bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple order model migration and optimal model selection for online glucose prediction in Type 1 diabetes
Authors: Zhao Hong , Zhao Chunhui , Yu Chengxia , Dassau Eyal
Published: September 2017

To address the problem of insufficient available modeling data for glucose prediction, as well as modeling burden, a model migration method was developed in a previous work to quickly transfer an old model to a new subject using a simple parameter adjustment. However, this method, which is referred to as first‐order model migration (FOMM), only considers a single order for each exogenous input, and may not produce an optimal model structure for accurate prediction. To overcome this problem, a multiple order model migration (MOMM) algorithm is proposed in this study. For different numbers of modeling samples, including glucose and two exogenous inputs (meal and insulin), the optimal modeling method may be different, and therefore, must be properly determined for each modeling scenario. First, the optimal model order is determined for each input and a multiple order prediction model is used. Then, a MOMM algorithm is developed based on particle swarm optimization (PSO) to simultaneously revise multiple parameters. The multiple order parameters of each input in the old model are quickly customized so that the revised model can be used for new subjects with desirable prediction accuracy. In particular, the influence of the number of modeling samples is analysed to check the applicability of different methods; this analysis determines the appropriate selection guidelines for the optimal model in response to different data sizes. The proposed method was evaluated using thirty in silico subjects and clinical data from seven individuals with Type 1 diabetes mellitus (DM). Overall, the MOMM algorithm presented superior results when the time period for collecting the samples was larger than 10 h (50 samples). In particular, the size of the modeling samples was separated into three different regions by evaluating the glucose prediction performance and the comparison between different algorithms for both in silico and clinical subjects. In Region I, the FOMM method achieves the best performance. In Region II, the MOMM method should be used and the prediction accuracy is superior in Region II in general. With enough samples (Region III), the subject‐dependent model (SM) algorithm can be chosen. The MOMM algorithm is demonstrated to be able to transfer models for new subjects with improved model structure. © 2017 American Institute of Chemical Engineers AIChE J, 64: 822–834, 2018
Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae
Authors: Eppley Sarah , Hopkin Robert J. , Mendelsohn Bryce , Slavotinek Anne M.
Published: September 2017

We present two new cases of Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy, in sisters aged 13 and 11 years who both had compound heterozygous mutations in DDX11. After exclusion of Fanconi anemia, Bloom syndrome and Nijmegen breakage syndrome, whole exome sequencing revealed two novel variants—c.1523T>G, predicting (p.Leu508Arg) and c.1949‐1G>A (IVS19‐1G>A), that were confirmed with Sanger sequencing in both affected individuals. DDX11 encodes an iron‐sulfur‐containing DNA helicase, and mutations in this gene have been reported in the five WABS cases previously identified to date. The sisters reported here display the distinguishing clinical features of WABS: pre‐ and post‐natal growth restriction, microcephaly, intellectual disability, sensorineural hearing loss with cochlear abnormalities, and facial dysmorphic features. In addition, our cases had early menarche at 8 and 10 years of age, bilateral small thumbs, and the younger, more severely affected sister had small fibulae. These findings broaden the WABS phenotype and the limb malformations demonstrate further clinical overlap with Fanconi anemia and other cohesinopathies, such as Roberts Syndrome.
Accuracy of the smaller superior mesenteric vein sign for the detection of acute superior mesenteric artery occlusion
Authors: Nakano Takaaki , Ito Toshitaka , Takei Tetsuhiro , Takemoto Masaaki
Published: September 2017

Aims

The smaller superior mesenteric vein (SMV) sign is a well‐known computed tomography (CT) parameter for acute superior mesenteric artery (SMA) occlusion. This CT sign is potentially beneficial for the early diagnosis of acute SMA occlusion; however, few reports have documented this sign. The present study aimed to determine the accuracy of the smaller SMV sign for the detection of acute SMA occlusion.

Methods

We retrospectively reviewed CT images from 20 patients with acute SMA occlusion and 1,216 controls. We measured the external diameters of the SMV and SMA, and calculated the SMV/SMA diameter ratio. A ratio ≤1 indicated a positive smaller SMV sign.

Results

Of the 20 patients, 14 had the smaller SMV sign, whereas of the 1,216 controls, 88 had the smaller SMV sign. Of the 88 controls with a positive sign, 79 had apparent reasons for the decreased flow in the SMA and nine patients had no reason for the decreased flow. The sensitivity and specificity of the smaller SMV sign for acute SMA occlusion were 70% and 99.2%, respectively.

Conclusion

The smaller SMV sign is an accurate and important CT parameter for the detection of acute SMA occlusion.
Eine wasserhaltige Organokaliumverbindung basierend auf Bis(4,6‐tert‐Butylbenzoxazol‐2‐yl)methanid und ihre unerwartete Hydrolysebeständigkeit
Authors: Koehne Ingo , Bachmann Sebastian , Herbst‐Irmer Regine , Stalke Dietmar
Published: September 2017

Auf Grundlage des sterisch anspruchsvollen Ligandensystems Bis(4,6‐tBu‐benzoxazol‐2‐yl)methan konnte mit der wasserhaltigen Organokaliumverbindung [(18‐Krone‐6)K{(4,6‐tBu‐OCNC6H2)2CH}⋅H2O] (2) ein einzigartiges Beispiel einer reaktiven, wasserbeständigen Organokaliumverbindung synthetisiert werden. Darüber hinaus ist 2 ein seltener Vertreter eines Metallkomplexes, in dem ein Bis(benzoxazol‐2‐yl)methanid eine ausschließliche O‐Koordination zu einem Metallion zeigt. Verbindung 2 wurde vollständig anhand ihrer Festkörperstruktur charakterisiert. Zusätzlich wurde sein Verhalten in Lösung durch DOSY‐NMR‐ und durch NMR‐Titrationsexperimente beschrieben. Letztere zeigten eine vollständige Protonierung des Komplexes erst nach der Zugabe von 114 Äquivalenten Wasser und einer Reaktionszeit von sieben Tagen.
Reducing the Charge Carrier Transport Barrier in Functionally Layer‐Graded Electrodes
Authors: Zhang Yanyan , Malyi Oleksandr I. , Tang Yuxin , Wei Jiaqi , Zhu Zhiqiang , Xia Huarong , Li Wenlong , Guo Jia , Zhou Xinran , Chen Zhong , Persson Clas , Chen Xiaodong
Published: September 2017

Lithium‐ion batteries (LIBs) are primary energy storage devices to power consumer electronics and electric vehicles, but their capacity is dramatically decreased at ultrahigh charging/discharging rates. This mainly originates from a high Li‐ion/electron transport barrier within a traditional electrode, resulting in reaction polarization issues. To address this limitation, a functionally layer‐graded electrode was designed and fabricated to decrease the charge carrier transport barrier within the electrode. As a proof‐of‐concept, functionally layer‐graded electrodes composing of TiO2(B) and reduced graphene oxide (RGO) exhibit a remarkable capacity of 128 mAh g−1 at a high charging/discharging rate of 20 C (6.7 A g−1), which is much higher than that of a traditionally homogeneous electrode (74 mAh g−1) with the same composition. This is evidenced by the improvement of effective Li ion diffusivity as well as electronic conductivity in the functionally layer‐graded electrodes.
Structural Snapshots of α‐1,3‐Galactosyltransferase with Native Substrates: Insight into the Catalytic Mechanism of Retaining Glycosyltransferases
Authors: Albesa‐Jové David , Sainz‐Polo M. Ángela , Marina Alberto , Guerin Marcelo E.
Published: September 2017

Glycosyltransferases (GTs) are a key family of enzymes that catalyze the synthesis of glycosidic bonds in all living organisms. The reaction involves the transfer of a glycosyl moiety and can proceed with retention or inversion of the anomeric configuration. To date, the catalytic mechanism of retaining GTs is a topic of great controversy, particularly for those enzymes containing a putative nucleophilic residue in the active site, for which the occurrence of a double‐displacement mechanism has been suggested. We report native ternary complexes of the retaining glycosyltransferase α‐1,3‐galactosyltransferase (α3GalT) from Bos taurus, which contains such a nucleophile in the active site, in a productive mode for catalysis in the presence of its sugar donor UDP‐Gal, the acceptor substrate lactose, and the divalent cation cofactor. This new experimental evidence supports the occurrence of a front‐side substrate‐assisted SNi‐type reaction for α3GalT, and suggests a conserved common catalytic mechanism among retaining GTs.
Asymmetric Intermolecular Heck Reaction of Propargylic Acetates and Cycloalkenes to Access Fused Cyclobutenes
Authors: Jiao Zhiwei , Shi Qi , Zhou Jianrong Steve
Published: September 2017

An asymmetric Heck annulation of propargylic acetates with several types of cyclic olefins affords highly strained cyclobutenes in high enantioselectivity.
An Epitope‐Imprinted Biointerface with Dynamic Bioactivity for Modulating Cell–Biomaterial Interactions
Authors: Pan Guoqing , Shinde Sudhirkumar , Yeung Sing Yee , Jakštaitė Miglė , Li Qianjin , Wingren Anette Gjörloff , Sellergren Börje
Published: September 2017

In this study, an epitope‐imprinting strategy was employed for the dynamic display of bioactive ligands on a material interface. An imprinted surface was initially designed to exhibit specific affinity towards a short peptide (i.e., the epitope). This surface was subsequently used to anchor an epitope‐tagged cell‐adhesive peptide ligand (RGD: Arg‐Gly‐Asp). Owing to reversible epitope‐binding affinity, ligand presentation and thereby cell adhesion could be controlled. As compared to current strategies for the fabrication of dynamic biointerfaces, for example, through reversible covalent or host–guest interactions, such a molecularly tunable dynamic system based on a surface‐imprinting process may unlock new applications in in situ cell biology, diagnostics, and regenerative medicine.
Magnetless Device for Conducting Three‐Dimensional Spin‐Specific Electrochemistry
Authors: Kumar Anup , Capua Eyal , Vankayala Kiran , Fontanesi Claudio , Naaman Ron
Published: September 2017

Electron spin states play an important role in many chemical processes. Most spin‐state studies require the application of a magnetic field. Recently it was found that the transport of electrons through chiral molecules also depends on their spin states and may also play a role in enantiorecognition. Electrochemistry is an important tool for studying spin‐specific processes and enantioseparation of chiral molecules. A new device is presented, which serves as the working electrode in electrochemical cells and is capable of providing information on the correlation of spin selectivity and the electrochemical process. The device is based on the Hall effect and it eliminates the need to apply an external magnetic field. Spin‐selective electron transfer through chiral molecules can be monitored and the relationship between the enantiorecognition process and the spin of electrons elucidated.
Non‐Uniform Optical Inscription of Actuation Domains in a Liquid Crystal Polymer of Uniaxial Orientation: An Approach to Complex and Programmable Shape Changes
Authors: Yang Rong , Zhao Yue
Published: September 2017

Achieving complex shape change of liquid‐crystal polymer networks (LCNs) under stimulation generally requires spatial configuration of the orientation direction, that is, patterned directors, of liquid crystal monomers prior to polymerization by means of treated surfaces. A strategy is demonstrated that needs only the simple uniaxial orientation of mesogens (monodomain) induced by mechanical stretching of LCNs. Using a rationally designed liquid crystal polymer, photocrosslinking is utilized to pattern or spatially organize the actuating monodomains in order to generate a differential contractile and/or extensional force field required for targeted shape change. Moreover, the approach enables versatile actuation modes and allows multiple shape changes to be programmed on a single piece of the polymer. This important feature is demonstrated with a specimen cut to have eight strips that, upon thermal stimulation, simultaneously display eight types of shape morphing.
A Smart Metal–Organic Framework Nanomaterial for Lung Targeting
Authors: Simon‐Yarza Teresa , Giménez‐Marqués Mónica , Mrimi Rhizlaine , Mielcarek Angelika , Gref Ruxandra , Horcajada Patricia , Serre Christian , Couvreur Patrick
Published: September 2017

Despite high morbidity and mortality associated with lung diseases, addressing drugs towards lung tissue remains a pending task. Particle lung filtration has been proposed for passive lung targeting and drug delivery. However, toxicity issues derived from the long‐term presence of the particles must be overcome. By exploiting some of the ignored properties of nanosized metal–organic frameworks it is possible to achieve impressive antitumoral effects on experimental lung tumors, even without the need to engineer the surface of the material. In fact, it was discovered that, based on unique pH‐responsiveness and reversible aggregation behaviors, nanoMOF was capable of targeting lung tissue. At the neutral pH of the blood, the nanoMOFs form aggregates with the adequate size to be retained in lung capillaries. Within 24 h they then disaggregate and release their drug payload. This phenomenon was compatible with lung tissue physiology.
Nickel‐Catalyzed N‐Alkylation of Acylhydrazines and Arylamines Using Alcohols and Enantioselective Examples
Authors: Yang Peng , Zhang Caili , Ma Yu , Zhang Caiyun , Li Aijie , Tang Bo , Zhou Jianrong Steve
Published: September 2017

A borrowing‐hydrogen reaction between amines and alcohols is an atom‐economic way to prepare alkylamines, ideally with water as the sole byproduct. Herein, nickel catalysts are used for direct N‐alkylation of hydrazides and arylamines using racemic alcohols. Moreover, a nickel catalyst of (S)‐binapine was used for an asymmetric N‐alkylation of benzohydrazide with racemic benzylic alcohols.
Glass fiber reinforced and β‐nucleating agents regulated polypropylene: A complementary approach and a case study
Authors: Cui Linfang , Wang Penglei , Zhang Yagang , Zhou Xin , Xu Lu , Zhang Lan , Zhang Letao , Liu Li , Guo Xinfeng
Published: September 2017

A two‐step process for preparing glass fibers (GFs) reinforced β‐nucleated PP composites was designed and developed. The complementary approach combined GFs reinforcement and β‐nucleating agents regulation using N,N′‐dicyclohexyl‐2,6‐napthalene‐dicarboxamide (TMB‐5) in the presence of maleic anhydride grafted polypropylene (PP‐g‐MA) through extrusion blending. The influence of TMB‐5 and GFs on the mechanical properties and crystallization behavior of PP was studied by mechanical test, wide‐angle X‐ray diffraction, differential scanning calorimetry, and scanning electron microscopy. A distinct complementary effect of GFs and β‐nucleating agent TMB‐5 on mechanical properties and crystallization behavior of PP was observed. Results showed that addition of 20 wt % GFs and 0.1 wt % TMB‐5 into PP matrix with the two‐step process could lead to significant increase to its mechanical properties: specifically 64.8% improvement in tensile strength, 107.1% enhancement in flexural modulus, and 167.7% increasement in notched impact strength compared to that of neat PP. Furthermore, with the combination of TMB‐5 and GFs, not only led to promoted interfacial adhesion, but also significantly improved overall comprehensive mechanical properties. The complementary process provided an alternative approach for the development of PP with balanced toughnesss and stiffness. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45768.
Synthesis and Functional Investigations of Computer Designed Novel Cladribine‐Like Compounds for the Treatment of Multiple Sclerosis
Authors: Yavuz Serkan , Çetin Aysu , Akdemir Atilla , Doyduk Doğukan , Dişli Ali , Çelik Turgut Gurbet , Şen Alaattin , Yıldırır Yılmaz
Published: September 2017

Cladribine (2‐CdA) is used as an anti‐cancer drug but is currently studied as a potential treatment for use in relapsing‐remitting multiple sclerosis (MS). In this study, we computer designed, synthesized, and characterized two novel derivatives of 2‐CdA, K1–5d and K2–4c, and investigated their underlying mechanism of beneficial effect using the CCRF‐CEM and RAJI cell lines. For this purpose, we first determined their effect on MS and DNA damage and repair‐related gene expression profiles using custom arrays along with 2‐CdA treatment at non‐toxic doses. Then, we determined whether cells underwent apoptosis after treatment with 2‐CdA, K1–5d, and K2–4c in CCRF‐CEM and RAJI cells, using the DNA fragmentation assay. It was found that both derivatives modulated the expression of the pathway‐related genes that are important in inflammatory signaling, apoptosis, ATM/ATR, double‐strand break repair, and the cell cycle. Furthermore, 2‐CdA, K1–5d, and K2–4c significantly activated apoptosis in both cell lines. In summary, our data demonstrate that although both derivatives act as anti‐inflammatory and apoptotic agents, inducing the accumulation of DNA strand breaks and activating the ultimate tumor suppressor p53 in T and B lymphocytes, the K1–5d derivative has shown more promising activities for further studies.
Side‐Chain‐Directed Dispersion of MoS2 Nanosheets by V‐Shaped Polyaromatic Compounds
Authors: Matsumoto Atsushi , Jono Keisuke , Akita Munetaka , Yoshizawa Michito
Published: September 2017

Bulk molybdenum disulfide (MoS2) itself is virtually insoluble in common organic solvents because of the tight stacks of multiple MoS2 nanosheets. Here we report that V‐shaped polyaromatic compounds with non‐ionic side chains can efficiently exfoliate and disperse the inorganic nanosheets. Simple grinding and sonication (less than total 1 h) of MoS2 powder with the V‐shaped compounds gave rise to large MoS2 nanosheets highly dispersed in NMP through efficient host‐guest S–π interactions. DLS and AFM analyses revealed that the lateral sizes (ca. 150–270 nm) and thicknesses (ca. 2–8 nm) of the products depend on the identity of the non‐ionic side chains on the V‐shaped dispersant.
Transition‐Metal‐Free Reaction of Aryltrimethylammonium Iodides with Arylzinc Reagents
Authors: Dai Wei‐Can , Wang Zhong‐Xia
Published: September 2017

Reaction of aryltrimethylammonium iodides with arylzinc chlorides in the absence of a transition‐metal catalyst to form biaryl compounds was performed under mild conditions. The reaction was suitable for a broad scope of substrates and exhibited good compatibility of functional groups. The Mg2+ ion was demonstrated to markedly promote the reaction.
ℓ2 Gain Estimation and Visualization of A Control Parameter Set in 3D Space Using Plant Response Data
Authors: Saeki Masami
Published: September 2017

In this paper, a novel parameter space approach that uses volume rendering is proposed to visualize controller parameter sets that consist of three controller parameters. An off‐line design method for robust control using plant response data is also studied. A solution set with equal ℓ2 gain can be visualized as isosurfaces in three‐dimensional space, and the designer can visually select an appropriate parameter. This numerical method is applicable to many practical specifications, in contrast to analytical methods based on solving equations. An estimation method based on the extension theorem and a method using bandpass filters are both considered as possible methods for estimating the ℓ2 gain of the sensitivity functions when using grid points on the order of tens of thousands to create the volume data.The former method is superior to the latter with respect to accuracy but impractical with respect to computational load. The latter method is hence practical, because the computing time is reduced to less than 0.05 s for about 300,000 grid points by parallel computation with a graphical processing unit.
Cancer Immunotherapy Using CAR‐T Cells: From the Research Bench to the Assembly Line
Authors: Gomes‐Silva Diogo , Ramos Carlos A.
Published: September 2017

The focus of cancer treatment has recently shifted toward targeted therapies, including immunotherapy, which allow better individualization of care and are hoped to increase the probability of success for patients. Specifically, T cells genetically modified to express chimeric antigen receptors (CARs; CAR‐T cells) have generated exciting results. Recent clinical successes with this cutting‐edge therapy have helped to push CAR‐T cells toward approval for wider use. However, several limitations need to be addressed before the widespread use of CAR‐T cells as a standard treatment. Here, a succinct background on adoptive T‐cell therapy (ATCT)is given. A brief overview of the structure of CARs, how they are introduced into T cells, and how CAR‐T cell expansion and selection is achieved in vitro is then presented. Some of the challenges in CAR design are discussed, as well as the difficulties that arise in large‐scale CAR‐T cell manufacture that will need to be addressed to achieve successful commercialization of this type of cell therapy. Finally, developments already on the horizon are discussed.
Polymeric SpyCatcher Scaffold Enables Bioconjugation in a Ratio‐Controllable Manner
Authors: Jia Lili , Minamihata Kosuke , Ichinose Hirofumi , Tsumoto Kouhei , Kamiya Noriho
Published: September 2017

Conjugating enzymes into a large protein assembly often results in an enhancement of overall catalytic activity, especially when different types of enzymes that work cooperatively are assembled together. However, exploring the proper method to achieve protein assemblies with high stability and also to avoid loss of the function of each component for efficient enzyme clustering is remained challenging. Assembling proteins onto synthetic scaffolds through varied post‐translational modification methods is particularly favored since the proteins can be site‐specifically conjugated together with less activity loss. Here, a SpyCatcher polymer is prepared through catalytic reaction of horseradish peroxidase (HRP) and serves as a polymeric proteinaceous scaffold for construction of protein assemblies. Taking advantage of the favorable SpyCatcher–SpyTag interaction, SpyTagged proteins can be easily assembled onto the polymeric SpyCatcher scaffold with controllable binding ratio and site specificity. Firstly, the feasibility of construction of ratio‐controllable binary artificial hemicellulosomes by assembling endoxylanase and arabinofuranosidase is explored. This construct achieves higher sugar conversion than that of the free enzymes when the proportion of arabinofuranosidase is high, because the close spatial proximity of the enzymes allows them to work in a synergistic manner. Another application for biosensing is developed by conjugating SpyTagged Nanoluc and protein G onto SpyCatcher polymer. Due to the protein clustering effect, an amplified luminescent intensity is achieved by the resulting conjugates than chimera protein of Nanoluc and protein G in ovalbumin detection in ELISA.
Heterologous erythromycin production across strain and plasmid construction
Authors: Fang Lei , Guell Marc , Church George M. , Pfeifer Blaine A.
Published: September 2017

The establishment of erythromycin production within the heterologous host E. coli marked an accomplishment in genetic transfer capacity. Namely, over 20 genes and 50 kb of DNA was introduced to E. coli for successful heterologous biosynthetic reconstitution. However, the prospect for production levels that approach those of the native host requires the application of engineering tools associated with E. coli. In this report, metabolic and genomic engineering were implemented to improve the E. coli cellular background and the plasmid platform supporting heterologous erythromycin formation. Results include improved plasmid stability and metabolic support for biosynthetic product formation. Specifically, the new plasmid design for erythromycin formation allowed for ≥89% stability relative to current standards (20% stability). In addition, the new strain (termed LF01) designed to improve carbon flow to the erythromycin biosynthetic pathway provided a 400% improvement in titer level. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:271–276, 2018
Novel ATP‐competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells
Authors: Yamaji Masayuki , Ota Akinobu , Wahiduzzaman Md , Karnan Sivasundaram , Hyodo Toshinori , Konishi Hiroyuki , Tsuzuki Shinobu , Hosokawa Yoshitaka , Haniuda Masayuki
Published: September 2017

Malignant pleural mesothelioma (MPM), an asbestos‐related occupational disease, is an aggressive and incurable tumor of the thoracic cavity. Despite recent advances in MPM treatment, overall survival of patients with MPM is very low. Recent studies have implicated that PI3K/Akt signaling is involved in MPM cell survival and development. To investigate the effects of Akt inhibitors on MPM cell survival, we examined the effects of nine selective Akt inhibitors, namely, afuresertib, Akti‐1/2, AZD5363, GSK690693, ipatasertib, MK‐2206, perifosine, PHT‐427, and TIC10, on six MPM cell lines, namely, ACC‐MESO‐4, Y‐MESO‐8A, MSTO‐211H, NCI‐H28, NCI‐H290, and NCI‐H2052, and a normal mesothelial cell line MeT‐5A. Comparison of IC50 values of the Akt inhibitors showed that afuresertib, an ATP‐competitive specific Akt inhibitor, exerted tumor‐specific effects on MPM cells. Afuresertib significantly increased caspase‐3 and caspase‐7 activities and apoptotic cell number among ACC‐MESO‐4 and MSTO‐211H cells. Moreover, afuresertib strongly arrested the cell cycle in the G1 phase. Western blotting analysis showed that afuresertib increased the expression of p21WAF1/CIP1 and decreased the phosphorylation of Akt substrates, including GSK‐3β and FOXO family proteins. These results suggest that afuresertib‐induced p21 expression promotes G1 phase arrest by inducing FOXO activity. Furthermore, afuresertib significantly enhanced cisplatin‐induced cytotoxicity. Interestingly, results of gene set enrichment analysis showed that afuresertib modulated the expression E2F1 and MYC, which are associated with fibroblast core serum response. Together, these results suggest that afuresertib is a useful anticancer drug for treating patients with MPM.
Bone marrow biopsy superiority over PET/CT in predicting progression‐free survival in a homogeneously‐treated cohort of diffuse large B‐cell lymphoma
Authors: Chen‐Liang Tzu‐Hua , Martín‐Santos Taida , Jerez Andrés , Rodríguez‐García Guillermo , Senent Leonor , Martínez‐Millán Cristina , Muiña Begoña , Orero Mayte , Teruel Anabel , Martín Alejandro , Gómez‐Espuch Joaquín , Kennedy Kyra , Benet Carmen , Raya José María , Fernández‐González Marta , de la Cruz Fátima , Guinot Marta , Villegas Carolina , Ballester Isabel , Baile Mónica , Moya María , López‐Jiménez Javier , Frutos Laura , Navarro José Luis , Uña Jon , Fernández‐López Rosa , Igua Carolina , Contreras José , Sánchez‐Vañó Raquel , Cozar María del Puig , Tamayo Pilar , Mucientes Jorge , Sánchez‐Blanco José Javier , Pérez‐Ceballos Elena , Ortuño Francisco José
Published: September 2017

Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy (BMB) and PET/CT as part of the staging of diffuse large B‐cell lymphoma (DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R‐CHOP/21 as first line (n = 203) were included in the survival analysis. With a median follow‐up of 25 months the estimated 3‐year progression‐free survival (PFS) and overall survival (OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB‐BMI [bone marrow involvement](+) (HR: 3.6) and ECOG PS > 1 (HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old (HR: 2.4), ECOG PS >1 (HR: 2.4), and abnormally elevated B2‐microglobulin levels (HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first‐line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/CT could not independently predict a shorter PFS and/or OS.
Visible‐Light‐Assisted Cobalt‐2‐(hydroxyimino)‐1‐phenylpropan‐1‐one Complex Catalyzed Pd/Cu‐Free Sonogashira–Hagihara Cross‐Coupling Reaction
Authors: Song Jin‐Yi , Zhou Xuan , Song He , Liu Yang , Zhao Hong‐Yan , Sun Zhi‐Zhong , Chu Wen‐Yi
Published: September 2017

An effective and inexpensive strategy for the Co(C9H9NO2)3 catalyzed Sonogashira–Hagihara cross‐coupling reaction of aryl bromides containing electron‐rich and electron‐poor substituents with terminal alkynes was demonstrated. The reaction proceeded smoothly in the presence of ethylene glycol as additive and K2CO3 as base in DMF under visible light illumination, and 23 alkyne products were afforded in moderate to excellent yields, including four new diaryl ethynes. Compared with the high‐cost palladium catalyst, cobalt is an inexpensive catalyst with a preponderance of technologized production, and the palladium/copper‐free catalytic system not only provided an efficient process with mild reaction conditions, but also enhanced the substrate group tolerance.
Effect of 1‐Methylimidazole on CO2 Absorption by Diethylenetriamine Aqueous Solutions
Authors: You Jong Kyun , Lee Hwa Young , Hong Yeon Ki
Published: September 2017

Phase‐splitting absorbents represent a promising technology in relation to the low energy levels required during the CO2 capture process. 1‐Methylimidazole was added to a diethylenetriamine (DETA) aqueous solution for high CO2 loading via phase splitting of absorbents during CO2 absorption. Phase splitting was observed during the absorption process when the CO2 loading reached a value suitable for the mixture of DETA, 1‐methylimidazole, and water. The distribution of individual components in each phase was determined according to the total organic carbon and gas chromatography. DETA and CO2 were concentrated in the bottom phase, 1‐methylimidazole mostly in the top phase. Phase splitting during CO2 absorption was mainly due to the solubility limitation of DETA carbamate into 1‐methylimidazole.
Nitrogen‐Doped Hierarchical Porous Carbon Framework Derived from Waste Pig Nails for High‐Performance Supercapacitors
Authors: Zhou Yibei , Ren Juan , Xia Li , Wu Huali , Xie Fengyu , Zheng Qiaoji , Xu Chenggang , Lin Dunmin
Published: September 2017

In situ nitrogen‐doped hierarchical porous carbon was synthesized by using waste protein‐rich pig nails as precursors in a facile KOH activation method. The microstructure and electrochemical characteristics of the materials were investigated by tuning the amount of KOH. When the weight ratio of KOH to pig nails is 1 : 1, the obtained nitrogen‐doped hierarchical porous carbon (NHPC‐1) exhibits the largest specific surface area (2569 m2 g−1) with interconnected porous network structure, which are beneficial to ion/electron storage and transfer. In addition, abundant nitrogen of 2.8 at % in the NHPC‐1 also contributes to the high electrochemical activity of the supercapacitor during the charging/discharging process. As a result, the NHPC‐1 electrode in the supercapacitor exhibits a high specific capacitance of 231 F g−1 at 1 A g−1 and superior retention of 98 % after 5000 cycles at 1 A g−1 in 6 M KOH electrolyte. Additionally, the assembled symmetric device based on NHPC‐1 exhibits a high energy density of 7 Wh kg−1 at a power density of 500 W kg−1. Our study suggests that waste pig nails can act as low‐cost and renewable carbon precursors for high performance supercapacitor.
Effect of the ortho‐Hydroxyl Groups on a Bipyridine Ligand of Iridium Complexes for the High‐Pressure Gas Generation from the Catalytic Decomposition of Formic Acid
Authors: Iguchi Masayuki , Zhong Heng , Himeda Yuichiro , Kawanami Hajime
Published: September 2017

The hydroxyl groups of a 2,2′‐bipyridine (bpy) ligand near the metal center activated the catalytic performance of the Ir complex for the dehydrogenation of formic acid at high pressure. The position of the hydroxyl groups on the ligand affected the catalytic durability for the high‐pressure H2 generation through the decomposition of formic acid. The Ir complex with a bipyridine ligand functionalized with para‐hydroxyl groups shows a good durability with a constant catalytic activity during the reaction even under high‐pressure conditions, whereas deactivation was observed for an Ir complex with a bipyridine ligand with ortho‐hydroxyl groups (2). In the presence of high‐pressure H2, complex 2 decomposed into the ligand and an Ir trihydride complex through the isomerization of the bpy ligand. This work provides the development of a durable catalyst for the high‐pressure H2 production from formic acid.
Near‐Infrared‐Absorbing Organometallic Diruthenium Complex Intermediates: Evidence for Bridging Anthrasemiquinone Formation and against Mixed Valency
Authors: Kamatchi Thangavel Sathiya , Mondal Sudipta , Scherer Thomas , Bubrin Martina , Natarajan Karuppannan , Kaim Wolfgang
Published: September 2017

The new redox‐active complexes [RuH(CO)(EPh3)2(μ‐Q2−)RuH(CO)(EPh3)2], E=P (1) and E=As (2) with the bis‐chelate bridging ligand Q2−=1,4‐dioxido‐9,10‐anthraquinone were prepared and characterised. The related compound [RuCl(CO)(PPh3)2(μ‐Qx2−)RuCl(CO)(PPh3)2] (4) with E=P and Qx2−=5,8‐dioxido‐1,4‐naphthoquinone 4 revealed trans‐positioned PPh3 groups. The electrogenerated one‐electron oxidised states 1+ and 2+ were examined using spectroelectrochemical techniques (EPR, IR and UV/Vis/NIR). In situ EPR studies gave spectra with 31P or 75As hyperfine splitting of about 16 Gauss, small 99, 101Ru coupling and small g‐anisotropy in the frozen solution state. The 31P and 75As hyperfine values reflect axial positioning of the four Ru−E bonds relative to the plane of an anthrasemiquinone bridge. Single CO stretching bands around 1910 cm−1 of the precursors 1 and 2 shift by about 25 cm−1 to higher energies on oxidation. The direction, uniformity and the extent of the shifts confirm ligand bridge‐based oxidation. Absorbance by the cations in the near infrared region is thus assigned to intra‐ligand transitions of ruthenium(II)‐bonded anthrasemiquinones and not to intervalence charge transfer of mixed‐valent species. Ruthenium(II) stabilisation by CO and EPh3 is made responsible for the anthrasemiquinone formation instead of metal‐centered oxidation.
Catalytic Asymmetric Direct Vinylogous Aldol Reaction of Isatins with β,γ‐Unsaturated Butenolides
Authors: Tang Qiong , Lin Lili , Ji Jie , Hu Haipeng , Liu Xiaohua , Feng Xiaoming
Published: September 2017

A direct asymmetric vinylogous aldol reaction of nonactivated natural α‐angelica lactone to isatins has been developed. With a N,N′‐dioxide‐Sc(OTf)3 complex as catalyst, a variety of δ‐hydroxy butenolides bearing congested adjacent tetrasubstituted stereocenters were obtained in good yields with high diastereoselectivities and excellent enantioselectivities. Besides, a possible transition state was proposed to explain the origin of the asymmetric induction.
Integrative Self‐Sorting of Bipyridinium/Diazapyrenium‐Based Ligands into Pseudo[1]rotaxanes
Authors: Rama Tamara , Blanco‐Gómez Arturo , Neira Iago , Domarco Olaya , García Marcos D. , Quintela José M. , Peinador Carlos
Published: September 2017

We present here the design and synthesis of a series of multicomponent supramolecular architectures, structures formed by the PdII/PtII‐directed integrative social self‐sorting in aqueous media of pairs of complementary N‐monoalkyl‐4,4′‐bipyridinium/2,7‐diazapyrenium‐based ligands. Out of the different potential outcomes of the processes, we have found out how the designed systems selectively enhance the production of pseudo[1]rotaxanes, hermaphroditic host–guest aggregates that maximize the strength of the occurring π–π, C−H⋅⋅⋅π, and hydrophobic interactions, as well as the number of those interactions per receptor. It is also demonstrated how both integrative social and narcissistic PdII‐directed self‐sorting can occur orthogonally and concomitantly for this type of ditopic ligands.
Mimicking Intermolecular Interactions of Tight Protein–Protein Complexes for Small‐Molecule Antagonists
Authors: Xu David , Bum‐Erdene Khuchtumur , Si Yubing , Zhou Donghui , Ghozayel Mona K. , Meroueh Samy O.
Published: September 2017

Tight protein–protein interactions (Kd<100 nm) that occur over a large binding interface (>1000 Å2) are highly challenging to disrupt with small molecules. Historically, the design of small molecules to inhibit protein–protein interactions has focused on mimicking the position of interface protein ligand side chains. Here, we explore mimicry of the pairwise intermolecular interactions of the native protein ligand with residues of the protein receptor to enrich commercial libraries for small‐molecule inhibitors of tight protein–protein interactions. We use the high‐affinity interaction (Kd=1 nm) between the urokinase receptor (uPAR) and its ligand urokinase (uPA) to test our methods. We introduce three methods for rank‐ordering small molecules docked to uPAR: 1) a new fingerprint approach that represents uPA′s pairwise interaction energies with uPAR residues; 2) a pharmacophore approach to identify small molecules that mimic the position of uPA interface residues; and 3) a combined fingerprint and pharmacophore approach. Our work led to small molecules with novel chemotypes that inhibited a tight uPAR⋅uPA protein–protein interaction with single‐digit micromolar IC50 values. We also report the extensive work that identified several of the hits as either lacking stability, thiol reactive, or redox active. This work suggests that mimicking the binding profile of the native ligand and the position of interface residues can be an effective strategy to enrich commercial libraries for small‐molecule inhibitors of tight protein–protein interactions.
Comparison of the toxicity profile of PD‐1 versus PD‐L1 inhibitors in non–small cell lung cancer: A systematic analysis of the literature
Authors: Pillai Rathi N. , Behera Madhusmita , Owonikoko Taofeek K. , Kamphorst Alice O. , Pakkala Suchita , Belani Chandra P. , Khuri Fadlo R. , Ahmed Rafi , Ramalingam Suresh S.
Published: September 2017

BACKGROUND

Monoclonal antibodies against programmed cell death protein 1 (PD‐1) and programmed death ligand 1 (PD‐L1) are effective therapies in patients with non‐small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD‐1 and PD‐L1 inhibitors.

METHODS

An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD‐1 inhibitors (nivolumab and pembrolizumab) and PD‐L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC. A formal systematic analysis was conducted with Comprehensive Meta‐Analysis software (version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between both groups.

RESULTS

A total of 23 studies reported between 2013 and 2016 were eligible for analysis. The total number of patients evaluated for toxicities was 3284 patients in the PD‐1 group and 2460 patients in the PD‐L1 group. The baseline patient characteristics of the 2 groups were similar, although there was a trend toward increased squamous histology in the group treated with PD‐L1 (32% vs 25%; P = .6). There was no difference in response rate noted between PD‐1 (19%) and PD‐L1 (18.6%) inhibitors (P = .17). The incidence of overall adverse events (AEs) was comparable between the PD‐1 and PD‐L1 inhibitors (64% [95% confidence interval (95% CI), 63%‐66%] vs 66% [95% CI, 65%‐69%]; P = .8). Fatigue was the most frequently reported AE with both classes of drugs. Patients treated with PD‐1 inhibitors were found to have a slightly increased rate of immune‐related AEs (16% [95% CI, 14%‐17%] vs 11% [95% CI, 10%‐13%]; P = .07) and pneumonitis (4% [95% CI, 3%‐5%] vs 2% [95% CI, 1%‐3%]; P = .01) compared with patients who received PD‐L1 inhibitors.

CONCLUSIONS

In this systematic review involving 5744 patients with NSCLC, the toxicity and efficacy profiles of PD‐1 and PD‐L1 inhibitors appear to be similar. Cancer 2018;124:271‐7. © 2017 American Cancer Society.
Phase 1, Randomized, Double‐Blind, Placebo‐Controlled Studies on the Safety, Tolerability, and Pharmacokinetics of Naldemedine in Healthy Volunteers
Authors: Fukumura Kazuya , Yokota Takaaki , Baba Yuko , Arjona Ferreira Juan Camilo
Published: September 2017

Naldemedine (S‐297995) is a peripherally acting μ‐opioid receptor antagonist for the treatment of opioid‐induced constipation, a common side effect of opioid therapy. We determined the safety, tolerability, and pharmacokinetic profiles of oral naldemedine in healthy volunteers in 2 randomized, double‐blind, placebo‐controlled, phase 1 studies. In the single ascending dose study, subjects received a single dose of naldemedine (0.1‐100 mg; n = 42) or placebo (n = 14). In the multiple ascending dose study, subjects received once‐daily naldemedine (3‐30 mg; n = 27) or placebo (n = 9) for 10 days. On day 1 of the single ascending dose studies and day 10 of the multiple ascending dose studies, respectively, the maximum plasma concentration levels of naldemedine were 1.98 to 2510 ng/mL and 73.8 to 700 ng/mL, peaked at 0.5 hours and 0.5 to 0.75 hours, and the fraction excreted in urine was 15.9% to 20.5% and 19.7% to 19.1%. There were no major safety or tolerability concerns even at naldemedine doses 150 to 500 times the therapeutic dose of 0.2 mg. The incidence of adverse events was not dose dependent. Gastrointestinal adverse events occurred more frequently with naldemedine vs placebo, and all of these were considered treatment related. Overall, naldemedine was rapidly absorbed, and no safety or tolerability issues were noted at the doses evaluated.
Flow‐Pattern Characterization of Biphasic Electrochemical Cells by Magnetic Resonance Imaging under Forced Hydrodynamic Conditions
Authors: Serial María R. , Velasco Manuel I. , Silletta Emilia V. , Zanotto Franco M. , Dassie Sergio A. , Acosta Rodolfo H.
Published: September 2017

The fluid dynamics of a liquid|liquid system inside a four‐electrode electrochemical cell were studied by velocimetry magnetic resonance imaging (MRI) and flow propagator measurements. To characterize this system fully, three different cell configurations operating at two rotational frequencies were analyzed. Quantitative information about the stability of the liquid|liquid interface and the dynamics of the organic phase were determined. The NMR spectroscopy results were in agreement with the electrochemical measurements performed by using the same experimental setup.
N‐Heterocyclic Carbene Self‐assembled Monolayers on Copper and Gold: Dramatic Effect of Wingtip Groups on Binding, Orientation and Assembly
Authors: Larrea Christian R. , Baddeley Christopher J. , Narouz Mina R. , Mosey Nicholas J. , Horton J. Hugh , Crudden Cathleen M.
Published: September 2017

Self‐assembled monolayers of N‐heterocyclic carbenes (NHCs) on copper are reported. The monolayer structure is highly dependent on the N,N‐substituents on the NHC. On both Cu(111) and Au(111), bulky isopropyl substituents force the NHC to bind perpendicular to the metal surface while methyl‐ or ethyl‐substituted NHCs lie flat. Temperature‐programmed desorption studies show that the NHC binds to Cu(111) with a desorption energy of Edes=152±10 kJ mol−1. NHCs that bind upright desorb cleanly, while flat‐lying NHCs decompose leaving adsorbed organic residues. Scanning tunneling microscopy of methylated NHCs reveals arrays of covalently linked dimers which transform into adsorbed (NHC)2Cu species by extraction of a copper atom from the surface after annealing.
Effectiveness of CSR Advertising: The Role of Reputation, Consumer Attributions, and Emotions
Authors: del Mar García‐De los Salmones María , Perez Andrea
Published: September 2017

Despite companies' wishes to publicise their corporate social responsibility (CSR) activities, communication remains a challenge. This research study tries to contribute to the literature, analysing the antecedents and consequences of attitude towards a CSR advertisement in the financial sector. Specifically, we designed a causal model, which included the prior ethical reputation, the range of possible attributions, and the mix of emotions provoked by the advertisement. We surveyed 225 adults in Spain who evaluated a fictitious advertisement for companies of different ethical reputations, conveying a philanthropic cause. As a result, it was observed that the advertisement generated a mix of intrinsic and extrinsic attributions and a mix of positive and negative emotions, and the prior ethical reputation of the company was a key antecedent of the effectiveness of the communication. Furthermore, a good attitude towards the advertisement has rewards, in terms of improvement of attitudes towards the brand and behavioural intentions. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Corporate Social Responsibility as Stakeholder Engagement: Firm–NGO Collaboration in Sweden
Authors: Fontana Enrico
Published: September 2017

This paper investigates the process of stakeholder collaboration between firms and non‐governmental organizations (NGOs) in Sweden. Collaboration is increasing in importance for corporate social responsibility (CSR); however, the literature does not adequately address how firms and NGOs begin and advance their relationships. This paper focuses on one fashion retailer and four NGOs in Sweden, implementing a resource‐based view to better understand CSR. These NGOs support the firm's CSR toward asylum applicants and low‐income individuals. This study makes three contributions to the CSR literature. First, it finds that the firm and NGOs select each other based on their resources, but for different reasons. Second, it demonstrates that NGOs adjust to corporate demands, but whether this hampers mission integrity depends on the balance between current and future potential for resource acquisition. Finally, it shows the influence of the Swedish context on CSR, arguing that public opinion can be shifted through policy making. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Exploring the Reaction Pathways of Bioglycerol Hydrodeoxygenation to Propene over Molybdena‐Based Catalysts
Authors: Zacharopoulou Vasiliki , Vasiliadou Efterpi S. , Lemonidou Angeliki A.
Published: September 2017

The one‐step reaction of glycerol with hydrogen to form propene selectively is a particularly challenging catalytic pathway that has not yet been explored thoroughly. Molybdena‐based catalysts are active and selective to C−O bond scission; propene is the only product in the gas phase under the standard reaction conditions, and further hydrogenation to propane is impeded. Within this context, this work focuses on the exploration of the reaction pathways and the investigation of various parameters that affect the catalytic performance, such as the role of hydrogen on the product distribution and the effect of the catalyst pretreatment step. Under a hydrogen atmosphere, propene is produced primarily via 2‐propenol, whereas under an inert atmosphere propanal and glycerol dissociation products are formed mainly. The reaction most likely proceeds through a reverse Mars–van Krevelen mechanism as partially reduced Mo species drive the reaction to the formation of the desired product.