bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between obesity and clinical outcome in adults with acute myeloid leukemia: A pooled analysis from fourCALGB(alliance) clinical trials
Authors: Castillo Jorge J. , Mulkey Flora , Geyer Susan , Kolitz Jonathan E. , Blum William , Powell Bayard L. , George Stephen L. , Larson Richard A. , Stone Richard M.
Published: November 2015

Obesity has been previously suggested as an adverse prognostic marker in patients with acute leukemia. To evaluate the relationship between obesity and clinical outcome, disease‐free survival (DFS) and overall survival (OS), in patients with acute myelogenous leukemia (AML), including acute promyelocytic leukemia (APL), we performed a pooled analysis of four CALGB (Alliance) clinical trials. Our study included 446 patients with APL from CALGB 9710, and 1,648 patients between 18 and 60 years of age with non‐APL AML from CALGB 9621, 10503, and 19808. Obesity was defined as BMI ≥30 kg/m2. Multivariate Cox proportional‐hazard regression models were fitted for DFS and OS. Obesity was seen in 50% and 38% of APL and non‐APL AML patients, respectively. In APL patients, obesity was associated with worse DFS (HR 1.53, 95% CI 1.03–2.27;P =0.04) and OS (HR 1.72, 95% CI 1.15–2.58;P =0.01) after adjusting for age, sex, performance status, race, ethnicity, treatment arm and baseline white blood cell count. Obesity was not significantly associated with DFS or OS in the non‐APL AML patients. In conclusion, our study indicates that obesity has significant prognostic value for DFS and OS in APL patients, but not for non‐APL AML patients. Am. J. Hematol. 91:199–204, 2016. © 2015 Wiley Periodicals, Inc.
DNAJC6Mutations Associated With Early‐Onset Parkinson's Disease
Authors: Olgiati Simone , Quadri Marialuisa , Fang Mingyan , Rood Janneke P.M.A. , Saute Jonas A. , Chien Hsin Fen , Bouwkamp Christian G. , Graafland Josja , Minneboo Michelle , Breedveld Guido J. , Zhang Jianguo ,   The International Parkinsonism Genetics Network, Verheijen Frans W. , Boon Agnita J.W. , Kievit Anneke J.A. , Jardim Laura Bannach , Mandemakers Wim , Barbosa Egberto Reis , Rieder Carlos R.M. , Leenders Klaus L. , Wang Jun , Bonifati Vincenzo
Published: November 2015

Objective

DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair‐bound within ∼10 years from onset). Here, for the first time, we report DNAJC6 mutations in early‐onset Parkinson's disease (PD).

Methods

The DNAJC6 open reading frame was analyzed in 274 patients with early‐onset sporadic or familial PD. Selected variants were followed up by cosegregation, homozygosity mapping, linkage analysis, whole‐exome sequencing, and protein studies.

Results

We identified two families with different novel homozygous DNAJC6 mutations segregating with PD. In each family, the DNAJC6 mutation was flanked by long runs of homozygosity within highest linkage peaks. Exome sequencing did not detect additional pathogenic variants within the linkage regions. In both families, patients showed severely decreased steady‐state levels of the auxilin protein in fibroblasts. We also identified a sporadic patient carrying two rare noncoding DNAJC6 variants possibly effecting RNA splicing. All these cases fulfilled the criteria for a clinical diagnosis of early‐onset PD, had symptoms onset in the third‐to‐fifth decade, and slow disease progression. Response to dopaminergic therapies was prominent, but, in some patients, limited by psychiatric side effects. The phenotype overlaps that of other monogenic forms of early‐onset PD.

Interpretation

Our findings delineate a novel form of hereditary early‐onset PD. Screening of DNAJC6 is warranted in all patients with early‐onset PD compatible with autosomal recessive inheritance. Our data provide further evidence for the involvement of synaptic vesicles endocytosis and trafficking in PD pathogenesis. Ann Neurol 2016;79:244–256
Hierarchical β‐Mo2C Nanotubes Organized by Ultrathin Nanosheets as a Highly Efficient Electrocatalyst for Hydrogen Production
Authors: Ma Fei‐Xiang , Wu Hao Bin , Xia Bao Yu , Xu Cheng‐Yan , Lou Xiong Wen (David)
Published: November 2015

Production of hydrogen by electrochemical water splitting has been hindered by the high cost of precious metal catalysts, such as Pt, for the hydrogen evolution reaction (HER). In this work, novel hierarchical β‐Mo2C nanotubes constructed from porous nanosheets have been fabricated and investigated as a high‐performance and low‐cost electrocatalyst for HER. An unusual template‐engaged strategy has been utilized to controllably synthesize Mo‐polydopamine nanotubes, which are further converted into hierarchical β‐Mo2C nanotubes by direct carburization at high temperature. Benefitting from several structural advantages including ultrafine primary nanocrystallites, large exposed surface, fast charge transfer, and unique tubular structure, the as‐prepared hierarchical β‐Mo2C nanotubes exhibit excellent electrocatalytic performance for HER with small overpotential in both acidic and basic conditions, as well as remarkable stability.
Siloxane‐modified polyacrylate low‐residual pressure‐sensitive adhesive with high peeling strength
Authors: Li Pengjuan , Nian Fuwei , Zhang Min , Shen Minmin , Dai Yongqiang , Pang Hao , Liao Bing
Published: November 2015

A low‐residual siloxane‐modified polyacrylate pressure‐sensitive adhesive (PSA) with a high peeling strength was prepared by seeded semicontinuous emulsion polymerization. 3‐Glycidyloxypropyltrimethoxysilane was introduced into the acrylic (AC) PSA through a thermal posttreatment method to crosslink with AC. To improve the adhesion properties, a polymeric emulsifier, 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid, was introduced into the system with the conventional emulsifier. Several key polymerization conditions, such as the initiator concentration, mass ratio of soft monomer to hard monomer, the content of polymeric emulsifier, and siloxane dosages were examined in detail. Then, the optimal conditions and a proper preparation process were established. The results show that we achieved not only a low repeeling residue with high tack and peeling strength but also excellent properties of high‐temperature aging resistance and water resistance. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42975.
Preparation and characterization of high MFR polypropylene and polypropylene/poly(ethylene‐co‐propylene) in‐reactor alloys
Authors: Zhang Biao , Fu Zhisheng , Fan Zhiqiang , Phiriyawirut Phairat , Charoenchaidet Sumate
Published: November 2015

In this work, high melt flow rate (MFR) polypropylene (HF‐PP) and polypropylene/poly(ethylene‐co‐propylene) in‐reactor alloys (HF‐PP/EPR) with MFR ≈ 30 g/10 min were synthesized by spherical MgCl2‐supported Ziegler–Natta catalyst with cyclohexylmethyldimethoxysilane (CHMDMS) or dicyclopentyldimethoxysilane (DCPDMS) as external donor (De). The effects of De on polymerization activity, chain structure, mechanical properties, and phase morphology of HF‐PP and HF‐PP/EPR were studied. Adding CHMDMS caused more sensitive change of the polymers MFR with H2 than DCPDMS, and produced PP/EPR alloys containing more random ethylene‐propylene copolymer (r‐EP) and segmented ethylene‐propylene copolymer (s‐EP). CHMDMS also caused formation of s‐EP with higher level of blockiness than DCPDMS. HF‐PP/EPR alloy prepared in the presence of DCPDMS exhibited higher flexural properties but lower impact strength than that prepared with CHMDMS. Toughening efficiency of the rubber phase was nearly the same in the alloys prepared using CHMDMS or DCPDMS as De, but stiffness of the alloy can be improved by using DCPDMS. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42984.
Renewable thermoplastic multiphase systems from dimer fatty acids, with mineral microfillers
Authors: Reulier Marie , Boumbimba Rodrigue Matadi , Rasselet Damien , Avérous Luc
Published: November 2015

Renewable thermoplastic blends based on polyurethane (TPU) and polyamide (DAPA) obtained from dimers of fatty acids were reinforced with mineral microfillers, surface coated calcium carbonate (CaCO3) or high aspect ratio talc (HAR), to prepare different micro‐biocomposites systems. The influence of the nature of the filler, the aspect ratio and the filler content (5, 10, and 15 wt %), for different TPU/DAPA ratios (20/80, 50/50, and 80/20 wt %/wt %), were specifically investigated. Differential scanning calorimetry (DSC) and thermogravimetric analyses were conducted to investigate the thermal properties. DSC analyses showed that the addition of CaCO3 had no influence on the glass transition and the melting temperature of the corresponding composites. Moreover, the morphology and the mechanical properties in the solid state of the different multiphase systems were investigated. SEM observations after tensile tests showed that the best matrix/filler interactions were obtained in the case of the 20/80‐based systems. Uniaxial tensile tests have shown that the addition of HAR or CaCO3 fillers led to a clear increase of the Young modulus. Micromechanical models based on a two‐phase composite approach, including Mori–Tanaka and Davies models were used to describe the dependence of the elastic modulus on the volume fraction of HAR or CaCO3 fillers. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43055.
Connecting learners: The role of biotechnology programme in preparing students for the industry
Authors: Mohd Saruan Nadiah , Sagran Avinash , Fadzil Kamal Solhaimi , Razali Zuliana , Ow Phui San Rebecca , Somasundram Chandran
Published: November 2015

The recent growth of biotechnology requires a wide range of expertise within the industry. Education is the primary platform for students to gain information and knowledge on biotechnology. In Malaysia where biotechnology is relatively new, education programs and courses must be tailored to meet the demands of the industry. A combination of theoretical knowledge as well as practical and industrial training is essential to ensure graduates are prepared for their career in the fields of biotechnology. Results from this study show that university students lack literacy on biotechnology information and access to facilities provided by the universities. This may be a significant contributing factor to the lack of knowledge and information amongst graduates. Furthermore comparative analysis on the biotechnology program in Malaysian universities with that of other countries show the need to restructure the program by offering more specialized courses as well as soft skills and business subjects. This is to meet the demands of the related professionals as well as the various branches that exist in the biotechnology industry. © 2015 by the International Union of Biochemistry and Molecular Biology, 43:460–467, 2015.
Blue genes: An integrative laboratory to differentiate genetic transformation from gene mutation for underclassmen
Authors: Militello Kevin T. , Chang Ming‐Mei , Simon Robert D. , Lazatin Justine C.
Published: November 2015

The ability of students to understand the relationship between genotype and phenotype, and the mechanisms by which genotypes and phenotypes can change is essential for students studying genetics. To this end, we have developed a four‐week laboratory called Blue Genes, which is designed to help novice students discriminate between two mechanisms by which the genetic material can be altered: genetic transformation and gene mutation. In the first week of the laboratory, students incubate a plasmid DNA with calcium chloride‐treated Escherichia coli JM109 cells and observe a phenotype change from ampicillin sensitive to ampicillin resistant and from white color to blue color on plates containing 5‐bromo‐4‐chloro‐3‐indolyl‐β‐D‐galactopyranoside (X‐gal) and isopropyl β‐D‐thiogalactopyranoside (IPTG). Over the course of the next three weeks, students use a battery of approaches including plasmid DNA isolation experiments, restriction maps, and PCR to differentiate between mutation and transformation. The students ultimately come to the conclusion that the changes in phenotypes are due to genetic transformation and not mutation based on the evidence generated over the four‐week period. Pre‐laboratory tests and post‐laboratory tests indicate that this set of exercises is successful in helping students differentiate between transformation and mutation. The laboratory is designed for underclassmen and is a good prerequisite for an apprentice‐based research opportunity, although it is not designed as a class based research experience. Potential modifications and future directions of the laboratory based upon student experiences and assessment are presented. © 2015 by The International Union of Biochemistry and Molecular Biology, 44:55–62, 2016.
Implementing fuzzy logic to simulate a process of inference on sensory stimuli of deaf people in an e‐learning environment
Authors: dos Santos Guimarães Rubens , Strafacci Válter , Tasinaffo Paulo Marcelo
Published: November 2015

A novel approach to education aimed at deaf students, based on computing that performs individualized instruction on the domain of programming languages is presented. This approach is fully implemented and evaluated in an educational application model, called model of Mental Architecture Digitized—AMD. In particular, performs user modeling by dynamically identifying and updating a student's knowledge level of all the concepts of the domain knowledge. The concept of AMD is based on fuzzy cognitive maps (FCMs) that are used to represent the dependences among the domain concepts. AMD uses fuzzy sets to represent a student's knowledge level as a subset of the domain knowledge. Thus, it combines fuzzy theory with the overlay model. Moreover, it employs a novel inference mechanism that dynamically updates user stereotypes using fuzzy sets. It should be noted that the overlay model and stereotypes constitute two widely used methods for user modeling. The gain from this novel combination is significant as a student level of knowledge is represented in a more realistic way by automatically modeling the learning or forgetting process of a student with respect to the FCMs and thus, the system can provide individualized adaptive advice. The transmission and retention of knowledge rests on the cognitive faculty of the concepts linked to it. The repeatability of your applications builds a solid foundation for Education, according to behavioral standards set. This cognitive ability to infer on what we observe and perceive, regarded as intrinsic human beings, does not depend of their physical capacity. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 24:320–330, 2016; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21707
A novel percutaneous coronary intervention technique for chronic total occlusion: Contralateral angiography with a single guiding catheter
Authors: Yoshimachi Fuminobu , Torii Sho , Naito Takayuki
Published: November 2015

We report two successful cases with a new percutaneous coronary intervention (PCI) technique to treat chronic total occlusion (CTO) by using contra‐lateral coronary angiography with a single guiding catheter (GC) safely. Firstly, a GC was inserted into the coronary artery supplying collaterals and a microcatheter was inserted into the distal side of the coronary artery. Then, the GC was retroflexed and engaged in the targeted coronary artery with CTO. While the contra‐lateral coronary artery was visualized by injection through a microcatheter, a guide wire was controlled and passed through the CTO lesion. Two sheaths insertion were necessary to perform contra‐lateral angiography in CTO PCI. This new technique makes it possible to perform safe contra‐lateral angiography with a single sheath and a single GC. It could reduce vascular access complication rates. © 2015 Wiley Periodicals, Inc.
Use of a new low profile Occlutech PLD device for closure of Fontan fenestrations
Authors: De Wolf Daniel , Dessy Hugues , Haas Nikolaus
Published: November 2015

For some higher risk patients, fenestrations are still created in total cavopulmonary connection conduits completing the Fontan circulation for univentricular hearts. If these fenestrations remain patent and hemodynamics are favorable, they are closed to improve oxygenation and exercise tolerance and to decrease the risk of paradoxical emboli. Depending on the type of fenestration, different devices are used. Unfortunately, the search for the ideal device is still ongoing. We propose the first experience with the off‐label use of the new Occlutech paravalvular leak device. This device offers the combination of a small delivery sheath size, high flexibility, less material, and a low profile. The low profile in particular could be an advantage in order to reduce the risk of thrombus formation in the low velocity flow environment of the Fontan circulation. © 2015 Wiley Periodicals, Inc.
Off‐label use of the amplatzer ductal occluder II additional size for percutaneous closure of congenital and acquired coronary fistulae
Authors: Marini Davide , Ferraro Gaetana , Agnoletti Gabriella
Published: November 2015

We report two cases in which congenital and acquired fistulae (CAFs) have been successfully closed by using the Amplatzer Ductal Occluder (ADO) II AS in children. Because of the flexibility, small profile and short length of ADO II AS, this device proved to be an excellent option in case of tortuous and short CAFs with coronary branches next to the fistulous orifice. © 2015 Wiley Periodicals, Inc.
The Role of Steric Effects and Acidity in the Direct Synthesis of iso‐Paraffins from Syngas on Cobalt Zeolite Catalysts
Authors: Subramanian Vijayanand , Zholobenko Vladimir L. , Cheng Kang , Lancelot Christine , Heyte Svetlana , Thuriot Joelle , Paul Sébastien , Ordomsky Vitaly V. , Khodakov Andrei Y.
Published: November 2015

This study focuses on the effects of the localization of Co species, zeolite structure, and acidity on the performance of Co bifunctional catalysts promoted with Pt for the direct synthesis of iso‐paraffins from syngas. ZSM‐5, MOR, and BEA were chosen as zeolites with different structures and pore diameters. The catalysts were prepared either by incipient wetness impregnation or by the mechanical mixing of the zeolite with a conventional silica‐supported Co catalyst. The increase in the pore size and open character of the zeolite structure from ZSM‐5 to BEA resulted in a higher fraction of Co located inside the pores of the catalysts prepared by impregnation. The catalytic performance was affected strongly by the zeolite acidity, pore structure, and Co distribution between the pores and the external surface. The selectivity to short‐chain iso‐paraffins is affected principally by the zeolite acidity, whereas the selectivity to long‐chain branched hydrocarbons mostly depends on steric effects.
One‐Pot Synthesis of Iron‐Containing Nanoreactors with Controllable Catalytic Activity Based on Multichannel Mesoporous Silica
Authors: Wang Haiqing , Li Xiaoming , Xiong Cuirong , Gao Shuying , Wang Jun , Kong Yan
Published: November 2015

We have constructed Fe‐substituted silicate nanotube reactors (Fe–NTRs) through a newly developed one‐step solubilization (OSS) method in which cetyltrimethylammonium bromide and P123 are used as structure‐directing and shape‐controlling agents, respectively, and ferrocene is utilized as iron source by solubilizing inside the hydrophobic inner core of the surfactant micelles. The Fe–NTRs showed regular morphology, highly ordered multichannel mesopores, controllable sizes with lengths changing from 150 nm to 1.2 μm, diameters of approximately 130 nm and pore sizes of approximately 2.7 nm, and iron contents in a range from 0.66 to 1.59 wt %. The OSS strategy is also applicable for other metal‐functioned silicate nanoreactors. The catalytic activity of Fe–NTRs in the direct hydroxylation of phenol can be essentially manipulated by the controllable sizes. The release behavior of reactants reveals that the diffusion control derived from the lengths of Fe–NTR should be responsible for the resultant reactivity.
Propane Dehydrogenation over In2O3–Ga2O3–Al2O3 Mixed Oxides
Authors: Tan Shuai , Kim Seok‐Jhin , Moore Jason S. , Liu Yujun , Dixit Ravindra S. , Pendergast John G. , Sholl David S. , Nair Sankar , Jones Christopher W.
Published: November 2015

A series of ternary mixed metal oxides containing Group III A elements (In, Ga, Al) is prepared by means of an alcoholic co‐precipitation method. Specifically, oxide catalysts with a molar composition of In/Ga/Al=5:15:80, 10:10:80, and 15:5:80 are reported. The chemical composition, redox properties, and catalyst structures are fully characterized, with the results suggesting that the indium, gallium, and aluminum moieties are well‐dispersed in the catalysts. The catalysts are evaluated for propane dehydrogenation (PDH) at 570 and 600 °C under 1 atm total pressure. The most effective catalyst with a composition of In/Ga/Al=5:15:80 provides 17 % conversion and approximately 86 % C3H6 selectivity with an initial activity of 4.6 mmol h−1 gcat−1 and 24.1 μmol h−1 m−2. The intrinsic activity on an active metal (i.e. indium and gallium) basis is approximately 3 times that of the In2O3–Ga2O3 family and approximately 3–9 times that of the In2O3–Al2O3 family. The catalyst deactivates with time on stream, and regeneration tests show that removal of surface coke and recovery of an In2O3 state helps to regain the initial activity, whereas reducing In2O3 domains into In0 does not allow for recovery of the performance. Raman analysis of the carbonaceous species deposited on the catalyst indicates catalysts with higher gallium content give more graphitic carbon, which correlates with higher C3H6 selectivity, whereas catalysts with more disordered coke are associated with lower selectivity. However, higher gallium content causes more coke formation, which leads to faster deactivation. This initial study of this family of mixed oxides suggests that an ideal In/Ga ratio may exist whereby catalyst properties may be optimized.
MOF‐Derived Porous NixFe3‐xO4 Nanotubes with Excellent Performance in Lithium‐Ion Batteries
Authors: Xia Yuan , Wang Beibei , Wang Gang , Liu Xiaojie , Wang Hui
Published: November 2015

Ni–Fe bimetallic oxide nanotubes with a hollow and porous structure were synthesized by using metal‐organic framework (MOF) annealing processes. The Ni/Fe molar ratios in the binary metal oxide were rationally designed. Typically, Ni0.62Fe2.38O4 (called NFO‐0.25) nanotubes with a tube shell of around 10 nm possess a specific surface area of 134.3 m2 g−1 and are composed of nanosized primary particles. The lithium‐ion battery performance of the nanotube anode was evaluated by galvanostatic and rate cycling. In the half‐cell, a high capacity of 1184 mA h g−1 for the NFO‐0.25 anode was maintained at a current density of 0.25 A g−1 after 200 cycles. In addition, the NFO‐0.25/LiCoO2 full‐cell has a reversible charge capacity of about 94 mAh g−1 with a high coulombic efficiency at the same current density. The feature of hollow and porous structures remarkably buffers the volume variation, and provides more active sites for lithiation–delithiation reactions, resulting in excellent lithium‐storage performance.
Supramolecular Protein Immobilization on Lipid Bilayers
Authors: Bosmans Ralph P. G. , Hendriksen Wouter E. , Verheijden Mark , Eelkema Rienk , Jonkheijm Pascal , van Esch Jan H. , Brunsveld Luc
Published: November 2015

Protein immobilization on surfaces, and on lipid bilayers specifically, has great potential in biomolecular and biotechnological research. Of current special interest is the immobilization of proteins using supramolecular noncovalent interactions. This allows for a reversible immobilization and obviates the use of harsh ligation conditions that could denature fragile proteins. In the work presented here, reversible supramolecular immobilization of proteins on lipid bilayer surfaces was achieved by using the host–guest interaction of the macrocyclic molecule cucurbit[8]uril. A fluorescent protein was successfully immobilized on the lipid bilayer by making use of the property of cucurbit[8]uril to host together a methylviologen and the indole of a tryptophan positioned on the N‐terminal of the protein. The supramolecular complex was anchored to the bilayer through a cholesterol moiety that was attached to the methylviologen tethered with a small polyethylene glycol spacer. Protein immobilization studies using a quartz crystal microbalance (QCM) showed the assembly of the supramolecular complexes on the bilayer. Specific immobilization through the protein N‐terminus is more efficient than through protein side‐chain events. Reversible surface release of the proteins could be achieved by washing with cucurbit[8]uril or buffer alone. The described system shows the potential of supramolecular assembly of proteins and provides a method for site‐specific protein immobilization under mild conditions in a reversible manner.
Ab Initio Molecular Dynamics with Explicit Solvent Reveals a Two‐Step Pathway in the Frustrated Lewis Pair Reaction
Authors: Pu Maoping , Privalov Timofei
Published: November 2015

The role solvent plays in reactions involving frustrated Lewis pairs (FLPs)—for example, the stoichiometric mixture of a bulky Lewis acid and a bulky Lewis base—still remains largely unexplored at the molecular level. For a reaction of the phosphorus/boron FLP and dissolved CO2 gas, first principles (Born–Oppenheimer) molecular dynamics with explicit solvent reveals a hitherto unknown two‐step reaction pathway—one that complements the concerted (one‐step) mechanism known from the minimum‐energy‐path calculations. The rationalization of the discovered reaction pathway—that is, the stepwise formation of PC and OB bonds—is that the environment (typical organic solvents) stabilizes an intermediate which results from nucleophilic attack of the phosphorus Lewis base on CO2. This finding is significant because presently the concerted reaction‐path paradigm predominates in the rationalization of FLP reactivity. Herein we point out how to attain experimental proof of our results.
Deciphering a 20‐Year‐Old Conundrum: The Mechanisms of Reduction by the Water/Amine/SmI2 Mixture
Authors: Maity Sandeepan , Hoz Shmaryahu
Published: November 2015

The reaction of SmI2 with the substrates 3‐methyl‐2‐butanone, benzyl chloride, p‐cyanobenzyl chloride, and anthracene were studied in the presence of water and an amine. In all cases, the water content versus rate profile shows a maximum at around 0.2 M H2O. The rate versus amine content profile shows in all cases, except for benzyl chloride, saturation behavior, which is typical of a change in the identity of the rate‐determining step. The mechanism that is in agreement with the observed data is that electron transfer occurs in the first step. With substrates that are not very electrophilic, the intermediate radical anions lose the added electron back to samarium(III) relatively quickly and the reaction cannot progress efficiently. However, in a mixture of water/amine, the amine deprotonates a molecule of water coordinated to samarium(III). The negatively charged hydroxide, which is coordinated to samarium(III), reduces its electrophilicity, and therefore, lowers the rate of back electron transfer, which allows the reaction to progress. In the case of benzyl chloride, in which electron transfer is rate determining, deprotonation by the amine is coupled to the electron‐transfer step.
INES – An Interface Between Experiments and Simulation to Support the Development of Robust Process Designs
Authors: Asprion Norbert , Benfer Regina , Blagov Sergej , Böttcher Roger , Bortz Michael , Berezhnyi Maksym , Burger Jakob , Harbou Erik von , Küfer Karl‐Heinz , Hasse Hans
Published: November 2015

The development of chemical processes is based on both experiments and process simulations. Data evaluation and reconciliation, model development and validation, and design of experiments are essential steps in this procedure. The different tools and approaches available are usually not supported in an integrated way in the process developer's workflow. Therefore, a framework for process design was created and integrated in a tool box which supports process design comprehensively. It contains methods for data selection and reconciliation, sensitivity analysis, model validation and model adjustment.
Cu2S/ZnS Heterostructured Nanorods: Cation Exchange vs. Solution–Liquid–Solid‐like Growth
Authors: Zhai You , Shim Moonsub
Published: November 2015

Cu2S/ZnS heterostructured nanorods (HNRs) with uncommon morphologies are achieved through single‐pot and multi‐batch synthetic strategies. In both cases, Cu2S NRs form first, which then undergo partial cation exchange and solution–liquid–solid (SLS)‐like growth catalyzed by the remaining Cu2S parts of the NRs. The location and the volume of ZnS achieved through partial cation exchange control the size of the Cu2S catalysts, which in turn determine whether tapered rod–rod, body/tail, or barbell‐like structure results from subsequent SLS‐like growth. Concurrent cation exchange can sometimes cause Cu2S catalysts to be lost during SLS‐like growth, leading to further diversity in achievable morphologies of Cu2S/ZnS HNRs. Additional insights are gained on how parameters such as Zn precursor, ligand choice, and concentration alter cation exchange and SLS‐like growth steps.
Immunoproteasomes edit tumors, which then escapes immune recognition
Authors: Joyce Sebastian
Published: November 2015

In 1985, John Monaco—the discoverer of LMP‐2 and ‐7, the inducible components of the immunoproteasome—asked his advanced immunology class as to why the MHC region contained not only structural genes, but several others as well, whose functions were then unknown. As we drew a blank, he quipped: perchance because many of the MHC genes are induced by IFN‐γ! The ensuing three decades have witnessed the unveiling of the profound fundamental and clinical implications of that classroom tête–à–tête. Amongst its multitudinous effects, IFN‐γ induces genes enhancing antigen processing and presentation to T cells; such as those encoding cellular proteases and activators of proteases. In this issue, Keller et al. [Eur. J. Immunol. 2015. 45: 3257–3268] demonstrate that the limited success of MART‐1/Melan‐A‐targeted immunotherapy in melanoma patients could be due to inefficient MART‐126—35 presentation, owing to the proteolytic activities of IFN‐γ‐inducible β2i/MECL‐1, proteasome activator 28 (PA28), and endoplasmic reticulum‐associated aminopeptidase‐associated with antigen processing (ERAP). Specifically, whilst β2i and PA28 impede MART‐126—35 liberation from its precursor protein, ERAP‐1 degrades this epitope. Hence, critical to effective cancer immunotherapy is deep knowledge of T‐cell‐targeted tumor antigens and how cellular proteases generate protective epitope(s) from them, or destroy them.
Synthesis, Structure, and Magnetic Properties of Phosphinate‐Bridged Hexanuclear FeIII Complexes Containing Two Butterfly‐Shaped Fe3O Cores
Authors: Goura Joydeb , Oyarzabal Itziar , Colacio Enrique , Chandrasekhar Vadapalli
Published: November 2015

The reaction of FeIII salts with 1,1,2,3,3‐pentamethyltrimethylenephosphinic acid [cycPO2H] or dicyclohexylphosphinic acid [(C6H11)2PO2H] along with pivalic acid in the presence of triethylamine leads to the formation of two hexanuclear iron(III) clusters: [FeIII6(μ3‐O)2(μ‐OH)2(μ‐cycPO2)6(μ‐tBuCO2)6(η1‐tBuCO2H)2]·4CH3CN·3CH2Cl2 (1) and [FeIII6(μ3‐O)2(μ‐OH)2{μ‐(C6H11)2PO2}6(μ‐tBuCO2)6(η1‐OH2)2]·2CH3CN·CH2Cl2 (2). These complexes are made up of two butterfly‐shaped {FeIII3O} subunits that are joined to each other by two bridging phosphinate ligands. In addition, the formation of 1 and 2 is assisted by μ3‐O, μ‐OH, and pivalate ligands. Variable‐temperature magnetic susceptibility measurements of complexes 1 and 2 reveal medium to strong antiferromagnetic interactions between the FeIII ions inside the Fe3O subunits and weak inter‐trinuclear antiferromagnetic interactions through the bridging phosphinate ligands. The triangular topology of the Fe3O subunits gives rise to competing antiferromagnetic interactions and spin frustration. The different relative magnitudes of the competing interactions leads to S = 5/2 and S = 1/2 ground spin states for the Fe3O subunits in 1 and 2, respectively.
Exploring the Solid‐Phase Synthesis of ­Sulfotyrosine Peptides
Authors: Vale Nuno , Carvalho Veloso Rita , Gomes Paula
Published: November 2015

Tyrosine sulfation is a common post‐translational modification operative in many biological processes, including hemostasis and intracellular trafficking. However, the precise structural and functional role of sulfotyrosine residues is not fully understood, so there is a demand for further detailed studies on the role of tyrosine sulfation in biochemical processes. Unfortunately, studies on the biological roles of tyrosine sulfation are hampered by difficulties in gaining access to large quantities of high‐purity and homogeneous sulfoproteins and sulfopeptides. This, however, may be addressed by appropriate solid‐phase peptide synthesis strategies, and these constitute the core subject of this review. An overview of efficient approaches to the synthesis of sulfopeptides and their associated pros and cons is presented.
Pd/C‐Catalyzed Alkylation of Heterocyclic Nucleophiles with Alcohols through the “Borrowing Hydrogen” Process
Authors: Putra Anggi Eka , Oe Yohei , Ohta Tetsuo
Published: November 2015

The alkylation of heterocyclic compounds is important for the synthesis of various biologically active compounds. In this paper, we present the development of a Pd/C‐catalyzed alkylation of heterocyclic compounds using alcohols as the alkylating agents. This method gives the corresponding alkylated heterocyclic compounds in high yields (up to 99 %). The commercially available catalyst can be recovered and reused five times without significant loss of catalytic efficiency, and the turnover number (TON) was as high as 900. Moreover, the reaction could be scaled up.
Breaking and Making of Rings: A Method for the Preparation of 4‐Quinolone‐3‐carb­oxylic Acid Amides and the Expensive Drug Ivacaftor
Authors: Vasudevan N. , Jachak Gorakhnath R. , Reddy D. Srinivasa
Published: November 2015

A simple and convenient method to access 4‐quinolone‐3‐carboxylic acid amides from indole‐3‐acetic acid amides through one‐pot oxidative cleavage of the indole ring followed by condensation (Witkop–Winterfeldt type oxidation) was explored. The scope of the method was confirmed with more than 20 examples and was successfully applied to the synthesis of the drug Ivacaftor, the most expensive drug on the market.
Copper‐Catalysed Cascade Synthesis of Imidazolidine–Benzothiazole and Imid­azolidine–Tetrazole Hybrid Heterocycles from Bis‐thioureas by a Desulfurisation Strategy
Authors: Ganesh Majji , Sahoo Santosh K. , Khatun Nilufa , Patel Bhisma K.
Published: November 2015

The in situ generated bis‐thioureas obtained by treating aryl/alkyl isothiocyanates with aliphatic 1,2‐diamines, upon treatment with CuI or CuII salts, depending on their quantity and the reaction conditions, furnished either imidazolidinecarbothioamide (ImCAT) or imidazolidine–benzothiazole (ImBT) hybrid molecules. The same reactions in the presence of sodium azide yielded imidazolidine–tetrazoles (ImTets). The products were obtained in good yields at room temperature with all these processes taking place in a single pot. This is a perfect illustration of Cu salts serving as both desulfurising as well as C–H activating agents at ambient temperature.
Rapid Access to Polyfunctionalized 3,4‐Dihydroquinazolinones through a Sequential N‐Acyliminium Ion Mannich Reaction Cascade
Authors: Sawant Rajiv T. , Stevens Marc Y. , Odell Luke R.
Published: November 2015

A microwave‐promoted one‐pot, three‐component sequential cyclization‐Mannich reaction of unactivated ketones, o‐formyl carbamates and primary amines has been developed. Cyclic N‐acyliminium ions are generated in situ from the carbamate and amine starting materials. This metal‐free cascade protocol provides rapid access to structurally diverse 3,4‐dihydroquinazolinones in good to excellent yields with high regioselectivity for the terminal methyl group, in the case of unsymmetrical methyl alkyl ketones. Key features of the developed protocol include its operational simplicity, ease of product purification, and wide functional group tolerance.
Frequency of full, partial and no recovery from subsyndromal deliriumin older hospital inpatients
Authors: Cole Martin G. , Bailey Robert , Bonnycastle Michael , McCusker Jane , Fung Shek , Ciampi Antonio , Belzile Eric
Published: November 2015

Objectives

To determine the frequencies of full, partial and no recovery from subsyndromal delirium (SSD) in older hospital inpatients. A secondary objective was to compare the recovery status of patients with SSD or delirium.

Methods

SSD was defined as acute onset of one or more Confusion Assessment Method core symptoms of delirium (fluctuation, inattention, disorganized thinking and altered level of consciousness) not meeting criteria for delirium and not progressing to delirium. The recovery status of medical or surgical inpatients aged 65 and older with SSD was assessed approximately 1 and 3 months after enrolment. Primary outcome categories were full recovery (no core symptoms of delirium), partial recovery (presence of one or more core symptoms but fewer symptoms than at enrolment), no recovery (same number of core symptoms as at enrolment) or death. Nominal logistic regression was used to compare the recovery status of patients with SSD or delirium.

Results

Twenty‐eight patients with SSD were enrolled. At the first follow‐up, the frequencies of full, partial and no recovery and death were 40%, 12%, 32% and 16%, respectively; at the second follow‐up, the frequencies were 54%, 8%, 21% and 17%, respectively. The frequency of full recovery was much higher in patients with SSD than delirium.

Conclusion

Small study sample size notwithstanding, the majority (54%) of patients with SSD recovered fully, but a substantial proportion (29%) had a protracted course. It may be important to monitor the longer‐term course of SSD and develop strategies to ensure full recovery in all patients. Copyright © 2015 John Wiley & Sons, Ltd.
Surface heparin treatment of the decellularized porcine heart valve: Effect on tissue calcification
Authors: Yang Min , Lin Yang‐Hua , Shi Wei‐Ping , Shi Hong‐Can , Gu Y. John , Shu Yu‐Sheng
Published: November 2015

Tissue calcification is a major cause of failure of bioprosthetic heart valves. Aim of this study was to examine whether surface heparin treatment of the decellularized porcine heart valve reduces tissue calcification. Fresh porcine aortic heart valves were dissected as tissue discs and divided into four groups. Group A: controls without treatment, Group B: decellularization only, Group C: decellularization and glutaraldehyde cross‐linking, Group D: decellularization and glutaraldehyde cross‐linking followed by surface heparin treatment. After implantation in New Zealand White rabbits for 60 days, the explanted heart valve discs from the different study groups underwent a series of histological examinations as well as determination of calcium content by the methyl thyme phenol blue colorimetric method. Results of the explanted heart valve discs for the Von Kossa staining demonstrated that in Group A the heart valve tissue was the most severely stained with black color, whereas in Group D there was hardly any area that was stained black after implantation indicating the least tissue calcification. Furthermore, the inflammatory cells identified by the Hematoxylin‐eosin staining appeared to be the least in Group D. The average tissue calcium content was highest in Group A (0.197 ± 0.115 μmol mg−1), modest in Group B (0.113 ± 0.041 μmol mg−1), and Group C (0.089 ± 0.049 μmol mg−1), and the lowest in Group D (0.019 ± 0.019 μmol mg−1, p < 0.05). These results suggest that surface heparin treatment tends to reduce tissue calcification of the dellellularized porcine heart valve in a rabbit intramuscular implantation model. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 400–405, 2017.
Suppression of RAD21 Induces Senescence of MDA‐MB‐231 Human Breast Cancer Cells Through RB1 Pathway Activation Via c‐Myc Downregulation
Authors: Zhu Shan , Zhao Li , Li Yueyang , Hou Pingfu , Yao Ruosi , Tan Jiang , Liu Dongxu , Han Liping , Huang Baiqu , Lu Jun , Zhang Yu
Published: November 2015

Cellular senescence impedes cancer progression by limiting uncontrolled cell proliferation. To identify new genetic events controlling senescence, we performed a small interfering RNA screening human cancer cells and identified a number of targets potentially involved in senescence of MDA‐MB‐231 human breast cancer cells. Importantly, we showed that knockdown of RAD21 resulted in the appearance of several senescent markers, including enhanced senescence‐associated β‐galactosidase activity and heterochromatin focus formation, as well as elevated p21 protein levels and RB1 pathway activation. Further biochemical analyses revealed that RAD21 knockdown led to the downregulation of c‐Myc and its targets, including CDK4, a negative regulator of RB1, and blockedRB1 phosphorylation (pRB1), and the RB1‐mediated transcriptional repression of E2F. Moreover, c‐Myc downregulation was partially mediated by proteasome‐dependent degradation within promyelocytic leukemia (PML) nuclear bodies, which were found to be highly abundant during RAD21 knockdown‐induced senescence. Exogenous c‐Myc reconstitution rescued cells from RAD21 silencing‐induced senescence. Altogether, data arising from this study implicate a novel function of RAD21 in cellular senescence in MDA‐MB‐231 cells that is mainly dependent onRB1 pathway activation via c‐Myc downregulation. J. Cell. Biochem. 117: 1359–1369, 2016. © 2015 Wiley Periodicals, Inc.
A Doubling Construction for 3‐Uniform Friendship Hypergraphs with the Universal Pairs Property
Authors: Cohen Nathann
Published: November 2015

In this note, we present a simple doubling construction for 3‐uniform friendship hypergraphs which generalizes the cubeconstructed hypergraphs from another study (L. Jørgensen and A. Sillasen, J Combin Designs (2014)). As a by‐product, we build point‐transitive 3‐uniform friendship hypergraphs of sizes and for all .
Incorporating metacognition into morbidity and mortality rounds: The next frontier in quality improvement
Authors: Katz David , Detsky Allan S.
Published: November 2015

This Perspective proposes the introduction of metacognition (thinking about thinking) into the existing format of hospital‐based morbidity and mortality rounds. It is placed in the context of historical movements to advance quality improvement by expanding the spectrum of the causes of medical error from systems‐based issues to flawed human decision‐making capabilities. We suggest that the current approach that focuses on systems‐based issues can be improved by exploiting the opportunities to educate physicians about predictable errors committed by reliance on cognitive heuristics. In addition, because the field of educating clinicians about cognitive heuristics has shown mixed results, this proposal represents fertile ground for further research. Educating clinicians about cognitive heuristics may improve metacognition and perhaps be the next frontier in quality improvement. Journal of Hospital Medicine 2016;11:120–122. © 2015 Society of Hospital Medicine
Noninvasive measurement of lower extremity muscle oxygen extraction fraction under cuff compression paradigm
Authors: Wang Chengyan , Zhang Rui , Zhang Xiaodong , Wang He , Zhao Kai , Jin Lixin , Zhang Jue , Wang Xiaoying , Fang Jing
Published: November 2015

Background

To demonstrate the feasibility of using a susceptibility‐based MRI technique with asymmetric spin‐echo (ASE) sequence to assess the lower extremity muscle oxygen extraction fraction (OEF) alternations under cuff compression paradigm.

Methods

Approved by the local institutional human study committee, nine healthy young volunteers participated in this study. All the ASE scans were conducted using a 3 Tesla clinical MRI scanner during resting state (pre), 1–3 min (post1) and 3–5 min (post2) after a pressure of 50 mmHg above individual systolic blood pressure imposed on the thigh. Moreover, near‐infrared spectroscopy (NIRS) measurements were performed on the same day under the same cuff compression protocol to verify the accuracy of this susceptibility‐based method.

Results

In all volunteers, the mean MRI based OEF in gastrocnemius (GAS) muscle increased significantly from 0.28 ± 0.02 (pre) to 0.31 ± 0.03 (post1, P < 0.05) and 0.31 ± 0.03 (post2, P < 0.05). In addition, mean OEF in soleus (SOL) muscle went up from 0.31 ± 0.01 (pre) to 0.33 ± 0.03 (post1, P = 0.14) and 0.37 ± 0.04 (post2, P < 0.05). For comparison, NIRS measured 1‐%HbO2 (percentage of deoxyhemoglobin concentration within total hemoglobin) in GAS rose significantly from 0.29 ± 0.03 (pre) to 0.31 ± 0.04 (post1, P < 0.05) and 0.31 ± 0.04 (post2, P < 0.05), which confirmed the accuracy of the MRI‐based OEF.

Conclusion

This susceptibility‐based OEF quantification technique together with cuff compression paradigm could provide a noninvasive, quantifiable and effective tool for measuring skeletal muscle oxygenation. J. Magn. Reson. Imaging 2016;43:1148–1158.
Good relationships at work: The effects of Leader–Member Exchange and Team–Member Exchange on psychological empowerment, emotional exhaustion, and depression
Authors: Schermuly Carsten C. , Meyer Bertolt
Published: November 2015

Emotional exhaustion and depression pose a threat to employees' psychological health. Social relationships at work are important potential buffers against these threats, but the corresponding psychological processes are still unclear. We propose that the subjective experience of high‐quality relationships with supervisors (i.e., Leader–Member Exchange [LMX]) is one of the protective factors against psychological health issues at work and that this effect is mediated by psychological empowerment. We tested these assumptions with two studies (one cross‐sectional and one time lagged) on diverse samples of employees from different organizations. The first study employed emotional exhaustion as the outcome measure; the second used depression. Results from both studies support the proposed process by showing that LMX positively affects empowerment, which negatively affects emotional exhaustion (Study 1) and depression (Study 2). Additionally, Study 2 also showed that Team–Member Exchange is as important as LMX for preventing psychological health issues among employees. Copyright © 2015 John Wiley & Sons, Ltd.