Rare‐Earth Ion in [Eu(O3SCF3)8]5−
Authors: Bruns Jörn , Krüger Sascha , Adlung Matthias , Wickleder Claudia , Niehaus Oliver , Pöttgen Rainer , Klüner Thorsten , Kräuter Jessica , Wickleder Mathias S. 
Published: July 2015

AbstractThe reaction of Eu2O3 with fuming nitric acid, trifluormethanesulfonic acid, and its anhydride in torch‐sealed glass ampoules at 120 °C gave the europium compound (NO)5[Eu(O3SCF3)8] (orthorhombic, Fddd, Z=16, a=1932.69(4), b=2878.44(7), c=2955.12(7) pm, V=16439.7(7) Å3). The compound exhibits the [Eu(O3SCF3)8]5− anion showing for the first time a lanthanide ion that is exclusively coordinated by eight triflate anions. The anion has been further investigated by DFT calculations, which also allowed clear assignment of the vibrational spectra. Moreover, magnetochemical and luminescence measurements gave additional insight into the properties of this complex. The luminescence spectra revealed that the Eu3+ ions are in a pseudo D4d symmetric environment.
Structural Characterization of the Complex between Hen Egg‐White Lysozyme and ZrIV‐Substituted Keggin Polyoxometalate as Artificial Protease
Authors: Sap Annelies , De Zitter Elke , Van Meervelt Luc , Parac‐Vogt Tatjana N. 
Published: July 2015

AbstractSuccessful co‐crystallization of a noncovalent complex between hen egg‐white lysozyme (HEWL) and the monomeric ZrIV‐substituted Keggin polyoxometalate (POM) (Zr1 K1), (Et2NH2)3[Zr(PW11O39)] (1), has been achieved, and its single‐crystal X‐ray structure has been determined. The dimeric ZrIV‐substituted Keggin‐type polyoxometalate (Zr1 K2), (Et2NH2)10[Zr(PW11O39)2] (2), has been previously shown to exhibit remarkable selectivity towards HEWL hydrolysis. The reported X‐ray structure shows that the hydrolytically active ZrIV‐substituted Keggin POM exists as a monomeric species. Prior to hydrolysis, this monomer interacts with HEWL in the vicinity of the previously identified cleavage sites found at Trp28‐Val29 and Asn44‐Arg45, through water‐mediated H‐bonding and electrostatic interactions. Three binding sites are observed at the interface of the negatively charged Keggin POM and the positively charged regions of HEWL at: 1) Gly16, Tyr20, and Arg21; 2) Asn44, Arg45, and Asn46; and 3) Arg128.
Porphyrinylboranes Synthesized via Porphyrinyllithiums
Authors: Fujimoto Keisuke , Yorimitsu Hideki , Osuka Atsuhiro 
Published: July 2015

AbstractAs the most nucleophilic porphyrins, meso‐ or β‐lithiated porphyrins were generated by iodine–lithium exchange reactions of the corresponding iodoporphyrins with n‐butyllithium at −98 °C. Porphyrinyllithiums thus prepared were used for synthesis of dimesitylporphyrinylboranes through reactions with fluorodimesitylborane. The boryl groups proved to serve as an electron‐accepting unit to alter the photophysical and electrochemical properties. In addition, 5‐diarylamino‐15‐dimesitylboryl‐substituted donor–accepter porphyrins showed increased intramolecular charge‐transfer character in the S1 state. Furthermore, the reaction of β‐lithiated porphyrin with dichloromesitylborane provided a boron‐bridged porphyrin dimer, which exhibited a conjugative interaction between two porphyrin units through the vacant p‐orbital on the boron center.
Aggregation‐Induced‐Emission‐Active Macrocycle Exhibiting Analogous Triply and Singly Twisted Möbius Topologies
Authors: Wang Erjing , He Zikai , Zhao Engui , Meng Luming , Schütt Christian , Lam Jacky W. Y. , Sung Herman H. Y. , Williams Ian D. , Huang Xuhui , Herges Rainer , Tang Ben Zhong 
Published: July 2015

AbstractMolecules with Möbius topology have drawn increasing attention from scientists in a variety of fields, such as organic chemistry, inorganic chemistry, and material science. However, synthetic difficulties and the lack of functionality impede their fundamental understanding and practical applications. Here, we report the facile synthesis of an aggregation‐induced‐emission (AIE)‐active macrocycle (TPE‐ET) and investigate its analogous triply and singly twisted Möbius topologies. Because of the twisted and flexible nature of the tetraphenylethene units, the macrocycle adjusts its conformations so as to accommodate different guest molecules in its crystals. Moreover, theoretical studies including topological and electronic calculations reveal the energetically favorable interconversion process between triply and singly twisted topologies.
Source of Selectivity in Oxidative Cross‐Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3‐Hexafluoropropan‐2‐ol
Authors: Elsler Bernd , Wiebe Anton , Schollmeyer Dieter , Dyballa Katrin M. , Franke Robert , Waldvogel Siegfried R. 
Published: July 2015

AbstractInvited for the cover of this issue is the group of Siegfried R. Waldvogel at the Johannes Gutenberg‐Universität Mainz (Germany). The image depicts a monkey wrench to represent the adjustability of the oxidation potential by solvent sphere. Read the full text of the article at 10.1002/chem.201501604.
Profiling heteroscedasticity in linear regression models
Authors: Zhou Qian M. , Song Peter X.‐K. , Thompson Mary E. 
Published: July 2015

AbstractDiagnostics for heteroscedasticity in linear regression models have been intensively investigated in the literature. However, limited attention has been paid on how to identify covariates associated with heteroscedastic error variances. This problem is critical in correctly modelling the variance structure in weighted least squares estimation, which leads to improved estimation efficiency. We propose covariate‐specific statistics based on information ratios formed as comparisons between the model‐based and sandwich variance estimators. A two‐step diagnostic procedure is established, first to detect heteroscedasticity in error variances, and then to identify covariates the error variance structure might depend on. This proposed method is generalized to accommodate practical complications, such as when covariates associated with the heteroscedastic variances might not be associated with the mean structure of the response variable, or when strong correlation is present amongst covariates. The performance of the proposed method is assessed via a simulation study and is illustrated through a data analysis in which we show the importance of correct identification of covariates associated with the variance structure in estimation and inference.The Canadian Journal of Statistics43: 358–377; 2015 © 2015 Statistical Society of Canada
A phase I dose‐escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC‐223 in patients with advanced solid tumors or multiple myeloma
Authors: Bendell Johanna C. , Kelley Robin K. , Shih Kent C. , Grabowsky Jennifer A. , Bergsland Emily , Jones Suzanne , Martin Thomas , Infante Jeffrey R. , Mischel Paul S. , Matsutani Tomoo , Xu Shuichan , Wong Lilly , Liu Yong , Wu Xiaoling , Mortensen Deborah S. , Chopra Rajesh , Hege Kristen , Munster Pamela N. 
Published: July 2015

BACKGROUNDThe mammalian target of rapamycin (mTOR) pathway is essential for tumor development, yet mTOR inhibitors have yielded modest results. This phase 1 study investigated the mTORC1/mTORC2 inhibitor CC‐223 in patients with advanced cancer.METHODSPatients with advanced solid tumors or multiple myeloma received an initial dose of 7.5‐60 mg of CC‐223, followed by oral daily dosing in 28‐day cycles until disease progression. The primary objective was to determine the safety, tolerability, nontolerated dosage, maximum tolerated dosage (MTD), and preliminary pharmacokinetic profile. Secondary objectives were to evaluate pharmacodynamic effects and to describe preliminary efficacy.RESULTSTwenty‐eight patients were enrolled and received ≥1 dose of CC‐223. The most common treatment‐related grade 3 adverse events were hyperglycemia, fatigue, and rash. Four patients had dose‐limiting toxicities, including hyperglycemia, rash, fatigue, and mucositis. Therefore, 45 mg/d was determined to be the MTD. The pharmacokinetics of CC‐223 demonstrated a mean terminal half‐life ranging from 4.86 to 5.64 hours and maximum observed plasma concentration ranging from 269 to 480 ng/mL in patients who received CC‐223 ≥45 mg/d. Phosphorylation of mTORC1/mTORC2 pathway biomarkers in blood cells was inhibited by CC‐223 ≥30 mg/d with an exposure‐response relationship. Best responses included 1 partial response (breast cancer; response duration 220 days; 30‐mg/d cohort), stable disease (8 patients across ≥15 mg/d cohorts; response duration range, 36‐168 days), and progressive disease (12 patients). The disease control rate was 32%.CONCLUSIONSCC‐223 was tolerable, with manageable toxicities. Preliminary antitumor activity, including tumor regression, and evidence of mTORC1/mTORC2 pathway inhibition were observed. Cancer 2015;121:3435–43. © 2015 American Cancer Society.
Phase 1 adaptive dose‐finding study of neoadjuvant gemcitabine combined with radiation therapy for patients with high‐risk extremity and trunk soft tissue sarcoma
Authors: Tseng William W. , Zhou Shouhao , To Christina A. , Thall Peter F. , Lazar Alexander J. , Pollock Raphael E. , Lin Patrick P. , Cormier Janice N. , Lewis Valerae O. , Feig Barry W. , Hunt Kelly K. , Ballo Matthew T. , Patel Shreyaskumar , Pisters Peter W. T. 
Published: July 2015

BACKGROUNDThis study was performed to determine the maximum tolerated dose (MTD) of gemcitabine given concurrently with preoperative, fixed‐dose external‐beam radiation therapy (EBRT) for patients with resectable, high‐risk extremity and trunk soft tissue sarcoma (STS).METHODSGemcitabine was administered on days 1, 8, 22, 29, 43, and 50 with EBRT (50 Gy in 25 fractions over 5 weeks). The gemcitabine MTD was determined with a toxicity severity weight method (TSWM) incorporating 6 toxicity types. The TSWM is a Bayesian procedure that choses each cohort's dose to have a posterior mean total toxicity burden closest to a predetermined clinician‐defined target. Clinicopathologic and outcome data were also collected.RESULTSThirty‐six patients completed the study. According to the TSWM, the gemcitabine MTD was 700 mg/m2. At this dose level, 4 patients (24%) experienced grade 4 toxicity; no toxicity‐related deaths occurred. All tumors were resected with microscopically negative margins. Pathologic responses of >90% tumor necrosis were achieved in 17 patients (47%); 14 (39%) had complete responses. With a median follow‐up of 6.2 years, the 5‐year locoregional recurrence–free survival, distant metastasis–free survival, and overall survival rates were 85%, 80%, and 86%, respectively.CONCLUSIONSThe TSWM combines data from qualitatively different toxicities and can be used to determine the MTD for a drug given as part of a multimodality treatment. Neoadjuvant gemcitabine plus radiation therapy is feasible and safe in patients with high‐risk extremity and trunk STS. Major pathologic responses can be achieved, and after complete resection, long‐term clinical outcomes are encouraging. Cancer 2015;121:3659–3667. © 2015 American Cancer Society.
Everolimus combined with gefitinib in patients with metastatic castration‐resistant prostate cancer: Phase 1/2 results and signaling pathway implications
Authors: Rathkopf Dana E. , Larson Steven M. , Anand Aseem , Morris Michael J. , Slovin Susan F. , Shaffer David R. , Heller Glenn , Carver Brett , Rosen Neal , Scher Howard I. 
Published: July 2015

BACKGROUNDThe effects of mammalian target of rapamycin (mTOR) inhibition are limited by feedback reactivation of receptor tyrosine kinase signaling in phosphatase and tensin homolog–null tumors. Thus, this study tested the combination of mTOR inhibition (everolimus) and epidermal growth factor receptor inhibition (gefitinib) in castration‐resistant prostate cancer (CRPC).METHODSIn phase 1, 12 patients (10 with CRPC and 2 with glioblastoma) received daily gefitinib (250 mg) with weekly everolimus (30, 50, or 70 mg). In phase 2, 27 CRPC patients received gefitinib with everolimus (70 mg).RESULTSPhase 1 revealed no pharmacokinetic interactions and no dose‐limiting toxicities. In phase 2, 18 of 27 patients (67%) discontinued treatment before the 12‐week evaluation because of progression as evidenced by prostate‐specific antigen (PSA) levels (n = 6) or imaging (n = 5) or because of a grade 2 or higher toxicity (n = 7). Thirteen of the 37 CRPC patients (35%) exhibited a rapidly rising PSA level after they had begun treatment, and this declined upon discontinuation. Fluorodeoxyglucose positron emission tomography 24 to 72 hours after the initiation of treatment showed a decrease in the standardized uptake value consistent with mTOR inhibition in 27 of the 33 evaluable patients (82%); there was a corresponding rise in PSA in 20 of these 27 patients (74%).CONCLUSIONSThe combination of gefitinib and everolimus did not result in significant antitumor activity. The induction of PSA in tumors treated with mTOR inhibitors was consistent with preclinical data showing that phosphoinositide 3‐kinase (PI3K) pathway signaling feedback inhibits the androgen receptor (AR). This clinical evidence of relief of feedback inhibition promoting enhanced AR activity supports future studies combining PI3K pathway inhibitors and second‐generation AR inhibitors in CRPC. Cancer 2015;121:3853–3861. © 2015 American Cancer Society.
Performance analysis of distributed symmetric sparse matrix vector multiplication algorithm for multi‐core architectures
Authors: Oryspayev Dossay , Aktulga Hasan Metin , Sosonkina Masha , Maris Pieter , Vary James P. 
Published: July 2015

SummarySparse matrix vector multiply (SpMVM) is an important kernel that frequently arises in high performance computing applications. Due to its low arithmetic intensity, several approaches have been proposed in literature to improve its scalability and efficiency in large scale computations. In this paper, our target systems are high end multi‐core architectures and we use messaging passing interface + open multiprocessing hybrid programming model for parallelism. We analyze the performance of recently proposed implementation of the distributed symmetric SpMVM, originally developed for large sparse symmetric matrices arising in ab initio nuclear structure calculations. We study important features of this implementation and compare with previously reported implementations that do not exploit underlying symmetry. Our SpMVM implementations leverage the hybrid paradigm to efficiently overlap expensive communications with computations. Our main comparison criterion is the ‘CPU core hours’ metric, which is the main measure of resource usage on supercomputers. We analyze the effects of topology‐aware mapping heuristic using simplified network load model. We have tested the different SpMVM implementations on two large clusters with 3D Torus and Dragonfly topology. Our results show that the distributed SpMVM implementation that exploits matrix symmetry and hides communication yields the best value for the ‘CPU core hours’ metric and significantly reduces data movement overheads. Copyright © 2015 John Wiley & Sons, Ltd.
The σ‐Hole Interaction Between Sulfur Hexafluoride and Ammonia Characterised by Broadband Rotational Spectroscopy
Authors: Bittner Dror M. , Zaleski Daniel P. , Stephens Susanna L. , Walker Nicholas R. , Legon Anthony C. 
Published: July 2015

AbstractA weakly‐bound complex of SF6 and NH3 is generated within an expanding gas jet and characterised by broadband rotational spectroscopy. The spectra of isotopologues 32SF6⋅⋅⋅14NH3, 32SF6⋅⋅⋅14ND3, 32SF6⋅⋅⋅15NH3 and 34SF6⋅⋅⋅15NH3 are observed and assigned to determine the spectroscopic parameters. These parameters are consistent with the complex having a C3v symmetric rotor geometry, in which the nitrogen atom of NH3 coordinates to SF6 such that the C3v axis of the NH3 sub‐unit is aligned with a local C3 axis on the SF6 sub‐unit. The geometry of the complex is rationalized in terms of a σ‐hole interaction. The observed spectra and ab initio calculations also reveal evidence of internal dynamics involving internal rotation of one monomer sub‐unit with respect to the other about the symmetry axis of the complex.
An extended discrete autoregressive model for variable bit rate video traffic encoded by scalable video codec
Authors: Ahmadpour Sima , Toghrayee Zohreh , Wan Tat‐Chee 
Published: July 2015

SummaryDesigning an effective and high performance network requires accurate characterization and modeling of network traffic. This paper provides a study of the transmission, modeling, and analysis of variable bit rate (VBR) video, which is fundamental for designing protocols and for effective utilization of networks in video transmission. To meet the specified requirements of future networks, the scalable video codec (SVC) was chosen as the video compression standard. The main objective of this work was to propose a statistical model that will allow better coordination between generated SVC video traffic and original video traffic. The performance of the proposed model was evaluated by comparing the model with three existing low‐complex statistical models using graphical and statistical measurements as well as cross‐validation. For all evaluation techniques, the accuracy of the proposed model was evaluated, and the frame size distribution of the modeled traffic was found to match that of the original video traffic better than other existing models. Copyright © 2015 John Wiley & Sons, Ltd.
Morphologic analysis of false negative SurePath® slides using Focalpoint™ GS computer‐assisted cervical screening technology: An Australian experience
Authors: Bowditch Ron C. , Clarke Joanne M. , Baird Phillip J. , Greenberg Merle L. 
Published: July 2015

BackgroundThe trial results of BD FocalPoint™ GS computer assisted screening(FP) of BD SurePath® liquid based cervical cytology slides (SP) were published in Diagnostic Cytopathology in 2012.1MethodThe FP‐reviewed SP slides were compared to conventional cervical Pap smears (CON) in a split sample of 2198 routine specimens. In all 47 confirmed high grade (HG) cases, FP either selected fields of view (FOV) containing cells suspicious or diagnostic of HG (46/47), or prompted full screening of the slide (1/47) leading to detection of the HG lesion. In this study for the HG cases which were reported initially as negative (NEG) or low grade (LG), the original slides were reviewed to determine the reasons for the false negative reporting and to identify features characteristic of a HG pattern.ResultsIndicators of a high risk pattern for HG Squamous Intraepithelial lesions (HSIL) included the recognition of pale abnormal immature metaplastic cells. Indicators of a high risk pattern for HG Glandular Intraepithelial lesion (AIS) were single columnar cells with the nucleus occupying the widest area of the cell. Pavemented sheets of glandular cells and isolated mitoses were additional clues to the diagnosis. In endocervical and endometrial adenocarcinomas tumour diathesis tends to be absent in SurePath slides. Single cells with ingested neutrophils and obscured eccentric nuclei were another clue to the detection of endometrial adenocarcinoma.ConclusionThese morphological features are illustrated to help identify HSIL and HG glandular lesions when viewing the FOV presented by the FocalPointTM GS technology. Diagn. Cytopathol. 2015;43:870–878. © 2015 Wiley Periodicals, Inc.