bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amine Transaminase Engineering for Spatially Bulky Substrate Acceptance
Authors: Weiß Martin S. , Pavlidis Ioannis V. , Spurr Paul , Hanlon Steven P. , Wirz Beat , Iding Hans , Bornscheuer Uwe T. 
Published: March 2017

AbstractAmine transaminase (ATA) catalyzing stereoselective amination of prochiral ketones is an attractive alternative to transition metal catalysis. As wild‐type ATAs do not accept sterically hindered ketones, efforts to widen the substrate scope to more challenging targets are of general interest. We recently designed ATAs to accept aromatic and thus planar bulky amines, with a sequence‐based motif that supports the identification of novel enzymes. However, these variants were not active against 2,2‐dimethyl‐1‐phenyl‐propan‐1‐one, which carries a bulky tert‐butyl substituent adjacent to the carbonyl function. Here, we report a solution for this type of substrate. The evolved ATAs perform asymmetric synthesis of the respective R amine with high conversions by using either alanine or isopropylamine as amine donor.
Staged management of giant bilateral perinephric adipocytic neoplasms
Authors: Arriola Aileen Grace P. , Bartlett Edmund K. , Zhang Paul J. , Cooper Kumarasen , Naji Ali , Roses Robert E. 
Published: March 2017

Key Clinical MessageWe present a patient with giant bilateral perinephric masses favored to represent liposarcoma preoperatively. Bilateral renal involvement posed a clinical challenge; careful histologic assessment and surgical planning allowed preservation of renal function.
FMR1 premutation with Prader–Willi phenotype and fragile X‐associated tremor/ataxia syndrome
Authors: Martínez‐Cerdeño Verónica , Lechpammer Mirna , Noctor Stephen , Ariza Jeanelle , Hagerman Paul , Hagerman Randi 
Published: March 2017

Key Clinical MessageThis is a report of FMR1 premutation with Prader–Willi phenotype (PWP) and FXTAS. Although the PWP is common in fragile X syndrome (FXS), it has never been described in someone with the premutation. The patient presented intranuclear inclusions, severe obesity, hyperphagia, and ADHD symptoms, typical of the PWP in FXS. In addition, the autopsy revealed multiple architectural cortical abnormalities.
Peptide‐FlgA3‐Based Gold Palladium Bimetallic Nanoparticles That Catalyze the Oxygen Reduction Reaction in Alkaline Solution
Authors: Li Dongliang , Tang Zhenghua , Chen Shaowei , Tian Yong , Wang Xiufang 
Published: March 2017

AbstractGiven the synergetic properties of different metal species, bimetallic nanoparticles are of immense scientific interest and technological importance in the field of catalysis. A peptide‐based method represents a new avenue to fabricate bimetallic nanocatalysts with a controllable size, shape, composition, and subtle surface microstructure. However, the electrocatalytic abilities of these peptide‐based bimetallic nanoparticles remain largely unexplored. Herein, we employed the peptide sequence FlgA3 to fabricate a series of AuPd alloys that were used as catalysts for the oxygen reduction reaction (ORR). Among the samples tested, Au33Pd67 exhibited the best activity, evidenced by the most positive onset potential and the largest diffusion‐limited current. Notably, the ORR activity of Au33Pd67 was comparable with that of commercial Pt/C, and the long‐term durability was significantly superior to that of Pt/C. A peptide‐enabled approach might pave the way for the fabrication of bimetallic nanomaterials with enhanced electrocatalytic properties under mild conditions.
Role of Composition and Size of Cobalt Ferrite Nanocrystals in the Oxygen Evolution Reaction
Authors: Chakrapani Kalapu , Bendt Georg , Hajiyani Hamidreza , Schwarzrock Ingo , Lunkenbein Thomas , Salamon Soma , Landers Joachim , Wende Heiko , Schlögl Robert , Pentcheva Rossitza , Behrens Malte , Schulz Stephan 
Published: March 2017

AbstractSub‐10 nm CoFe2O4 nanoparticles with different sizes and various compositions obtained by (partial) substitution of Co with Ni cations have been synthesized by using a one‐pot method from organic solutions by the decomposition of metal acetylacetonates in the presence of oleylamine. The electrocatalytic activity of CoFe2O4 towards the oxygen evolution reaction (OER) is clearly enhanced with a smaller size (3.1 nm) of the CoFe2O4 nanoparticles (compared with 4.5 and 5.9 nm). In addition, the catalytic activity is improved by partial substitution of Co with Ni, which also leads to a higher degree of inversion of the spinel structure. Theoretical calculations attribute the positive catalytic effect of Ni owing to the lower binding energy differences between adsorbed O and OH compared with pure cobalt or nickel ferrites, resulting in higher OER activity. Co0.5Ni0.5Fe2O4 exhibited a low overpotential of approximately 340 mV at 10 mA cm−2, a smaller Tafel slope of 51 mV dec−1, and stability over 30 h. The unique tunability of these CoFe2O4 nanocrystals provides great potential for their application as an efficient and competitive anode material in the field of electrochemical water splitting as well as for systematic fundamental studies aiming at understanding the correlation of composition and structure with performance in electrocatalysis.
Highly Active Gold and Gold–Palladium Catalysts Prepared by Colloidal Methods in the Absence of Polymer Stabilizers
Authors: Abis Laura , Freakley Simon J. , Dodekatos Georgios , Morgan David J. , Sankar Meenakshisundaram , Dimitratos Nikolaos , He Qian , Kiely Christopher J. , Hutchings Graham J. 
Published: March 2017

AbstractSupported gold and gold–palladium nanoparticles were found to be effective catalysts for the selective oxidation of glycerol and benzyl alcohol. The properties and stabilities of catalysts are often sensitive to factors such as the dimensions, shape, and composition of the metal nanoparticles. Although colloidal methods provide an easy and quick way to synthesize supported metal catalysts, they typically involve the use of polymers such as polyvinyl alcohol and polyvinylpyrrolidone as steric stabilizers, which can sometimes be detrimental in subsequent catalytic reactions. Herein, we report the synthesis of supported gold and gold–palladium nanoparticles without the addition of stabilizing polymers. The catalysts prepared with and without the addition of polymers performed very similarly in the selective oxidation of glycerol and benzyl alcohol, which suggests that polymers are not essential to make active catalysts for these reactions. Thus, this new stabilizer‐free method provides a facile and highly effective way of circumventing the inherent problems of polymer stabilizers in the preparation of gold and gold–palladium catalysts.
Cobalt‐Porphyrin‐Catalysed Intramolecular Ring‐Closing C−H Amination of Aliphatic Azides: A Nitrene‐Radical Approach to Saturated Heterocycles
Authors: Kuijpers Petrus F. , Tiekink Martijn J. , Breukelaar Willem B. , Broere Daniël L. J. , van Leest Nicolaas P. , van der Vlugt Jarl Ivar , Reek Joost N. H. , de Bruin Bas 
Published: March 2017

AbstractCobalt‐porphyrin‐catalysed intramolecular ring‐closing C−H bond amination enables direct synthesis of various N‐heterocycles from aliphatic azides. Pyrrolidines, oxazolidines, imidazolidines, isoindolines and tetrahydroisoquinoline can be obtained in good to excellent yields in a single reaction step with an air‐ and moisture‐stable catalyst. Kinetic studies of the reaction in combination with DFT calculations reveal a metallo‐radical‐type mechanism involving rate‐limiting azide activation to form the key cobalt(III)‐nitrene radical intermediate. A subsequent low barrier intramolecular hydrogen‐atom transfer from a benzylic C−H bond to the nitrene‐radical intermediate followed by a radical rebound step leads to formation of the desired N‐heterocyclic ring products. Kinetic isotope competition experiments are in agreement with a radical‐type C−H bond‐activation step (intramolecular KIE=7), which occurs after the rate‐limiting azide activation step. The use of di‐tert‐butyldicarbonate (Boc2O) significantly enhances the reaction rate by preventing competitive binding of the formed amine product. Under these conditions, the reaction shows clean first‐order kinetics in both the [catalyst] and the [azide substrate], and is zero‐order in [Boc2O]. Modest enantioselectivities (29–46 % ee in the temperature range of 100–80 °C) could be achieved in the ring closure of (4‐azidobutyl)benzene using a new chiral cobalt‐porphyrin catalyst equipped with four (1S)‐(−)‐camphanic‐ester groups.
Revealing the Origin of the Efficiency of the De Novo Designed Kemp Eliminase HG‐3.17 by Comparison with the Former Developed HG‐3
Authors: Świderek Katarzyna , Tuñón Iñaki , Moliner Vicent , Bertran Joan 
Published: March 2017

AbstractThe design of new biocatalysts is a goal in biotechnology to improve the rate, selectivity and environmental impact of industrial chemical processes. In this regard, the use of computational techniques has provided valuable assistance in the design of new enzymes with remarkable catalytic activity. In this paper, hybrid QM/MM molecular dynamics simulations have allowed insights to be gained on the origin of the limited efficiency of a computationally designed enzyme for the Kemp elimination; the HG‐3. Comparison of results derived from this enzyme with those of a more evolved protein containing additional point mutations, HG‐3.17, rendered important information that should be taken into account in the design of new enzymes. For this Kemp eliminase reaction, higher reactivity has been demonstrated to be related to a better electrostatic preorganisation of an environment that creates a more favourable electrostatic potential for the reaction to proceed. The limitations of HG‐3 can be related to a lack of flexibility, a not well‐fitted active site, and a lack of protein electrostatic preorganisation, which decrease the reorganisation around the oxyanion hole.
Insights into trans‐Ligand and Spin‐Orbit Effects on Electronic Structure and Ligand NMR Shifts in Transition‐Metal Complexes
Authors: Greif Anja H. , Hrobárik Peter , Kaupp Martin 
Published: March 2017

AbstractSurprisingly general effects of trans ligands L on the ligand NMR shifts in third‐row transition‐metal complexes have been found by quasi‐relativistic computations, encompassing 5d10, 5d8, and to some extent even 5d6 situations. Closer analysis, with emphasis on 1H shieldings in a series of linear HAuILq complexes, reveals a dominance of spin‐orbit (SO) effects, which can change sign from appreciably shielding for weak trans ligands to appreciably deshielding for ligands with strong trans influence. This may be traced back to increasing destabilization of a σ‐type MO at scalar relativistic level, which translates into very different σ‐/π‐mixing if SO coupling is included. For the strongest trans ligands, the σ‐MO may move above the highest occupied π‐type MOs, thereby dramatically reducing strongly shielding contributions from predominantly π‐type spinors. The effects of SO‐mixing are in turn related to angular momentum admixture from atomic spinors at the metal center. These SO‐induced trends hold for other nuclei and may also be used to qualitatively predict shifts in unknown complexes.
Stereoisomerism of bis(σ‐Zincane) Complexes: Evidence for an Intramolecular Pathway
Authors: Ekkert Olga , White Andrew J. P. , Crimmin Mark R. 
Published: March 2017

AbstractThe first bis(σ‐zincane) complexes, heterotri‐ metallic species [M(CO)4(η2‐HZnBDI)2], have been prepared (BDI=κ2‐{2,6‐(iPr)2C6H3NCMe}2CH). For M=Cr, a single stereoisomer is observed in solution and the solid‐state. For M=Mo and W, cis and trans isomers were found to reversibly interconvert at 297 K. Despite the huge steric demands of the ligand on zinc, the cis isomer was found to be the most thermodynamically stable in all cases. The activation parameters for the isomerisation when M=Mo are ΔH≠=20.8 kcal mol−1 and ΔS≠=−12.8 cal K−1 mol−1. In combination with DFT calculations, the negative activation entropy suggests an intramolecular rotation mechanism for isomerisation.
DESolution of CD and CB Macrocycles
Authors: McCune Jade A. , Kunz Susanna , Olesińska Magdalena , Scherman Oren A. 
Published: March 2017

AbstractSupramolecular chemistry utilizing the macrocyclic hosts cyclodextrins (CDs) and cucurbit[n]urils (CB[n]s) is traditionally performed in aqueous media; however, their solubility is typically poor, especially for the family of CB[n]s. Through derivatization of these macrocycles their solubility can be augmented to enable enhanced solubility in water and in some organic solvents. The increase in solubility of these derivatized macrocycles allows for their use in a wider range of chemical environments and giving rise to myriad potential applications. The dissolution of parent CDs (α‐, β‐ and γ‐) and CB[n]s (n=6–8) in deep eutectic solvents (DES) is reported, showing dramatic enhanced solubility of the larger species in both families, CB[7] and CB[8] as well as β‐ and γ‐CD, respectively. Furthermore, the host–guest properties are maintained in this new solvation medium.
Chirally sensitive collision induced dissociation of proton‐bound diastereomeric complexes of tryptophan and 2‐butanol
Authors: Rebrov Oleksii , Kulyk Kostiantyn , Ryding Mauritz , Thomas Richard D. , Uggerud Einar , Larsson Mats 
Published: March 2017

AbstractIn this work we report the stereo‐dependent collision‐induced dissociation (CID) of proton‐bound complexes of tryptophan and 2‐butanol. The dissociation efficiency was measured as a function of collision energy in single collision mode. The homochiral complex was found to be less stable against CID than a heterochiral one. Additional gas dependence measurements were performed with diastereomeric complexes that confirm the findings.
Iridium‐Catalyzed Reductive Amination of Levulinic Acid to Pyrrolidinones under H2 in Water
Authors: Xu Zhanwei , Yan Peifang , Jiang Hong , Liu Kairui , Zhang Z. Conrad 
Published: March 2017

AbstractThe synthesis of pyrrolidinones from reductive amination of levulinic acid (LA) with primary amines is reported. Pyrrolidinones have various applications such as surfactants, pharmaceutical intermediates, dispersants, and solvents. The half‐sandwich Cp*Ir complex (Cp* is 1,2,3,4,5‐pentamethylcyclopenta‐1,3‐diene) coordinated by bipyridine ligand bearing both dimethylamino and ortho‐hydroxyl groups showed high catalytic activity for the reductive amination of LA. A range of primary amines, such as aromatic and benzyl amines, were readily converted to corresponding pyrrolidinones in good yields.
Ventricular arrhythmias in patients with newly diagnosed nonischemic cardiomyopathy: Insights from the PROLONG study
Authors: Duncker David , König Thorben , Hohmann Stephan , Bauersachs Johann , Veltmann Christian 
Published: March 2017

BackgroundPatients with nonischemic cardiomyopathy (NICM) reportedly have low incidence of appropriate shocks from wearable cardioverter‐defibrillators (WCDs). A recent study questions the benefit from primary preventive implantation of implantable cardioverter‐defibrillators in NICM. We therefore analyzed a subgroup of patients with NICM from the PROLONG study.HypothesisPatients with newly diagnosed NICM show a risk for ventricular tachyarrhythmia.MethodsThe PROLONG study included 167 patients with newly diagnosed heart failure and left ventricular ejection fraction (LVEF) ≤35% with a WCD. Patients with NICM were identified and included in this analysis.Results117 patients presented with NICM. Sixty‐five (55%) were male; mean age was 51 ± 15 years. Mean LVEF at diagnosis was 23% ± 7%. Mean follow‐up was 11 ± 10 months. Mean WCD wear time was 101 ± 82 days; mean wear time per day was 21.4 ± 4.5 hours. Overall, 12 ventricular arrhythmias occurred in 10 (9%) patients (6 DCM, 4 PPCM). Nine appropriate WCD shocks for hemodynamically unstable ventricular tachycardia/fibrillation in 8 (7%) patients were observed. Two patients presented sustained hemodynamically stable ventricular tachycardia for >30 minutes detected by the WCD, but withheld WCD therapy.ConclusionsPatients with newly diagnosed NICM and LVEF ≤35% show an elevated risk of ventricular tachycardia/fibrillation during initiation and optimization of heart failure therapy. To prevent sudden cardiac death, WCD should be considered in patients with newly diagnosed NICM with severely reduced LVEF.
Elongated and Shortened Peptidomimetic Inhibitors of the Proprotein Convertase Furin
Authors: Hardes Kornelia , Ivanova Teodora , Thaa Bastian , McInerney Gerald M. , Klokk Tove Irene , Sandvig Kirsten , Künzel Sebastian , Lindberg Iris , Steinmetzer Torsten 
Published: March 2017

AbstractNovel elongated and shortened derivatives of the peptidomimetic furin inhibitor phenylacetyl‐Arg‐Val‐Arg‐4‐amidinobenzylamide were synthesized. The most potent compounds, such as Nα(carbamidoyl)Arg‐Arg‐Val‐Arg‐4‐amidinobenzylamide (Ki=6.2 pm), contain additional basic residues at the N terminus and inhibit furin in the low‐picomolar range. Furthermore, to decrease the molecular weight of this inhibitor type, compounds that lack the P5 moiety were prepared. The best inhibitors of this series, 5‐(guanidino)valeroyl‐Val‐Arg‐4‐amidinobenzylamide and its P3 tert‐leucine analogue displayed Ki values of 2.50 and 1.26 nm, respectively. Selected inhibitors, together with our previously described 4‐amidinobenzylamide derivatives as references, were tested in cell culture for their activity against furin‐dependent infectious pathogens. The propagation of the alphaviruses Semliki Forest virus and chikungunya virus was strongly inhibited in the presence of selected derivatives. Moreover, a significant protective effect of the inhibitors against diphtheria toxin was observed. These results confirm that the inhibition of furin should be a promising approach for the short‐term treatment of acute infectious diseases.
Are there patients with T1 to T2, lymph node‐negative breast cancer who are “high‐risk” for locoregional disease recurrence?
Authors: Mamtani Anita , Patil Sujata , Stempel Michelle M. , Morrow Monica 
Published: March 2017

BACKGROUNDIndications for postmastectomy radiotherapy (PMRT) in patients with T1 to T2, lymph node‐negative (N0) breast cancer with “high‐risk” features are controversial. The European Organization for Research and Treatment of Cancer (EORTC) 22922 and National Cancer Institute of Canada Clinical Trials Group MA20 trials reporting improved 10‐year disease‐free survival with lymph node irradiation included patients with high‐risk N0 disease, but, to the authors’ knowledge, benefits in patients receiving modern systemic therapy are uncertain.METHODSThe authors retrospectively identified patients with T1 to T2N0 disease who were treated with mastectomy from January 2006 through December 2011. High‐risk features included age <40 years, multifocality/multicentricity, lymphovascular invasion, medial/central tumor location, and high nuclear grade.RESULTSAmong 672 eligible patients, only 15 received PMRT and were excluded. Of the remaining 657 patients, 187 (28%) had 1 high‐risk feature and 449 patients (68%) had ≥ 2 high‐risk features. A total of 36 patients with unknown tumor grade were excluded from risk analysis. Approximately 98% of patients underwent sentinel lymph node biopsy alone and 86% received adjuvant systemic therapy. At a median of 5.6 years of follow‐up, the locoregional disease recurrence (LRR) rate was 4.7% (31 patients). Increasing tumor size was found to be associated with LRR (hazard ratio, 1.70; P = .006), whereas other high‐risk features were not (all P > .05). Receipt of systemic therapy decreased the LRR rate (hazard ratio, 0.40; P = .03). Although crude LRR rates increased from 3.8% to 9.4% with 1 versus ≥ 4 high‐risk features, the number of risk factors was not found to be significantly associated with LRR (P = .54).CONCLUSIONSIn the current study, a low crude LRR rate (4.7%) was observed in a large unselected cohort of patients with T1 to T2N0 breast cancer with high‐risk features who were treated with mastectomy and systemic therapy without PMRT. Although increasing tumor size and the omission of systemic therapy were found to be predictive, other features did not confer a higher LRR risk either independently or together, and do not by themselves mandate the use of PMRT in this patient population. Cancer 2017;123:2626‐33. © 2017 American Cancer Society.
A phase 2 trial of dasatinib in patients with locally advanced or stage IV mucosal, acral, or vulvovaginal melanoma: A trial of the ECOG‐ACRIN Cancer Research Group (E2607)
Authors: Kalinsky Kevin , Lee Sandra , Rubin Krista M. , Lawrence Donald P. , Iafrarte Anthony J. , Borger Darell R. , Margolin Kim A. , Leitao Mario M. , Tarhini Ahmad A. , Koon Henry B. , Pecora Andrew L. , Jaslowski Anthony J. , Cohen Gary I. , Kuzel Timothy M. , Lao Christopher D. , Kirkwood John M. 
Published: March 2017

BACKGROUNDKIT‐directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT‐mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun‐damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11L576P. The ECOG‐ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes.METHODSPatients received 70 mg of oral dasatinib twice daily. The primary objective for this 2‐stage phase 2 trial was response rate. Stage I was open to KIT+ and wild‐type KIT (KIT–) mucosal, acral, and CSD melanoma (n = 57). Stage II accrued only KIT+ tumors (n = 30). To enrich the trial for KIT+ tumors, vulvovaginal melanoma was added, and CSD melanoma was removed from eligibility. Secondary objectives included progression‐free survival (PFS), overall survival (OS), and safety.RESULTSFrom May 2009 to December 2010, the first stage enrolled 57 patients. Among the evaluable patients, 3 of 51 (5.9%) achieved a partial response: all were KIT–. Stage II closed early because of slow accrual (November 2011 to December 2015). In stage II, 4 of 22 evaluable patients (18.2%) had a partial response; the median duration was 4.2 months. The median PFS was 2.1 months (n = 73; 95% confidence interval [CI], 1.5‐2.9 months). The median OS was 7.5 months (95% CI, 6.0‐11.9 months). In exploratory analyses, no differences were seen in PFS or OS with the KIT status or subtype. Dasatinib was discontinued because of adverse events in 9 of 75 patients (12%).CONCLUSIONSThe dasatinib response rate among KIT+ melanoma patients was low. In view of its clinical activity, it is recommended that imatinib remain the KIT tyrosine kinase inhibitor of choice for unresectable KIT+ melanoma. Cancer 2017;123:2688‐97. © 2017 American Cancer Society.