bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining Copper‐Catalyzed Hydroboration with Palladium‐Catalyzed Suzuki Coupling for the One‐pot Synthesis of Arylallylamines under Micellar Conditions
Authors: Horn Pedro A. , Braun Roger K. , Isoppo Victória G. , Costa Jessie S. da , Lüdtke Diogo S. , Moro Angélica V. 
Published: April 2017

AbstractHerein we report the one‐pot dual‐metal catalytic synthesis of arylallylamines, by combination of a Cu‐catalyzed hydroboration with a Pd‐catalyzed Suzuki arylation, using a broad range of aryl halides. Importantly, the reaction sequence was entirely performed in water, in the presence of small amounts of SPGS‐550M, without the need of solvent switch or addition of organic co‐solvents, rendering it operationally simple and environmentally benign. The usefulness of this methodology was highlighted in a short synthesis of the pharmaceutically important compound naftifine.magnified image
Photoinduced Copper(I)‐Catalyzed Cyanation of Aromatic Halides at Room Temperature
Authors: Kim Kicheol , Hong Soon Hyeok 
Published: April 2017

AbstractThe first photoinduced copper(I)‐catalyzed cyanation of aromatic halides at room temperature has been developed. The sp2 cyanation reaction exhibits outstanding tolerance to functional groups including primary amines and carboxylic acids, and chemoselectivity to SN2‐reactive alkyl chlorides. Mechanistic investigations indicate that the reaction occurs via a single‐electron transfer (SET) between the aryl halide and an excited copper(I) cyanide catalytic intermediate.magnified image
An Ion‐Responsive Pincer‐Crown Ether Catalyst System for Rapid and Switchable Olefin Isomerization
Authors: Kita Matthew R. , Miller Alexander J. M. 
Published: April 2017

AbstractRapid, selective, and highly controllable iridium‐catalyzed allylbenzene isomerization is described, enabled by tunable hemilability based on alkali metal cation binding with a macrocyclic “pincer‐crown ether” ligand. An inactive chloride‐ligated complex can be activated by halide abstraction with sodium salts, with the resulting catalyst [κ5‐(15c5NCOPiPr)Ir(H)]+ exhibiting modest activity. Addition of Li+ provides a further boost in activity, with up to 1000‐fold rate enhancement. Ethers and chloride salts dampen or turn off reactivity, leading to three distinct catalyst states with activity spanning several orders of magnitude. Mechanistic studies suggest that the large rate enhancement and high degree of tunability stem from control over substrate binding.
A Vicinal Electrophilic Diborylation Reaction Furnishes Doubly Boron‐Doped Polycyclic Aromatic Hydrocarbons
Authors: John Alexandra , Bolte Michael , Lerner Hans‐Wolfram , Wagner Matthias 
Published: April 2017

AbstractTen examples of unsymmetrically benzannulated, boron‐doped polycyclic aromatic hydrocarbons (B‐PAHs) were prepared by a one‐pot protocol using 4,5‐dichloro‐1,2‐bis(trimethylsilyl)benzene (1), BBr3, and selected PAHs—among them anthracene, benzo[a]pyrene, biphenylene, and fluoranthene. After mesitylation at the boron centers, the resulting air‐ and water‐stable products were investigated by 1H/11B{1H}/13C{1H} NMR spectroscopy, X‐ray crystallography, cyclic voltammetry, and UV/Vis absorption/emission spectroscopy. The experiments were augmented by DFT calculations. Most of the B‐PAHs are brightly luminescent (ΦPL up to 90 %) and undergo reversible reduction at moderate half‐wave potentials. The two chloro substituents of 1 are not only mandatory for accomplishing efficient diborylation, but can subsequently be used for Stille‐type coupling reactions to introduce 2‐thienyl moieties. Alternatively, Cl/H exchange is achievable with HSiEt3 in a quantitative, Pd‐catalyzed transformation.
The Reactivity of Benzyl Lithium Species is Regulated by Intermediate Structures
Authors: Kroesen Ulrike , Knauer Lena , Strohmann Carsten 
Published: April 2017

AbstractThe reaction of benzyl lithiums is an important aspect in organic and organometallic synthesis. Reported herein are detailed insights into the reactivity of benzyl lithiums as regulated by intermediate structures. By discussing the carbometalation of allylamines and the reaction of the formed benzyl‐lithium compounds with electrophiles, the influence of the metal as well as the solvent on the electronic structure of the intermediate is described. This molecular structure strongly influences the reactivity of these intermediates. By choosing the appropriate reaction conditions, the regioselectivity of reactions with electrophiles can be regulated. With trimethylchlorosilane in n‐pentane a selective reaction at the para‐position takes place. In contrast, selective reaction at the benzylic position, with trimethylchlorostannane in tetrahydrofuran (THF) as a solvent, is accomplished.
A Highly Active Manganese Catalyst for Enantioselective Ketone and Ester Hydrogenation
Authors: Widegren Magnus B. , Harkness Gavin J. , Slawin Alexandra M. Z. , Cordes David B. , Clarke Matthew L. 
Published: April 2017

AbstractA new hydrogenation catalyst based on a manganese complex of a chiral P,N,N ligand has been found to be especially active for the hydrogenation of esters down to 0.1 mol % catalyst loading, and gives up to 97 % ee in the hydrogenation of pro‐chiral deactivated ketones at 30–50 °C.
Influence of seasonality on cetacean diversity, abundance, distribution and habitat use in the western Mediterranean Sea: Implications for conservation
Authors: Arcangeli Antonella , Campana Ilaria , Bologna Marco A. 
Published: April 2017

Abstract

Cetaceans are key biological indicators of the status of marine waters and are protected under an extensive legislative framework. Research about these highly dynamic species is challenging, so seasonal cycles and patterns of distribution, especially in high sea areas, are still poorly understood.
This study contributes to improving knowledge about cetacean occurrence in largely unexplored areas of medium‐latitudes in the western Mediterranean Sea. Systematic surveys were conducted along a trans‐regional transect over 3 years (October 2012 to September 2015) allowing consistent data collection over almost 60 000 km of effort through all seasons.
Seasonal cetacean diversity was investigated using a 25 km2 grid cell as a statistical unit to explore patterns of abundance, distribution, and habitat use in three marine sectors (Sardinian–Balearic, Bonifacio Strait, Tyrrhenian). All cetacean species regularly present in the Mediterranean basin were detected, with highest occurrence in fin whale and striped dolphin, followed by bottlenose dolphin and sperm whale.
The Sardinian–Balearic sector generally showed higher species richness and diversity than the Tyrrhenian, where seasonal variations were more pronounced. The study suggested seasonal movements, especially for fin whale and striped dolphin, in the Sardinian–Balearic sector with peaks of occurrence during spring/summer and lower numbers during winter/autumn, and also delivered interesting insights to rarer pelagic species.
The study identified areas/seasons in which the combined effect of high species diversity, abundance, significance of hot spots and presence of juveniles require increasing conservation effort. Results underline the important contribution of continuous monitoring in high sea areas to the implementation of adaptive protection measures.
The Therapeutic Efficacy of Botulinum Toxin in Treating Scleroderma‐Associated Raynaud's Phenomenon: A Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial
Authors: Bello Ricardo J. , Cooney Carisa M. , Melamed Eitan , Follmar Keith , Yenokyan Gayane , Leatherman Gwendolyn , Shah Ami A. , Wigley Fredrick M. , Hummers Laura K. , Lifchez Scott D. 
Published: April 2017

ObjectiveTo assess the therapeutic efficacy of local injections of botulinum toxin type A (Btx‐A) in improving blood flow to the hands of patients with Raynaud's phenomenon (RP) secondary to scleroderma.MethodsIn this randomized, double‐blind, placebo‐controlled clinical trial, patients with scleroderma‐associated RP received Btx‐A (50 units in 2.5 ml sterile saline) in one randomly selected hand and sterile saline (2.5 ml) in the opposite hand. Follow‐up at 1 and 4 months postinjection included laser Doppler imaging of hands, patient‐reported outcomes, and physical examination. We compared outcomes using paired t‐tests and population‐average generalized models with generalized estimating equations.ResultsOf 40 patients enrolled, 25 had limited scleroderma and 15 had diffuse scleroderma. From baseline to 1‐month follow‐up, there was a greater reduction in average blood flow in Btx‐A–treated hands compared to placebo‐treated hands. The model estimated that this difference was statistically significant (average difference −30.08 flux units [95% confidence interval −56.19, −3.98], P for interaction = 0.024). This difference was mainly influenced by patients with longstanding RP and diffuse scleroderma. Change in blood flow at 4‐month follow‐up was not significantly different between groups. Clinical measures (QuickDASH, McCabe Cold Sensitivity Score, pain on a visual analog scale, and Raynaud's Condition Score) improved slightly for Btx‐A–treated hands.ConclusionOur laboratory‐based laser Doppler imaging flow data do not support using Btx‐A to treat RP in all scleroderma patients. The secondary clinical outcomes suggest some positive effect, but its clinical meaningfulness is questionable. The role of Btx‐A in treating RP should be further studied with more homogeneous patient populations and in unique clinical situations such as acute digital ischemia.
Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?
Authors: Levina Aviva , Lay Peter A. 
Published: April 2017

AbstractDiverse biological activities of vanadium(V) drugs mainly arise from their abilities to inhibit phosphatase enzymes and to alter cell signaling. Initial interest focused on anti‐diabetic activities but has shifted to anti‐cancer and anti‐parasitic drugs. V‐based anti‐diabetics are pro‐drugs that release active components (e.g., H2VO4−) in biological media. By contrast, V anti‐cancer drugs are generally assumed to enter cells intact; however, speciation studies indicate that nearly all drugs are likely to react in cell culture media during in vitro assays and the same would apply in vivo. The biological activities are due to VV and/or VIV reaction products with cell culture media, or the release of ligands (e.g., aromatic diimines, 8‐hydroxyquinolines or thiosemicarbazones) that bind to essential metal ions in the media. Careful consideration of the stability and speciation of V complexes in cell culture media and in biological fluids is essential to design targeted V‐based anti‐cancer therapies.
Seeing into the Future: Future Time Orientation as a Moderator of Temporal Distance Effects on Educators' Decisions
Authors: Kogut Tehila , Eyal Tal , Sharon Idit 
Published: April 2017

AbstractResearch suggests that the temporal distance from decision outcomes leads to divergent decisions for the near and the distal future. As such, high‐level idealistic concerns and values dominate decisions for the distant future, whereas low‐level pragmatic concerns play a greater role in decisions for the near future. We examined how individual differences in future time orientation are related to decisions vis‐à‐vis the near versus the distal future. The results of three studies, with participants with varying levels of expertise—students (Studies 2 and 3), teachers (Study 1), and school principals (Study 2)—show that principals tend to be overall more idealistic in their choices. Yet discrepancies between decisions for the near versus the distal future exist among all three levels of expertise. However, this dominance of idealistic over pragmatic concerns for more distant future decisions effect was smaller the higher the future time orientation was (whether measured or manipulated). Implications for educational and managerial decision making and training are discussed. Copyright © 2017 John Wiley & Sons, Ltd.
Congenital Lung Agenesis: Incidence and Outcome in the North of England
Authors: Thomas Matthew , Robertson Nic , Miller Nicola , Rankin Judith , McKean Michael , Brodlie Malcom 
Published: April 2017

BackgroundUnilateral lung agenesis is an uncommon congenital abnormality, with a lack of reported accurate incidence estimates. Prognosis is also uncertain, with older literature reporting poor outcomes.MethodsThe North of England register of congenital anomalies (Northern Congenital Abnormality Survey) records cases of congenital anomalies to mothers' resident in the region. We used the register to identify all patients with congenital lung agenesis born between 2004 and 2013 to calculate an accurate incidence estimate and report clinical outcomes with contemporary management.ResultsFour patients with congenital lung agenesis were born during the study period, giving an estimated incidence in the North of England of 1.22 per 100,000 live births (95% confidence interval, 0.33–3.11). Two patients had associated congenital heart disease requiring corrective surgery, and one had musculoskeletal anomalies. All four patients are alive and well without a regular oxygen requirement.ConclusionContrary to previous reports, the medium term outcomes in our patients have been good, even when lung agenesis is associated with other congenital anomalies. Long‐term prognosis with modern management remains unknown, and the potential for the development of pulmonary hypertension remains a concern. Birth Defects Research 109:857–859, 2017. © 2017 Wiley Periodicals, Inc.
Alcohol‐tolerant mutants of cyanobacterium Synechococcus elongatus PCC 7942 obtained by single‐cell mutant screening system
Authors: Arai Sayuri , Hayashihara Kayoko , Kanamoto Yuki , Shimizu Kazunori , Hirokawa Yasutaka , Hanai Taizo , Murakami Akio , Honda Hiroyuki 
Published: April 2017

ABSTRACTEnhancement of alcohol tolerance in microorganisms is an important strategy for improving bioalcohol productivity. Although cyanobacteria can be used as a promising biocatalyst to produce various alcohols directly from CO2, low productivity, and low tolerance against alcohols are the main issues to be resolved. Nevertheless, to date, a mutant with increasing alcohol tolerance has rarely been reported. In this study, we attempted to select isopropanol (IPA)‐tolerant mutants of Synechococcus elongatus PCC 7942 using UV‐C‐induced random mutagenesis, followed by enrichment of the tolerant candidates in medium containing 10 g/L IPA and screening of the cells with a high growth rate in the single cell culture system in liquid medium containing 10 g/L IPA. We successfully acquired the most tolerant strain, SY1043, which maintains the ability to grow in medium containing 30 g/L IPA. The photosynthetic oxygen‐evolving activities of SY1043 were almost same in cells after 72 h incubation under light with or without 10 g/L IPA, while the activity of the wild‐type was remarkably decreased after the incubation with IPA. SY1043 also showed higher tolerance to ethanol, 1‐butanol, isobutanol, and 1‐pentanol than the wild type. These results suggest that SY1043 would be a promising candidate to improve alcohol production using cyanobacteria. Biotechnol. Bioeng. 2017;114: 1771–1778. © 2017 Wiley Periodicals, Inc.
Autodisplay of glucose‐6‐phosphate dehydrogenase for redox cofactor regeneration at the cell surface
Authors: Schüürmann Jan , Quehl Paul , Lindhorst Fabian , Lang Kristina , Jose Joachim 
Published: April 2017

ABSTRACTInherent cofactor regeneration is a pivotal feature of whole cell biocatalysis. For specific biotechnological applications, surface display of enzymes is emerging as a tool to circumvent mass transfer limitations or enzyme stability problems. Even complex reactions can be accomplished applying displayed enzymes. Yet, industrial utilization of the technique is still impeded by lacking cofactor regeneration at the cell surface. Here, we report on the surface display of a glucose‐6‐phoshate dehydrogenase (G6PDH) via Autodisplay to address this limitation and regenerate NADPH directly at the cell surface. The obtained whole cell biocatalyst demonstrated similar kinetic parameters compared to the purified enzyme, more precisely KM values of 0.2 mM for NADP+ and calculated total turnover numbers of 107. However, the KM for the substrate G6P increased by a factor of 7 to yield 1.5 mM. The whole cell biocatalyst was cheaper to produce, easy to separate from the reaction mixture and reusable in consecutive reaction cycles. Furthermore, lyophilization allowed storage at room temperature. The whole cell biocatalyst displaying G6PDH was applicable for NADPH regeneration in combination with soluble as well as surface displayed enzymes and model reactions in combination with bacterial CYP102A1 and human CYP1A2 were realized. Biotechnol. Bioeng. 2017;114: 1658–1669. © 2017 Wiley Periodicals, Inc.
A plug‐and‐play pathway refactoring workflow for natural product research in Escherichia coli and Saccharomyces cerevisiae
Authors: Ren Hengqian , Hu Pingfan , Zhao Huimin 
Published: April 2017

ABSTRACTPathway refactoring serves as an invaluable synthetic biology tool for natural product discovery, characterization, and engineering. However, the complicated and laborious molecular biology techniques largely hinder its application in natural product research, especially in a high‐throughput manner. Here we report a plug‐and‐play pathway refactoring workflow for high‐throughput, flexible pathway construction, and expression in both Escherichia coli and Saccharomyces cerevisiae. Biosynthetic genes were firstly cloned into pre‐assembled helper plasmids with promoters and terminators, resulting in a series of expression cassettes. These expression cassettes were further assembled using Golden Gate reaction to generate fully refactored pathways. The inclusion of spacer plasmids in this system would not only increase the flexibility for refactoring pathways with different number of genes, but also facilitate gene deletion and replacement. As proof of concept, a total of 96 pathways for combinatorial carotenoid biosynthesis were built successfully. This workflow should be generally applicable to different classes of natural products produced by various organisms. Biotechnol. Bioeng. 2017;114: 1847–1854. © 2017 Wiley Periodicals, Inc.
Competing risks analysis of microsatellite instability as a prognostic factor in colorectal cancer
Authors: Toh J , Chapuis P H , Bokey L , Chan C , Spring K J , Dent O F 
Published: April 2017

Abstract

Background
Despite an extensive literature suggesting that high microsatellite instability (MSI-H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk.

Methods
A hospital database of patients following colorectal cancer resection was interrogated for clinical, operative, pathology, adjuvant therapy and follow-up information. MSI-H status was determined by immunohistochemistry for mismatch repair protein deficiency. The cumulative incidence of recurrence and colorectal cancer-specific death was evaluated by competing risks methods.

Results
Among 1009 patients who had a resection between August 2002 and December 2008, and were followed to at least December 2013, there were 114 (11·3 per cent) with MSI-H (72·8 per cent aged at least 70 years; 63·2 per cent women). After potentially curative resection, with adjustment for non-colorectal cancer death as a competing risk and adjustment for 22 clinical, operative and pathological variables, there was no association between MSI-H and recurrence (hazard ratio (HR) 0·81, 95 per cent c.i. 0·42 to 1·57) or colorectal cancer-specific death (HR 0·73, 0·39 to 1·35) in this patient population. For palliative resections, there was no association between MSI-H and colorectal cancer-specific death (HR 0·65, 0·21 to 2·04). MSI-H was associated with non-colorectal cancer death after both curative (HR 1·55, 1·04 to 2·30) and palliative (HR 3·80, 1·32 to 11·00) resections.

Conclusion
Microsatellite instability status was not an independent prognostic variable in these patients.
Simultaneous determination of difenoconazole, trifloxystrobin and its metabolite trifloxystrobin acid residues in watermelon under field conditions by GC–MS/MS
Authors: Kang Di , Zhang Haizhen , Chen Yuling , Wang Fei , Shi Lihong , Hu Deyu , Zhang Kankan 
Published: April 2017

AbstractAn optimized quick, easy, cheap, effective, rugged and safe method for the simultaneous determination of difenoconazole, trifloxystrobin and its metabolite trifloxystrobin acid residues in watermelon and soil was developed and validated by gas chromatography with tandem mass spectrometry. The samples were extracted with acetonitrile (1% formic acid) and cleaned up by dispersive solid‐phase extraction with octadecylsilane sorbent. The limit of quantification of the method was 0.01 mg/kg, and the limit of detection was 0.003 mg/kg for all three analytes. The recoveries of the fungicides in watermelon, pulp and soil were 72.32–99.20% for difenoconazole, 74.68–87.72% for trifloxystrobin and 78.59–92.66% for trifloxystrobin acid with relative standard deviations of 1.34–14.04%. The dissipation dynamics of difenoconazole and trifloxystrobin in watermelon and soil followed the first‐order kinetics with half‐lives of 3.2–8.8 days in both locations. The final residue levels of difenoconazole and trifloxystrobin were below 0.1 mg/kg (maximum residue level [MRL] set by China) and 0.2 mg/kg (MRL set by European Union), respectively, in pulp samples collected 14 days after the last application. These results could help Chinese authorities to establish MRL of trifloxystrobin in watermelon and provide guidance for the safe and proper application of both fungicides on watermelon.
Simultaneous quantification and semi‐quantification of amentoflavone and its metabolites in human intestinal bacteria by liquid chromatography Orbitrap high‐resolution mass spectrometry
Authors: Qian Yiyun , Jiang Shu , Zhu Zhenhua , Wang Qi , Su Shulan , Tao Jinhua , Duan Jin‐ao 
Published: April 2017

AbstractA quick, easy, effective method followed by ultra‐high‐pressure liquid chromatography coupled with linear ion trap–Orbitrap tandem mass spectrometry (UHPLC‐LTQ‐Orbitrap MS) was developed for the simultaneous identification and quantification of the metabolites produced by amentoflavone (AMF) in human intestinal bacteria from human feces. The method validated for quantification of AMF concerning precision, accuracy, recovery, matrix effect, stability and limits showed acceptable results. Compared with blank human intestinal bacteria chromatography, three metabolites were identified based on high‐accuracy protonated precursors and multi‐stage mass spectrometry (MSn) using the proposed strategy. At the same time, a new method was developed for semi‐quantification of three metabolites. We describe the trend over 24 h of concentration–time curves for AMF and its metabolites. Moreover, the main metabolic pathway of AMF was clarified in human intestinal bacteria. The method was validated and successfully applied to the detection and quantification of AMF and its metabolites.