bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of a Doubly Boron‐Doped Perylene through NHC‐Borenium Hydroboration/C−H Borylation/Dehydrogenation
Authors: Farrell Jeffrey M. , Schmidt David , Grande Vincenzo , Würthner Frank
Published: July 2017

Reaction of an N‐heterocyclic carbene (NHC)–borenium ion with 9,10‐distyrylanthracene forms four B−C bonds through two selective, tandem hydroboration–electrophilic C−H borylations to yield an isolable, crystallographically characterizable polycyclic diborenium ion as its [NTf2]− salt (1). Dehydrogenation of 1 with TEMPO radical followed by acidic workup yields a 3,9‐diboraperylene as its corresponding borinic acid (2). This sequence can be performed in one pot to allow the facile, metal‐free conversion of an alkene into a small molecule containing a boron‐doped graphene substructure. Doubly boron‐doped perylene 2 exhibits visible range absorbance and fluorescence in chloroform solution (Φ=0.63) and undergoes two reversible one‐electron reductions at moderate potentials of −1.30 and −1.64 eV vs. ferrocenium/ferrocene in DMSO. Despite sterically accessible boron centers and facile electrochemical reductions, compound 2 is air‐, moisture‐, and silica gel‐stable.
Synthese von Diorganomagnesium‐ und Diorganozinkverbindungen durch In‐Situ‐Abfang‐Halogen‐Lithium‐Austausch an hochfunktionalisierten (Hetero)Arylhalogeniden im kontinuierlichen Durchfluss
Authors: Ketels Marthe , Ganiek Maximilian A. , Weidmann Niels , Knochel Paul
Published: July 2017

Der Halogen‐Lithium‐Austausch in Gegenwart von Metallsalzen (ZnCl2, MgCl2⋅LiCl) an einer Vielzahl empfindlicher Brom‐ und Iod‐(Hetero)Arene mit BuLi oder PhLi als Austauschreagenz im kontinuierlichen Durchfluss wird beschrieben. Die entstehenden Diarylmagnesium‐ und Diarylzinkspezies werden mit verschiedenen Elektrophilen abgefangen, und es werden polyfunktionalisierte (Hetero)Arene in hohen Ausbeuten erhalten. Diese Methode ermöglicht die Funktionalisierung von (Hetero)Arenen mit hochempfindlichen Isothiocyanat‐, Nitro‐, Azid‐ oder Estergruppen. Eine Skalierung ist ohne weitere Optimierungen möglich.
Exclusive Formation of Formic Acid from CO2 Electroreduction by a Tunable Pd‐Sn Alloy
Authors: Bai Xiaofang , Chen Wei , Zhao Chengcheng , Li Shenggang , Song Yanfang , Ge Ruipeng , Wei Wei , Sun Yuhan
Published: July 2017

Conversion of carbon dioxide (CO2) into fuels and chemicals by electroreduction has attracted significant interest, although it suffers from a large overpotential and low selectivity. A Pd‐Sn alloy electrocatalyst was developed for the exclusive conversion of CO2 into formic acid in an aqueous solution. This catalyst showed a nearly perfect faradaic efficiency toward formic acid formation at the very low overpotential of −0.26 V, where both CO formation and hydrogen evolution were completely suppressed. Density functional theory (DFT) calculations suggested that the formation of the key reaction intermediate HCOO* as well as the product formic acid was the most favorable over the Pd‐Sn alloy catalyst surface with an atomic composition of PdSnO2, consistent with experiments.
Controlled Supramolecular Self‐Assembly of Super‐charged β‐Lactoglobulin A–PEG Conjugates into Nanocapsules
Authors: Khan Amit Kumar , Gudlur Sushanth , de Hoog Hans‐Peter M. , Siti Winna , Liedberg Bo , Nallani Madhavan
Published: July 2017

The synthesis and characterization of a new protein–polymer conjugate composed of β lactoglobulin A (βLG A) and poly(ethylene glycol) PEG is described. βLG A was selectively modified to self‐assemble by super‐charging via amination or succinylation followed by conjugation with PEG. An equimolar mixture of the oppositely charged protein–polymer conjugates self‐assemble into spherical capsules of 80–100 nm in diameter. The self‐assembly proceeds by taking simultaneous advantage of the amphiphilicity and polyelectrolyte nature of the protein–polymer conjugate. These protein–polymer capsules or proteinosomes are reminiscent of protein capsids, and are capable of encapsulating solutes in their interior. We envisage this approach to be applicable to other globular proteins.
Directing the Activation of Donor–Acceptor Cyclopropanes Towards Stereoselective 1,3‐Dipolar Cycloaddition Reactions by Brønsted Base Catalysis
Authors: Blom Jakob , Vidal‐Albalat Andreu , Jørgensen Julie , Barløse Casper L. , Jessen Kamilla S. , Iversen Marc V. , Jørgensen Karl Anker
Published: July 2017

The first stereoselective organocatalyzed [3+2] cycloaddition reaction of donor‐acceptor cyclopropanes is presented. It is demonstrated that by applying an optically active bifunctional Brønsted base catalyst, racemic di‐cyano cyclopropylketones can be activated to undergo a stereoselective 1,3‐dipolar reaction with mono‐ and polysubstituted nitroolefins. The reaction affords functionalized cyclopentanes with three consecutive stereocenters in high yield and stereoselectivity. Based on the stereochemical outcome, a mechanism in which the organocatalyst activates both the donor‐acceptor cyclopropane and nitroolefin is proposed. Finally, chemoselective transformations of the cycloaddition products are demonstrated.
Synthesis of Polyfunctional Diorganomagnesium and Diorganozinc Reagents through In Situ Trapping Halogen–Lithium Exchange of Highly Functionalized (Hetero)aryl Halides in Continuous Flow
Authors: Ketels Marthe , Ganiek Maximilian A. , Weidmann Niels , Knochel Paul
Published: July 2017

We report a halogen–lithium exchange performed in the presence of various metal salts (ZnCl2, MgCl2⋅LiCl) on a broad range of sensitive bromo‐ or iodo(hetero)arenes using BuLi or PhLi as the exchange reagent and a commercially available continuous‐flow setup. The resulting diarylmagnesium or diarylzinc species were trapped with various electrophiles, resulting in the formation of polyfunctional (hetero)arenes in high yields. This method enables the functionalization of (hetero)arenes containing highly sensitive groups such as an isothiocyanate, nitro, azide, or ester. A straightforward scale‐up was possible without further optimization.
Fluorescence and Sensing Applications of Graphene Oxide and Graphene Quantum Dots: A Review
Authors: Zheng Peng , Wu Nianqiang
Published: July 2017

Graphene oxide and graphene quantum dots are attractive fluorophores that are inexpensive, nontoxic, photostable, water‐soluble, biocompatible, and environmentally friendly. They find extensive applications in fluorescent biosensors and chemosensors, in which they serve as either fluorophores or quenchers. As fluorophores, they display tunable photoluminescence emission and the “giant red‐edge effect”. As quenchers, they exhibit a remarkable quenching efficiency through either electron transfer or Förster resonance energy transfer (FRET) process. In this review, the origin of fluorescence and the mechanism of excitation wavelength‐dependent fluorescence of graphene oxide and graphene quantum dots are discussed. Sensor design strategies based on graphene oxide and graphene quantum dots are presented. The applications of these sensors in health care, the environment, agriculture, and food safety are highlighted.
Prediction and attribution of quiescent tropical cyclone activity in the early summer of 2016: case study of lingering effects by preceding strong El Niño events
Authors: Takaya Yuhei , Kubo Yutaro , Maeda Shuhei , Hirahara Shoji
Published: July 2017

We investigated mechanisms contributing to the quiescent tropical cyclone (TC) activity in the western North Pacific (WNP) during the early summer (May–July) of 2016 by conducting and analysing seasonal predictions and sensitivity experiments with an atmosphere–ocean coupled model. In the seasonal prediction experiment, the model successfully predicted the inactive TC condition. Sensitivity experiment simulations, in which the warmer‐than‐normal sea surface temperature (SST) in the Indian Ocean (IO) was restored to the climatology, represented a weakened lower‐tropospheric anticyclonic anomaly and near‐normal TC activity over the WNP. These results suggest that the quiescent TC activity is attributable to the warm IO SST anomalies induced by the preceding 2015/2016 El Niño. Verification and analysis of reforecasts indicated that the TC count in early summer is highly predictable due to IO warming, a lingering effect of preceding El Niño events.
Differential intensity‐dependent effects of pulsed electromagnetic fields on RANKL‐induced osteoclast formation, apoptosis, and bone resorbing ability in RAW264.7 cells
Authors: Wang Pan , Liu Juan , Yang Yuefan , Zhai Mingming , Shao Xi , Yan Zedong , Zhang Xuhui , Wu Yan , Cao Lu , Sui Bingdong , Luo Erping , Jing Da
Published: July 2017

Pulsed electromagnetic fields (PEMF) have been proven to be effective for promoting bone mass and regulating bone turnover both experimentally and clinically. However, the exact mechanisms for the regulation of PEMF on osteoclastogenesis as well as optical exposure parameters of PEMF on inhibiting osteoclastic activities and functions remain unclear, representing significant limitations for extensive scientific application of PEMF in clinics. In this study, RAW264.7 cells incubated with RANKL were exposed to 15 Hz PEMF (2 h/day) at various intensities (0.5, 1, 2, and 3 mT) for 7 days. We demonstrate that bone resorbing capacity was significantly decreased by 0.5 mT PEMF mainly by inhibiting osteoclast formation and maturation, but enhanced at 3 mT by promoting osteoclast apoptosis. Moreover, gene expression of RANK, NFATc1, TRAP, CTSK, BAX, and BAX/BCL‐2 was significantly decreased by 0.5 mT PEMF, but increased by 3 mT. Our findings reveal a significant intensity window for low‐intensity PEMF in regulating bone resorption with diverse nature for modulating osteoclastogenesis and apoptosis. This study not only enriches our basic knowledge for the regulation of PEMF in osteoclastogenesis, but also may lead to more efficient and scientific clinical application of PEMF in regulating bone turnover and inhibiting osteopenia/osteoporosis. Bioelectromagnetics. 38:602–612, 2017. © 2017 Wiley Periodicals, Inc.
Engineering Studies on Moisture Diffusivity of Solid Food Products during Processing – A Review
Authors: Subramanyam Rajasekar , Narayanan Meyyappan , Rao Dubasi Govardhana
Published: July 2017

Drying is a simultaneous heat and mass transfer operation and is extensively applied in food processing to extend the shelf life of food products and agri‐produce by reducing the moisture content which in turn reduces the water activity. Moisture content is a major culprit in spoiling the foods by encouraging microbial/mold growth. Hence, the reducing moisture content economically mitigates the spoilage of foods. A number of commercial dryers is available industrially for carrying out drying operations depending on the nature of food material. However, from economic points of view, tray dryers are ubiquitous. Hence, this review focuses on explaining in‐detail the design of tray dryers with an aid of CFD, mathematical tools, and statistical analysis used in diffusivity of food products. The drying process is influenced by various operating parameters such as drying chamber configuration, air velocity, and air temperature, etc. which need to be optimized to properly design a dryer for a certain duty of operation. This paper reviews the studies in this area by applying mathematical tools, statistical analysis, and CFD.
Keep your eye on…
Authors: Knopf Alison
Published: July 2017

Concerns about use of antidepressants in pregnancy and ID in children

The high rate of cigarette use by youth — and the desire to quit
Nickel/USY Catalyst Derived from a Layered Double Hydroxide/Zeolite Hybrid Structure with a High Hydrogenation Efficiency
Authors: Wang Bo , Wang Darui , Guan Yejun , Xu Hao , Zhang Lin , Wu Peng
Published: July 2017

It is important and challenging in heterogeneous catalysis to prepare catalysts with highly dispersed metal nanoparticles that have a high activity. Herein, a new Ni/USY catalyst derived from a core–shell NiAl‐LDHs/USY hybrid material has been prepared by the in situ growth of a layered double hydroxides (LDHs) precursor on the surface of USY zeolite crystals. Under the appropriate conditions, the adscititious Ni source interacted chemoselectively with Al species dissolved from the zeolite framework to form a LDHs structure anchored robustly on the surface of zeolite crystals. The dealumination of the low‐silica zeolite and the immobilization of Ni metal species were realized simultaneously in this one‐pot synthesis to afford hierarchical NiAl‐LDHs/USY hybrid composites. The NiII species in these hybrid composites were reduced readily at much lower temperatures than that of bulk NiAl‐LDH, which gave rise to highly dispersed Ni nanoparticles. Meanwhile, the resultant material possessed an excellent mesoporous structure and a high surface area inherited from the USY structure, which led to an excellent hydrogenation rate and activity for the conversion of m‐nitroaniline to m‐phenylenediamine. This unique method could be a promising and general strategy to fabricate desirable hybrid materials for redox catalysis in particular for supported transition metals with similar characteristics to Ni.
Freestanding Nanoengineered [001] Preferentially Oriented TiO2 Nanosheets−Graphene Planarly Aligned Nanohybrids with Enhanced Li‐Storage Properties
Authors: Li Qingwei , Li Yuanyuan , Wang Lei , Ren Xiaochuan , Zhang Jiabao , Liao Zhenhua , Peng Xiang , Gao Biao , Chu Paul K , Huo Kaifu
Published: July 2017

A freestanding film electrode comprising face‐to‐face alternately stacked 2D TiO2 nanosheets and reduced graphene oxide (rGO) is designed and fabricated as a binder‐free anode for lithium‐ion batteries. The ultrathin TiO2 nanosheets, with (001) facets exposed were face‐to‐face hetero‐assembled onto the conductive rGO, allowing Li+ to swiftly diffuse into the TiO2 nanosheets across the (001) facets with the lowest barrier and a short transfer distance. The configuration of this planar‐aligned electrode leads to superior lithium performance, which delivers a large capacity of 132.3 mA h g−1 with a capacity retention of 89 % over 1000 cycles at a high rate of 20 C (1 C=168 mA g−1). This work proves that controlling the arrangement orientation of electrode materials with an anisotropy Li+ diffusion barrier could remarkably improve the electrochemical properties, for promising applications in high‐power energy‐storage devices.
Advances in Stereoselective 1,2‐cisGlycosylation using C‐2 Auxiliaries
Authors: Mensink Rens A. , Boltje Thomas J.
Published: July 2017

The control of stereoselectivity in a glycosylation reaction remains one of the most challenging aspects of oligosaccharide synthesis. Especially the synthesis of 1,2‐cis‐glycosides is challenging and generally applicable methodology to prepare this linkage is needed to standardize oligosaccharide synthesis. This review highlights the recent development of an elegant strategy employing a C‐2 auxiliary to control the anomeric stereoselectivity in glycosylations. The various auxiliaries developed to date, their compatibility with protecting groups and monosaccharide types as well as mechanistic aspects are summarized. Furthermore, the application, advantages and limitations of C‐2 auxiliaries in oligosaccharide synthesis are discussed.
Altering the Coordination of Iron Porphyrins by Ionic Liquid Nanodomains in Mixed Solvent Systems
Authors: Atifi Abderrahman , Ryan Michael D.
Published: July 2017

The solvent environment around iron porphyrin complexes was examined using mixed molecular/RTIL (room temperature ionic liquid) solutions. The formation of nanodomains in these solutions provides different solvation environments for substrates that could have significant impact on their chemical reactivity. Iron porphyrins (Fe(P)), whose properties are sensitive to solvent and ligation changes, were used to probe the molecular/RTIL environment. The addition of RTILs to molecular solvents shifted the redox potentials to more positive values. When there was no ligation change upon reduction, the shift in the E° values were correlated to the Gutmann acceptor number, as was observed for other porphyrins with similar charge changes. As %RTIL approached 100 %, there was insufficient THF to maintain coordination and the E° values were much more dependent upon the %RTIL. In the case of FeIII(P)(Cl), the shifts in the E° values were driven by the release of the chloride ion and its strong attraction to the ionic liquid environment. The spectroscopic properties and distribution of the FeII and FeI species into the RTIL nanodomains were monitored with visible spectroelectrochemistry, 19F NMR and EPR spectroscopy. This investigation shows that coordination and charge delocalization (metal versus ligand) in the metalloporphyrins redox products can be altered by the RTIL fraction in the solvent system, allowing an easy tuning of their chemical reactivity.
A Structurally Characterized CuIII Complex Supported by a Bis(anilido) Ligand and Its Oxidative Catalytic Activity
Authors: Kochem Amélie , Molloy Jennifer K. , Gellon Gisèle , Leconte Nicolas , Philouze Christian , Berthiol Florian , Jarjayes Olivier , Thomas Fabrice
Published: July 2017

Three copper(II) complexes of the (R,R)‐N,N′‐bis(3,5‐di‐tert‐butyl‐2‐aminobenzylidene)‐1,2‐diaminocyclohexane ligand, namely [Cu(NL)], [Cu(NLH)]+ and [Cu(NLH2)]2+, were prepared and structurally characterized. In [Cu(NLH2)]2+ the copper ion lies in an octahedral geometry with the aniline groups coordinated in equatorial positions. In [Cu(NL)] the anilines are deprotonated (anilido moieties) and coordinated to an almost square‐planar metal ion. Complex [Cu(NL)] displays two oxidation waves at E1/2ox, 1=−0.14 V and E1/2ox, 2=0.36 V vs. Fc+/Fc in CH2Cl2. Complex [Cu(NLH2)]2+ displays an irreversible oxidation wave at high potential (1.21 V), but shows a readily accessible and reversible metal‐centered reduction at E1/2red=−0.67 V (CuII/CuI redox couple). Oxidation of [Cu(NL)] by AgSbF6 produces [Cu(NL)](SbF6), which was isolated as single crystals. X‐ray structure analysis discloses a contraction of the coordination sphere by 0.05 Å upon oxidation, supporting a metal‐centered process. Complex [Cu(NL)](SbF6) displays an intense NIR band at 1260 nm corresponding to an anilido‐to‐copper(III) charge transfer transition. This compound slowly evolves in CH2Cl2 solution towards [Cu(NLH)](SbF6), which is a copper(II) complex comprised of both anilido and aniline groups coordinated to the metal center. The copper(III) complex [Cu(NL)](SbF6) is an efficient catalyst for benzyl alcohol oxidation, with 236 TON in 24 h at 298 K, without additives other than oxygen and a base.
Confinement of Reactive Oxygen Species in an Artificial‐Enzyme‐Based Hollow Structure To Eliminate Adverse Effects of Photocatalysis on UV Filters
Authors: Ju Enguo , Dong Kai , Wang Zhenzhen , Zhang Yan , Cao Fangfang , Chen Zhaowei , Pu Fang , Ren Jinsong , Qu Xiaogang
Published: July 2017

Skin cancers caused by UV irradiation have been a major public health problem. One simple and effective way to avoid the above detrimental effects is the use of UV‐protective sunscreens. However, there has been considerable concern with the issue of the production of reactive oxygen species (ROS) through the photodegradation of commercial UV filters. Herein, for the first time, it is reported that the integration of ZnO nanoparticles and CeOx nanoparticles into hollow microspheres (ZnO/CeOx HMS) could provide broad‐spectrum UV protection and scavenge generated ROS under UV irradiation. Benefiting from the cooperative effect of the hollow structure and the antioxidative activity of CeOx, ROS generated under UV irradiation could be confined to a limited space and effectively conversion into nontoxic molecules is catalyzed as a consequence of increased collision frequency. Therefore, both primary, direct UV‐induced damage and secondary ROS toxicity could be greatly reduced.
HMBC‐ und NOESY‐NMR‐Spektroskopie
Authors: Findeisen Matthias , Siehl Hans Ullrich , Berger Stefan
Published: July 2017

In diesem Artikel diskutieren wir zunächst die NMR‐Pulssequenz HMBC (heteronuclear multiple bond correlation) und zeigen ihre Mächtigkeit bei der endgültigen Strukturabsicherung des Naturstoffs Cytisin, dessen 1H‐, 13C‐, COSY‐ und HSQC‐Spektren wir in den ersten beiden Artikeln dieser Serie vorgestellt haben. Danach wird die Physik des NOESY‐Experiments (nuclear Overhauser effect spectroscopy) erläutert und zur Klärung stereochemischer Zuordnung der Protonensignale verwendet. Ein Korrelationsdiagramm zwischen den NOE‐Integralen und den Kernspinabständen bestätigt die korrekte Analyse der vorgestellten Spektren.
Early segmental relaxation abnormalities in hypertrophic cardiomyopathy for differential diagnostic of patients with left ventricular hypertrophy
Authors: Voigt Christian , Münch Julia , Avanesov Maxim , Suling Anna , Witzel Katrin , Lund Gunnar , Patten Monica
Published: July 2017

Background

Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric left ventricular hypertrophy (LVH). However, clinical signs can be subtle and differentiation from other causes of LVH is challenging.

Hypothesis

As diastolic dysfunction (DD) is an early sign in HCM, we aimed to find regional changes in relaxation pattern for differentiation from other entities of LVH.

Methods

In 148 patients (81 HCM, 55 arterial hypertension (AHT), 12 Fabry disease) and 63 healthy controls, relaxation patterns were assessed using regional tissue Doppler imaging. In 42 HCM patients, myocardial mass and fibrosis were quantified by cardiac magnetic resonance imaging and correlated with relaxation parameters.

Results

In HCM the septal to lateral isovolumic relaxation time (s/l IVRT) ratio was higher (1.5 ± 0.4) compared with AHT (1.1 ± 0.2), Fabry disease (1.0 ± 0.1), and controls (1.1 ± 0.2; P < 0.001), showing 77% sensitivity and 79% specificity to discriminate HCM‐related LVH from other entities. The s/l IVRT ratio was independent of global DD in HCM (HCM with DD: 1.5 ± 0.5, n = 52; HCM without DD: 1.5 ± 0.3, n = 29) and remained significantly different from other entities in a subgroup of HCM patients with maximum wall thickness < 20 mm (s/l ratio: 1.5 ± 0.5, n = 28). Regional IVRT did not correlate with the corresponding segmental myocardial mass or amount of fibrosis in cardiac magnetic resonance imaging.

Conclusions

HCM patients show a prolonged septal IVRT irrespective of the extent of LVH and even before developing global DD. The s/l IVRT ratio is significantly higher in HCM compared with AHT or Fabry disease, thus establishing segmental IVRT analysis as a potential parameter for differential diagnosis in LVH.
Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia
Authors: Legros Laurence , Nicolini Franck E. , Etienne Gabriel , Rousselot Philippe , Rea Delphine , Giraudier Stéphane , Guerci‐Bresler Agnès , Huguet Françoise , Gardembas Martine , Escoffre Martine , Ianotto Jean‐Christophe , Noël Marie‐Pierre , Varet Bruno R. , Pagliardini Thomas , Touitou Irit , Morisset Stéphane , Mahon Francois‐Xavier ,   on behalf of the French Intergroup for Chronic Myeloid Leukemias
Published: July 2017

BACKGROUND

Several studies have demonstrated that approximately one‐half of patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR) are able to successfully discontinue therapy. In patients who have a molecular relapse, a DMR is rapidly regained upon treatment re‐initiation.

METHODS

The authors report the results from RE‐STIM, a French observational, multicenter study that evaluated treatment‐free remission (TFR) in 70 patients who re‐attempted TKI discontinuation after a first unsuccessful attempt. After the second TKI discontinuation attempt, the trigger for treatment re‐introduction was the loss of a major molecular response in all patients.

RESULTS

The median follow‐up was 38.3 months (range, 4.7‐117 months), and 45 patients (64.3%) lost a major molecular response after a median time off therapy of 5.3 months (range, 2‐42 months). TFR rates at 12, 24, and 36 months were 48% (95% confidence interval [CI], 37.6%‐61.5%), 42% (95% CI, 31.5%‐55.4%), and 35% (95% CI, 24.4%‐49.4%), respectively. No progression toward advanced‐phase CML occurred, and no efficacy issue was observed upon TKI re‐introduction. In univariate analysis, the speed of molecular relapse after the first TKI discontinuation attempt was the only factor significantly associated with outcome. The TFR rate at 24 months was 72% (95% CI, 48.8%‐100%) in patients who remained in DMR within the first 3 months after the first TKI discontinuation and 36% (95% CI, 25.8%‐51.3%) for others.

CONCLUSIONS

This study is the first to demonstrate that a second TKI discontinuation attempt is safe and that a first failed attempt at discontinuing TKI does not preclude a second successful attempt. Cancer 2017;123:4403‐10. © 2017 American Cancer Society.
Neoadjuvant chemotherapy prior to radical cystectomy for muscle‐invasive bladder cancer with variant histology
Authors: Vetterlein Malte W. , Wankowicz Stephanie A. M. , Seisen Thomas , Lander Richard , Löppenberg Björn , Chun Felix K.‐H. , Menon Mani , Sun Maxine , Barletta Justine A. , Choueiri Toni K. , Bellmunt Joaquim , Trinh Quoc‐Dien , Preston Mark A.
Published: July 2017

BACKGROUND

Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non‐organ‐confined disease and overall survival after radical cystectomy (RC) in patients with histological variants.

METHODS

Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non‐organ‐confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup.

RESULTS

Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08‐0.32 [P<.001]), micropapillary differentiation (OR, 0.30; 95% CI, 0.10‐0.95 [P=.041]), sarcomatoid urothelial carcinoma (OR, 0.40; 95% CI, 0.17‐0.94 [P=.035]), and adenocarcinoma (OR, 0.24; 95% CI, 0.06‐0.91 [P=.035]) were less likely to harbor non‐organ‐confined disease at the time of RC when treated with neoadjuvant chemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33‐0.74 [P=.001]).

CONCLUSIONS

Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non‐organ‐confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non‐organ‐confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346‐55. © 2017 American Cancer Society.
Chronic hepatitis C virus infection and neurocognitive function in adult survivors of childhood cancer
Authors: Studaway Adrienne , Ojha Rohit P. , Brinkman Tara M. , Zhang Nan , Baassiri Malek , Banerjee Pia , Ehrhardt Matthew J. , Srivastava Deokumar , Robison Leslie L. , Hudson Melissa M. , Krull Kevin R.
Published: July 2017

BACKGROUND

Cancer survivors transfused with blood products before reliable screening for hepatitis C virus (HCV) are at risk for infection. This study examined the impact of HCV on neurocognitive function and health‐related quality of life (HRQOL) among adult survivors of childhood cancer.

METHODS

Neurocognitive testing was conducted for 836 adult survivors of childhood cancer (mean age, 35 years [standard deviation, 7.4 years]; time since diagnosis, 29 years [standard deviation, 6.2 years]) who received blood products before universal HCV screening. No differences were observed between confirmed HCV‐seropositive survivors (n = 79) and HCV‐seronegative survivors (n = 757) in the primary diagnosis or neurotoxic therapies. Multivariate regression models were used to compare functional outcomes between seropositive and seronegative survivors.

RESULTS

Compared with seronegative survivors, seropositive survivors demonstrated lower performance on measures of attention (P < .001), processing speed (P = .008), long‐term verbal memory (P = .01), and executive function (P = .001). After adjustments for sex, age at diagnosis, and treatment exposures, seropositive survivors had a higher prevalence of impairment in processing speed (prevalence ratio [PR], 1.3; 95% confidence interval [CI], 1.1‐1.6) and executive functioning (PR, 1.3; 95% CI, 1.1‐1.6). Differences were not associated with the treatment of HCV or the presence of liver cirrhosis. Seropositive survivors reported worse general HRQOL (PR, 1.6; 95% CI, 1.2‐2.1), which was associated with the presence of liver cirrhosis (P = .001).

CONCLUSIONS

Survivors of childhood cancer with a history of HCV infection are at risk for neurocognitive impairment and reduced HRQOL beyond the known risks associated with neurotoxic cancer therapies. Cancer 2017;123:4498‐505. © 2017 American Cancer Society.
Design of a secure and effective medical cyber‐physical system for ubiquitous telemonitoring pregnancy
Authors: Li Guan‐Chen , Chen Chin‐Ling , Chen Hsing‐Chung , Lin Feng , Gu Cheng
Published: July 2017

In recent years, ubiquitous‐based telemedicine has become increasingly popular in many countries; this is a new discipline that can break distance barriers in order to improve access to various medical services. Due to recent progress in telecare services, scientists provided those pregnant women with advanced medical care via medical cyber‐physical systems (MCPS) to achieve eugenics. The MCPS presents a new level of integrated intelligence that is characterized by interaction and coordination of computing processes with physical processes. In an environment of MCPS, security is one of the key objectives for ubiquitous telemonitoring. In this paper, we take advantage of the cloud characteristics and the high efficiency of MCPS to achieve the desired medical monitoring and also to effectively protect pregnancy‐related privacy. We establish a cloud computing platform for all users to access the cloud information at any time in accordance with their own demands. We also used cryptography to design the medical system. Identity‐based combined encryption and signature cryptosystem were proposed as the best ways to ensure the security and privacy of healthcare data in the cloud.
Tuning the Spin Coupling Interactions in the Nitroxide‐Based Bisphenol‐Like Diradicals
Authors: Song Meiyu , Song Xinyu , Bu Yuxiang
Published: July 2017

The intramolecular spin coupling interactions of bisphenol‐like trinary‐bridged diradicals [nitroxide‐(para/meta)phenylene‐X‐phenylene(para/meta)‐nitroxide, X=C=CH2, O, BH, NH and SO2] were explored with an emphasis on the tuning role of the X coupler at the (U)B3LYP/6‐311++G(d,p) level. Our results indicate that all designed trinary‐bridged diradicals featuring a V‐type structure with a bending angle of 104–130° and torsional angles of two phenylene rings being 20–90° exhibit different diradical character and magnetism, depending on the structures and properties of the X bridges. More interestingly, although meta/para‐phenylene supports a ferromagnetic (FM)/antiferromagnetic (AFM) coupling, their combinations by using X as a trinary bridge can mediate spin coupling, but the coupling magnitude strongly depends on X. In general, a para/para or meta/meta combination with X leads to an open‐shell singlet ground state and thus AFM, but the meta/meta combination considerably decreases the spin coupling interaction. In contrast, a para/meta combination with X produces a triplet ground state and FM. Their combination with a single‐electron conjugation end coupler (C=CH2) leads to an inverse coupling regularity. All results can be reasonably explained by the spin alternation rule, molecular structures, and properties. In particular, detailed spin coupling mechanisms are suggested to involve cooperative through‐space and through‐bond pathways with different levels of cooperativity. This is rationalized with the X‐induced bending of the diradicals not only modifying the through‐bond (extended π conjugation) pathway but also provididng a through‐space (face‐to‐face vs. side‐to‐side π–π interaction) possibility for spin coupling, in conjunction with twisting of the phenylene rings. Different contributions of the through‐space and through‐bond couplings are quantitatively distinguished and depend on the structure and property of the X coupler. Clearly, this work reports interesting aspects of the trinary bridged diradicals and also provides important information for the design of molecules for functional magnetic materials and tuning their magnetic properties.
Bifunctionalized Monomers for Surfaces with Controlled Hydrophobicity
Authors: Ben Trad Rawia , El Kout Emna , El Kateb Mejda , Beji Mohammed , Laugier Jean‐Pierre , Godeau Guilhem , Guittard Frédéric , Darmanin Thierry
Published: July 2017

The control of surface wettability is a key parameter for many application fields (materials, biomedical engineering, etc.). In this work, a new and efficient strategy to synthesize monomers suitable for hydrophobic surface elaboration is reported. This original approach allows the preparation of monomers and, as a consequence, surfaces bearing two different substituents by using the Staudinger reductive amination and amidification. Rough conducting polymer films were prepared by electropolymerization. The original surfaces reported here are highly structured surfaces with tunable hydrophobic features. Depending on the grafted chains, the surfaces are hydrophilic (PEDOT‐Benz‐Ph, θ=80 °; PEDOT=poly(3,4‐ethylenedioxythiophene)), hydrophobic (PEDOT‐Benz‐C12, θ=132 °), or even superhydrophobic (PEDOT‐Benz‐F8, θ=152 ° (α=5.0 °, H=0.3 °).
Hydrothermal Synthesis of ZnxNi1−xS Nanosheets for Hybrid Supercapacitor Applications
Authors: Mao Xiaoqing , Wang Weizhi , Wang Zhenghua
Published: July 2017

Nickel‐foam‐supported ZnxNi1−xS nanosheets are synthesized by a two‐step hydrothermal method. The ZnxNi1−xS nanosheets can be considered as the product of the partial substitution of Zn2+ ions by Ni2+ ions in the ZnS lattice. The resulting ZnxNi1−xS/Ni foam can be directly used as an electrode for supercapacitors. It can reach a specific capacitance of 1412 F g−1 at a current density of 1 Ag−1 with 68.0 % capacitance retention at 16 Ag−1. Control experiments show that the electrochemical performances of ZnxNi1−xS nanosheets are much better than those of ZnS and NiS prepared under the same conditions. Furthermore, a hybrid supercapacitor device was assembled by using the ZnxNi1−xS nanosheets as the positive electrode and porous carbon as the negative electrode; the device exhibited high power and energy densities. This study demonstrates that the construction of bimetal sulfides is a strategy to develop high‐performance supercapacitor electrode materials.
Fusing tree‐ring and forest inventory data to infer influences on tree growth
Authors: Evans Margaret E. K. , Falk Donald A. , Arizpe Alexis , Swetnam Tyson L. , Babst Flurin , Holsinger Kent E.
Published: July 2017

Better understanding and prediction of tree growth is important because of the many ecosystem services provided by forests and the uncertainty surrounding how forests will respond to anthropogenic climate change. With the ultimate goal of improving models of forest dynamics, here we construct a statistical model that combines complementary data sources, tree‐ring and forest inventory data. A Bayesian hierarchical model was used to gain inference on the effects of many factors on tree growth—individual tree size, climate, biophysical conditions, stand‐level competitive environment, tree‐level canopy status, and forest management treatments—using both diameter at breast height (dbh) and tree‐ring data. The model consists of two multiple regression models, one each for the two data sources, linked via a constant of proportionality between coefficients that are found in parallel in the two regressions. This model was applied to a data set of ~130 increment cores and ~500 repeat measurements of dbh at a single site in the Jemez Mountains of north‐central New Mexico,USA. The tree‐ring data serve as the only source of information on how annual growth responds to climate variation, whereas both data types inform non‐climatic effects on growth. Inferences from the model included positive effects on growth of seasonal precipitation, wetness index, and height ratio, and negative effects of dbh, seasonal temperature, southerly aspect and radiation, and plot basal area. Climatic effects inferred by the model were confirmed by a dendroclimatic analysis. Combining the two data sources substantially reduced uncertainty about non‐climate fixed effects on radial increments. This demonstrates that forest inventory data measured on many trees, combined with tree‐ring data developed for a small number of trees, can be used to quantify and parse multiple influences on absolute tree growth. We highlight the kinds of research questions that can be addressed by combining the high‐resolution information on climate effects contained in tree rings with the rich tree‐ and stand‐level information found in forest inventories, including projection of tree growth under future climate scenarios, carbon accounting, and investigation of management actions aimed at increasing forest resilience.
Detect and exploit hidden structure in fatty acid signature data
Authors: Bromaghin Jeffrey F. , Budge Suzanne M. , Thiemann Gregory W.
Published: July 2017

Estimates of predator diet composition are essential to our understanding of their ecology. Although several methods of estimating diet are practiced, methods based on biomarkers have become increasingly common. Quantitative fatty acid signature analysis (QFASA) is a popular method that continues to be refined and extended. Quantitative fatty acid signature analysis is based on differences in the signatures of prey types, often species, which are recognized and designated by investigators. Similarly, predator signatures may be structured by known factors such as sex or age class, and the season or region of sample collection. The recognized structure in signature data inherently influences QFASA results in important and typically beneficial ways. However, predator and prey signatures may contain additional, hidden structure that investigators either choose not to incorporate into an analysis or of which they are unaware, being caused by unknown ecological mechanisms. Hidden structure also influences QFASA results, most often negatively. We developed a new method to explore signature data for hidden structure, called divisive magnetic clustering (DIMAC). Our DIMAC approach is based on the same distance measure used in diet estimation, closely linking methods of data exploration and parameter estimation, and it does not require data transformation or distributional assumptions, as do many multivariate ordination methods in common use. We investigated the potential benefits of the DIMAC method to detect and subsequently exploit hidden structure in signature data using two prey signature libraries with quite different characteristics. We found that the existence of hidden structure in prey signatures can increase the confusion between prey types and thereby reduce the accuracy and precision of QFASA diet estimates. Conversely, the detection and exploitation of hidden structure represent a potential opportunity to improve predator diet estimates and may lead to new insights into the ecology of either predator or prey. The DIMAC algorithm is implemented in the R diet estimation package qfasar.
The inflammatory cytokine interferon‐gamma inhibits sortilin‐1 expression in hepatocytes via the JAK/STAT pathway
Authors: Pirault John , Polyzos Konstantinos A. , Petri Marcelo H. , Ketelhuth Daniel F. J. , Bäck Magnus , Hansson Göran K.
Published: July 2017

Sortilin‐1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome‐wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear. Chronic inflammation is a hallmark of atherosclerosis and the absence of regulatory T (Treg) cells is associated with reduced protein expression of sortilin‐1 in the liver. Therefore, we postulated that mediator(s) of inflammation known to be downregulated by Treg cells may modulate sortilin‐1 expression. In this study, we identify interferon‐gamma (IFN‐γ) as the key inflammatory mediator controlling sortilin‐1 levels. In vitro cultures of murine hepatocytes cell line and in silico experiments showed that the transcription factor Signal transducer and activator of transcription 1 was activated and bound to the Sort‐1 gene upon IFN‐γ treatment. This reduced the expression of sortilin‐1, while disrupting the IFN‐γ signaling pathway prevented the effect. These data unravel an intricate mechanism by which inflammation modulates receptors involved in lipoprotein turnover.
IL‐33‐expanded human Vγ9Vδ2 T cells have anti‐lymphoma effect in a mouse tumor model
Authors: Duault Caroline , Betous Delphine , Bezombes Christine , Roga Stéphane , Cayrol Corinne , Girard Jean‐Philippe , Fournié Jean‐Jacques , Poupot Mary
Published: July 2017

From several years, the anticancer effects of Vγ9 T lymphocytes make these cells good candidates for cancer immunotherapies. However, the proved efficacy of γδ Τ cell‐based cancer immunotherapies in some clinical trials was minimized due to the inherent toxicity of IL‐2, which is essential for the combination therapy with Phosphoantigen (PAg). Recently, we showed that IL‐33, a γ chain receptor‐independent cytokine, was able to induce the in vitro proliferation of PAg‐activated Vγ9 T cells, which were fully functional expressing IFN‐γ and TNF‐α and showing in vitro anti‐tumor cytotoxicity. We proposed IL‐33 as an alternative to IL‐2 for Vγ9 T cell‐based cancer immunotherapies, and have therefore evaluated the efficacy of this cytokine in preclinical investigations. This study shows that human Vγ9 T cells are able to proliferate in a mouse model with the combination of PAg and rhIL‐33, and that IL‐33‐expanded Vγ9 T cells can prevent tumor growth in a mouse lymphoma model.
Benzo/Naphtho‐Anellated Dihydro‐1,2‐oxaphosphinines and Ring‐Opening to P‐Tertiary 2‐Phosphanyl‐1,1′‐biaryl‐2‐ol Derivatives – Syntheses and Structures
Authors: Wawrzyniak Piotr , Kindermann Markus K. , Thede Gabriele , Schulzke Carola , Jones Peter G. , Heinicke Joachim W.
Published: July 2017

Reaction of naphthylphenol 1a and phenylnaphthol 1b, respectively, with PCl3 in the presence of ZnCl2 gave mixed benzo‐ and naphtho‐anellated 6‐chloro‐6H‐1,2‐oxaphosphinines 2a and 2b. Treatment with equimolar amounts of tBuLi led to 6‐tBu‐substituted mixed‐anellated oxaphosphinines 3a and 3b, respectively, and subsequent P–O‐ring cleavage with methyllithium and quenching with ClSiMe3 to 2‐trimethylsilyloxy‐biarylphosphanes 4a and 4b. NMR spectra indicated two data sets for 4a but only one for 4b, indicating higher diastereoselectivity in the ring opening of the 1,2‐oxaphosphinine 3b with oxygen in 2‐position of naphthalene and the bulkier tBuMeP‐group at the phenyl ring. Reaction of 2b with o‐anisyllithium (2 equiv.) and ClSiMe3 led to the biarylsilyl ether 5b. Further conversion with (1S)‐camphanoyl chloride gave diastereoisomers of the 2′‐phosphanylbiaryl camphanate 6b. Structures were proven by characteristic multinuclear NMR spectroscopic data and for 2a and 5d by crystal structure analysis. 5b and 6b might be useful candidates for enantiomer separation and asymmetric transition metal catalysis.
A Bis(dipyrrinato) Motif as a Building Block for Polynuclear Rhenium(I) Architectures
Authors: Zhang Yuzhen , Crawley Matthew R. , Hauke Cory E. , Friedman Alan E. , Janik Thomas S. , Cook Timothy R.
Published: July 2017

The coordination of a bis(dipyrrin) ligand (LH2) to Re(CO)5Cl delivers a dirhenium salt that serves as a precursor to a dinuclear phosphine compound or as a component of a metallacycle when combined with 4,4′‐bipyridine (bpy) to furnish a tetranuclear [{(CO)3Re}4L2(bpy)2] complex. The distorted nature of the metallacycle was determined by single‐crystal X‐ray diffraction revealing that the Re‐bpy‐Re edges are twisted by approximately 119° and the Re‐L‐Re edges are twisted by approximately 88° from the idealized rectangular plane. The ReI metallacycle exhibits luminescence (λfluo. = 592 nm; λphos. = 731 nm) in CH2Cl2 at 77 K.
Continuous Platinum‐Mediated Hydrogenation of Refametinib Iodo‐nitroaniline Key Intermediate DIM‐NA: The Combined Challenges of Selectivity and Catalyst Deactivation
Authors: Baramov Todor , Hassfeld Jorma , Gottfried Michael , Bauer Hermann , Herrmann Tanja , Ben Said Mourad , Roggan Stefan
Published: July 2017

The chemoselective, continuous, multistep reduction of iodo‐nitroaromatics in a fixed‐bed hydrogenation reactor has been investigated. This transformation poses challenges upon both the catalyst and process conditions if high yields are to be achieved. First, the stability and selectivity of four flow‐compatible Pt catalysts, Pt(X)/C (X = Fe, V), were investigated by using 1‐iodo‐4‐nitrobenzene as the model substrate. Granular Pt(Fe) on carbon was identified as the most promising candidate. With this catalyst, iodo‐nitroaromatic API (active pharmaceutical ingredient) intermediate DIM‐NA [(2,3‐difluoro‐5‐methoxy‐6‐nitrophenyl)(2‐fluoro‐4‐iodophenyl)amine] could be converted into the corresponding aniline with high selectivity on a preparative scale. UV/Vis spectroscopy was successfully applied for online conversion control, proving to be highly useful for detecting the effects of catalyst deactivation.
Transient electroosmosis of a Maxwell fluid in a rotating microchannel
Authors: Kaushik Prasad , Mandal Shubhadeep , Chakraborty Suman
Published: July 2017

The transient electroosmotic flow of Maxwell fluid in a rotating microchannel is investigated both analytically and numerically. We bring out the complex dynamics of the flow during the transience due to the combination of rotation and rheological effects. We show the regimes of operation under which our analysis holds the most significance. We also shed some light on the volumetric flow rate characteristics as dictated by the underlying flow physics. Mainly we show and analyze the various regimes of operation under which viscoelastic effects actuated by electroosmotic forcing dominate over Coriolis forces and vice versa, which has not been studied before. We also observe that the analytical solution compares well with the numerical solution. We believe that the results from the present study could potentially have far reaching applications in bio‐fluidic microsystems where fluids such as blood, mucus and saliva may be involved.