bluuebunny/crossref_metadata_2025 huggingface dataset:
CSF1R‐ and SHP2‐Inhibitor‐Loaded Nanoparticles Enhance Cytotoxic Activity and Phagocytosis in Tumor‐Associated Macrophages
Authors: Ramesh Anujan , Kumar Sahana , Nandi Dipika , Kulkarni Ashish
Published: October 2019

Immune modulation of macrophages has emerged as an attractive approach for anti‐cancer therapy. However, there are two main challenges in successfully utilizing macrophages for immunotherapy. First, macrophage colony stimulating factor (MCSF) secreted by cancer cells binds to colony stimulating factor 1 receptor (CSF1‐R) on macrophages and in turn activates the downstream signaling pathway responsible for polarization of tumor‐associated macrophages (TAMs) to immunosuppressive M2 phenotype. Second, ligation of signal regulatory protein α (SIRPα) expressed on myeloid cells to CD47, a transmembrane protein overexpressed on cancer cells, activates the Src homology region 2 (SH2) domain ‐phosphatases SHP‐1 and SHP‐2 in macrophages. This results in activation of “eat‐me‐not” signaling pathway and inhibition of phagocytosis. Here, it is reported that self‐assembled dual‐inhibitor‐loaded nanoparticles (DNTs) target M2 macrophages and simultaneously inhibit CSF1R and SHP2 pathways. This results in efficient repolarization of M2 macrophages to an active M1 phenotype, and superior phagocytic capabilities as compared to individual drug treatments. Furthermore, suboptimal dose administration of DNTs in highly aggressive breast cancer and melanoma mouse models show enhanced anti‐tumor efficacy without any toxicity. These studies demonstrate that the concurrent inhibition of CSF1‐R and SHP2 signaling pathways for macrophage activation and phagocytosis enhancement could be an effective strategy for macrophage‐based immunotherapy.
Interface‐Sliding‐Induced Graphene Quantum Dots Transferring to Fullerene‐Like Quantum Dots and Their Extraordinary Tribological Behavior
Authors: Zhang Renhui , Xiong Liping , Pu Jibin , Lu Zhibin , Zhang Guangan , He Zhongyi
Published: October 2019

Carbon materials such as diamond, fullerene, graphene, and carbon nanotubes possess superior chemical and physical properties, which are widely used in various applications. Especially, since fullerene‐like carbon is successfully converted to graphene during sliding, the sliding‐induced microstructure transfer between carbon‐based materials should be given more attention. Here, the tribological behaviors of graphene‐based materials is investigated under the load of 196 N and the rotational speed of 1450 rpm using a four‐ball wear machine under deionized water. Results show that the friction coefficient continuously decreases with increasing sliding time and the wear scar diameter is just about 0.224 mm. Remarkably, graphene is severely ripped and loses its lubrication performance during sliding. Sliding induces graphene quantum dots converting to fullerene quantum dots, which would cooperate with the sliding‐reduced fullerene‐like structures containing WO2 nanocrystals and sulfurized isobutene as extreme pressure lubricant additives instead of graphene to achieve low friction and wear. This work confirms that the low friction and wear under high load and fast rotation have a close relation to the microstructure transfer of interfacial carbon‐based materials, rather graphene, and provide practical approach for investigating the tribological behaviors of carbon‐based materials.
Coinage Metal Complexes of Chiral N‐Heterocyclic Carbene Ligands: Syntheses and Applications in Asymmetric Catalysis
Authors: Budagumpi Srinivasa , Keri Rangappa S. , Achar Gautam , Brinda K. N.
Published: October 2019

Chiral N‐heterocyclic carbenes (NHCs) have become ligands of choice due to their remarkable catalytic activity in organic transformation reactions. Combining the chiral NHC ligand family and coinage metals became a productive area of research. The organometallic chemistry of coinage metals with the chiral N‐heterocyclic carbene (NHC) ligands is reviewed, with a special emphasis on the synthesis, characterization and possible applications obtained. Significant sections are devoted to the various recently developed coinage metal‐chiral NHC complexes and a detailed comparison of their activities which aims to rationalize the structure–activity relationships. Various methods of preparations of coinage metal‐chiral NHC complexes along with some typical examples of reactivity and mechanisms are covered. Cu‐chiral NHC complexes involved in conjugated additions, allylic substitutions, boration of alkenes, hydrosilylation of ketones and formation of alkenes are covered, along with some remarkable examples and reactivity of Ag‐chiral NHC complexes. Finally, applications of Au‐chiral NHC complexes in the asymmetric cyclization of ester‐functionalized 1,6‐enynes, 1,6‐enyneamines and substituted propargyloxymethanes are also reviewed.

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Transition‐Metal‐Free Synthesis of 1,2‐diphenyl‐1H‐benzo[d] Imidazole Derivatives from N‐phenylbenzimidamides and Cyclohexanones
Authors: Lu Guoqiang , Luo Nan , Hu Fangpeng , Ban Zihui , Zhan Zhenzhen , Huang Guo‐Sheng
Published: October 2019

A transition‐metal‐free strategy for the formation of 1,2‐diphenyl‐1H‐benzo[d] imidazoles from N‐phenylbenzimidamides and cyclohexanones is introduced. This is the first report on the direct synthesis of 1,2‐diphenyl‐1H‐benzo[d] imidazoles from cyclohexanones and N‐phenylbenzimidamides via iodine‐ promoted oxidative cyclization. Non‐aromatic cyclohexanones were smoothly dehydrogenated, and acted as an aryl source using oxygen as a green oxidant. The catalytic use of iodine makes this method quite simple, more economical and convenient. Under optimized conditions, various substituted 1,2‐diphenyl‐1H‐benzo[d] imidazoles were smoothly reacted, and the desired substituted imidazoles were generated with moderate to excellent yields.

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Isomerization‐Asymmetric Hydrogenation Sequence Converting Racemic β‐Ylidenecycloalkanols into Stereocontrolled β‐Substituted Cycloalkanols Using a Ru Catalytic System with Dual Roles
Authors: Arai Noriyoshi , Okabe Yuki , Ohkuma Takeshi
Published: October 2019

Racemic β‐ylidenecycloalkanols were transformed into thecis‐β‐substituted cycloalkanols with high enantio‐ and diastereoselectivities through an isomerization‐asymmetric hydrogenation sequence with the (4,4′‐bi‐1,3‐benzodioxole)‐5,5′‐diylbis[di(3,5‐xylyl)phosphine (DM‐Segphos)/2‐dimethylamino‐1‐phenylethylamine (DMAPEN)‐ruthenium(II) catalyst; such transformation hardly proceeded by single‐step asymmetric hydrogenation. The reaction was usually carried out with a substrate‐to‐catalyst molar ratio of 500 under 4 to 10 atm of H2to afford the products incis/transratio up to 99:1 and 98% ee. Mechanistic experiments suggested that this catalytic system reversibly formed two reactive species, types (I) and (II), through a ruthenacyclic amide intermediate. The amide complex and allylic alcohol reacted to afford the allylic alkoxide complex with partial or full removal of diamine (type (I)), and this type (I) complex catalyzed isomerization of the allylic alcohols into the racemic α‐substituted ketones. The RuH2complex with chelation of diamine (type (II)) formed by reaction of the amide complex and hydrogen promoted asymmetric hydrogenation of racemic α‐substituted ketone into the stereocontrolled β‐substituted cycloalkanols through dynamic kinetic resolution.

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A Simple Structure Conjugated Polymer for High Mobility Organic Thin Film Transistors Processed from Nonchlorinated Solvent
Authors: Wang Zhongli , Song Xianneng , Jiang Yu , Zhang Jidong , Yu Xi , Deng Yunfeng , Han Yang , Hu Wenping , Geng Yanhou
Published: October 2019

Herein, a simple structure, nonchlorinated solvent processable high mobility donor–acceptor conjugated polymer, poly(2,5‐bis(4‐hexyldodecyl)‐2,5‐dihydro‐3,6‐di‐2‐thienyl‐pyrrolo[3,4‐c]pyrrole‐1,4‐dione‐alt‐thiophene) (PDPPT3‐HDO), is reported. The enhanced solubility in nonchlorinated solvent is realized based on a denser alkyl side chains strategy by incorporating small size comonomer thiophene. An associated benefit of thiophene comonomer is the remarkable structural simplicity of the resulting polymer, which is advantageous for industrial scaling up. The alkyl side chain density and structure of PDPPT3‐HDO can efficiently control the self‐assembly properties in solution and film. By bar coating from o‐xylene solution, PDPPT3‐HDO forms aligned films and exhibits high hole mobility of up to 9.24 cm2 V−1 s−1 in organic thin film transistors (OTFTs). Notably, the bar‐coated OTFT based on PDPPT3‐HDO shows a close to ideal transistor model and a high mobility reliability factor of 87%. The multiple benefits of increased side chain density strategy may encourage the design of high mobility polymers that meet the requirements of mass production of OTFT materials and devices.
An Aqueous Zn‐Ion Hybrid Supercapacitor with High Energy Density and Ultrastability up to 80 000 Cycles
Authors: Wu Shuilin , Chen Yatu , Jiao Tianpeng , Zhou Jun , Cheng Junye , Liu Bin , Yang Shaoran , Zhang Kaili , Zhang Wenjun
Published: October 2019

Integrating a battery‐type electrode to build a hybrid supercapacitor is a promising approach to improve the overall energy density of a supercapacitor‐type energy storage device without sacrificing its power output. However, this strategy is usually achieved at the expense of cycling lifespan. In this work, a hybrid supercapacitor comprising Zn foil and porous carbon derived from chemical activated graphene (aMEGO) is developed, and the trade‐off between energy density and cycling life is well‐balanced by the utilization of 3 m Zn(CF3SO3)2 electrolyte with high Zn stripping/plating efficiency. Such a hybrid supercapacitor demonstrates an energy density of 106.3 Wh kg−1 and a power density of 31.4 kW kg−1, and significantly a wide operation voltage of 1.9 V is achieved in aqueous electrolyte. Benefitting from the high Zn stripping/plating efficiency, the Zn‐aMEGO hybrid‐supercapacitor also exhibits an ultralong cycling life up to 80 000 cycles with capacity retention of 93%, which is comparable to that of conventional electrochemical double‐layer capacitors.
Emergency Medicine Education Research Since the 2012 Consensus Conference: How Far Have We Come and What’s Next?
Authors: Gottlieb Michael , Chan Teresa M. , Clarke Samuel O. , Ilgen Jonathan S. , Jordan Jaime , Moschella Phillip , Santen Sally A. , Yarris Lalena M. , Coates Wendy C.
Published: October 2019

In 2012, the Society for Academic Emergency Medicine convened a consensus conference on the state of medical education research with goals of defining and advancing a future research agenda. Since that time, emergency medicine (EM) education research has grown significantly. A task force of EM education experts was assembled and sought to understand the current state of EM education research and future directions. Among the advances are increases in medical education fellowships, advanced degree and certification programs, faculty development programs, publication venues, and funding. These findings are discussed in light of the prior objectives from the 2012 consensus conference, and recommendations for future directions are provided.
Cell‐of‐origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B‐cell lymphoma
Authors: Abdulla Maysaa , Hollander Peter , Pandzic Tatjana , Mansouri Larry , Ednersson Susanne Bram , Andersson Per‐Ola , Hultdin Magnus , Fors Maja , Erlanson Martin , Degerman Sofie , Petersen Helga Munch , Asmar Fazila , Grønbæk Kirsten , Enblad Gunilla , Cavelier Lucia , Rosenquist Richard , Amini Rose‐Marie
Published: October 2019

The tumor cells in diffuse large B‐cell lymphomas (DLBCL) are considered to originate from germinal center derived B‐cells (GCB) or activated B‐cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC‐based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non‐GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression‐free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression‐free survival differed significantly. Importantly, patients assigned as non‐GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.
Duplication 2p16 is associated with perisylvian polymicrogyria
Authors: Amrom Dina , Poduri Annapurna , Goldman Jennifer S. , Dan Bernard , Deconinck Nicolas , Pichon Bruno , Nadaf Javad , Andermann Frederick , Andermann Eva , Walsh Christopher A. , Dobyns William B.
Published: October 2019

Polymicrogyria (PMG) is a heterogeneous brain malformation that may result from prenatal vascular disruption or infection, or from numerous genetic causes that still remain difficult to identify. We identified three unrelated patients with polymicrogyria and duplications of chromosome 2p, defined the smallest region of overlap, and performed gene pathway analysis using Cytoscape. The smallest region of overlap in all three children involved 2p16.1‐p16.3. All three children have bilateral perisylvian polymicrogyria (BPP), intrauterine and postnatal growth deficiency, similar dysmorphic features, and poor feeding. Two of the three children had documented intellectual disability. Gene pathway analysis suggested a number of developmentally relevant genes and gene clusters that were over‐represented in the critical region. We narrowed a rare locus for polymicrogyria to a region of 2p16.1‐p16.3 that contains 33–34 genes, 23 of which are expressed in cerebral cortex during human fetal development. Using pathway analysis, we showed that several of the duplicated genes contribute to neurodevelopmental pathways including morphogen, cytokine, hormonal and growth factor signaling, regulation of cell cycle progression, cell morphogenesis, axonal guidance, and neuronal migration. These findings strengthen the evidence for a novel locus associated with polymicrogyria on 2p16.1‐p16.3, and comprise the first step in defining the underlying genetic etiology.
A Realistic Evaluation of Danish Perioperative Nurses’ Documentation Practices
Authors: Søndergaard Susanne Friis , Frederiksen Kirsten , Sørensen Erik Elgaard , Lorentzen Vibeke
Published: October 2019

Nursing care documentation is an important aspect of clinical decision‐making processes and affects patient safety. Documentation in the perioperative setting has been described as poor and incomplete and varies among nurses. The purpose of this qualitative study was to examine perioperative nurses’ documentation practices using a realistic evaluation framework that focuses on relationships between context, mechanisms, and outcomes. Through participant observations using multiple qualitative data‐generation methods, the study found that perioperative nurses’ documentation practices are driven by a mix of educational, cultural, and organizational factors, including competing demands, local values and traditions, and everyday circumstances. Understanding the cultures of different subgroups in the perioperative setting may help improve nurses’ documentation practices.
Removal of acid dyes from aqueous solutions using a new eco‐friendly nanocomposite of CoFe2O4 modified with Tragacanth gum
Authors: Moghaddam Ali Zeraatkar , Jazi Mehdi Erfani , Allahrasani Ali , Ganjali Mohammad Reza , Badiei Alireza
Published: October 2019

A new composite of cobalt ferrite and Tragacanth gum (TG) was developed and applied to remove methyl orange (MO) and methyl red (MR) from wastewater samples simultaneously. The results showed that the presence of TG improved the capability of cobalt ferrite in removing the pollutants in considerably. The adsorption properties and surface morphology of the sorbent were compared with those of bare cobalt ferrite, TG, and TG grafted copolymer. The properties of the adsorbents were studied using Fourier transform infrared, scanning electron microscope, transmission electron microscope, X‐ray diffraction, and vibrating sample magnetometer, and the effects of different factors such as the amount of the adsorbent, sample pH, contact time, and initial concentration were also evaluated and optimized through response surface methodology using central composite design. The optimal conditions for the adsorption of both dyes (100 mg L−1 as the concentration) were pH of 4.0, adsorbent dose of 0.5 mg mL−1, and contact time of 110 min. Under these conditions, the MO and MR adsorption processes were found to follow pseudo‐second‐order kinetic model. The equilibrium adsorption data followed the Langmuir isotherm and the highest adsorption capacity was determined to be 336 and 387 mg g−1 for MO and MR, respectively. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48605.
Enhanced mechanical properties of poly(lactic acid) composites with ultrathin nanosheets of MXene modified by stearic acid
Authors: Yi Zhuwu , Yang Jian , Liu Xiaochao , Mao Long , Cui Lingna , Liu Yuejun
Published: October 2019

MXene modified by stearic acid (Ti3C2Tx‐g‐SA) is incorporated into poly(lactic acid) (PLA) matrix to prepare Ti3C2Tx‐g‐SA/PLA composites. The effects of Ti3C2Tx‐g‐SA to pure PLA are investigated, including crystallization, mechanical, and thermal properties. Fourier transform infrared spectroscopy and X‐ray diffraction analyses confirm that Ti3C2Tx interlayer is successfully intercalated by SA, and the interlayer spacing of Ti3C2Tx is increased. Differential scanning calorimetry illustrates that the cold crystallization enthalpy (ΔHcc), melting enthalpy (ΔHm), and crystallinity (Xc) of Ti3C2Tx‐g‐SA/PLA composites are improved by the plasticization and heterogeneous nucleation effect of Ti3C2Tx‐g‐SA. Specially, the Ti3C2Tx‐g‐SA/PLA composites exhibit excellent mechanical properties at an appropriate content of the Ti3C2Tx‐g‐SA. Compared with pure PLA, the elongation at break of the Ti3C2Tx‐g‐SA/PLA composite is increased 5.9‐fold (up to 131.6%) when only containing 0.5 wt % Ti3C2Tx‐g‐SA. Besides, the Ti3C2Tx‐g‐SA/PLA composites exhibit good thermal stability in the low loading (lower than 1 wt %) of Ti3C2Tx‐g‐SA. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48621.
A review of data science in business and industry and a future view
Authors: Vicario Grazia , Coleman Shirley
Published: October 2019

The aim of this paper is to frame Data Science, a fashion and emerging topic nowadays in the context of business and industry. We open with a discussion about the origin of Data Science and its requirement for a challenging mix of capability in data analytics, information technology, and business know‐how. The mission of Data Science is to provide new or revised computational theory able to extract useful information from the massive volumes of data collected at an accelerating pace. In fact, besides the traditional measurements, digital data obtained from images, text, audio, sensors, etc complement the survey. Then, we review the different and most popular methodologies among the practitioners of Data Science research and applications. In addition, because the emerging field requires personnel with new competences, we attempt to describe the Data Scientist profile, one of the sexiest jobs of the 21st Century according to Davenport and Patil. Most people are aware of the need to embrace Data Science, but they feel intimidated that they do not understand it and they worry that their jobs will disappear. We want to encourage them: Data Science is more likely to add value to jobs and enrich the lives of working people by helping them make better, more informed business decisions. We conclude this paper by presenting examples of Data Science in action in business and industry, to demonstrate the collection of specialist skills that must come together for this new science to be effective.
Getting Off to a Shaky Start: Specificity in Planning and Feedforward Control During Sensorimotor Learning in Autism Spectrum Disorder
Authors: Foster Nathan C. , Bennett Simon J. , Causer Joe , Elliott Digby , Bird Geoffrey , Hayes Spencer J.
Published: October 2019

Whilst autistic individuals develop new internal action models during sensorimotor learning, the acquired movements are executed less accurately and with greater variability. Such movement profiles are related to differences in sensorimotor integration and/or altered feedforward/feedback sensorimotor control. We investigated the processes underlying sensorimotor learning in autism by quantifying accuracy and variability, relative timing, and feedforward and feedback control. Although autistic individuals demonstrated significant sensorimotor learning across trials, which was facilitated by processing knowledge‐of‐results feedback, motor execution was less accurate than non‐autistic individuals. Kinematic analysis indicated that autistic individuals showed significantly greater spatial variability at peak acceleration, but comparable spatial variability at peak velocity. These kinematic markers suggest that autistic movement profiles are driven by specific differences in sensorimotor control processes (i.e., internal action models) associated with planning and regulating the forces required to execute the movement. The reduction of variability at peak velocity indicates intact early feedback‐based sensorimotor control in autism. Understanding how feedforward and feedback‐based control processes operate provides an opportunity to explore how these control processes influence the acquisition of socio‐motor actions in autism. Autism Res 2020, 13: 423–435. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

Autistic adults successfully learned a new movement skill by physically practising it, and using feedback about how well they had done to become more accurate. When looking at the movements in detail, autistic adults were more variable than non‐autistic adults when planning (e.g., how much force to use), and performing, the movement. These differences impact how autistic individuals learn different types of movement skills, which might influence how other behaviours (e.g., imitation) are acquired that support social interaction.
Why Do Intravascular Schistosomes Coat Themselves in Glycolytic Enzymes?
Authors: Pirovich David , Da'dara Akram A. , Skelly Patrick J.
Published: October 2019

Schistosomes are intravascular parasitic helminths (blood flukes) that infect more than 200 million people globally. Proteomic analysis of the tegument (skin) of these worms has revealed the surprising presence of glycolytic enzymes on the parasite's external surface. Immunolocalization data as well as enzyme activity displayed by live worms confirm that functional glycolytic enzymes are indeed expressed at the host–parasite interface. Since these enzymes are traditionally considered to function intracellularly to drive glycolysis, in an extracellular location they are hypothesized to engage in novel “moonlighting” functions such as immune modulation and blood clot dissolution that promote parasite survival. For instance, several glycolytic enzymes can interact with plasminogen and promote its activation to the thrombolytic plasmin; some can inhibit complement function; some induce B cell proliferation or macrophage apoptosis. Several pathogenic bacteria and protists also express glycolytic enzymes externally, suggesting that moonlighting functions of extracellular glycolytic enzymes can contribute broadly to pathogen virulence. Also see the video abstract here https://youtu.be/njtWZ2y3k_I
Extensions of the probabilistic ranking metrics of competing treatments in network meta‐analysis to reflect clinically important relative differences on many outcomes
Authors: Mavridis Dimitris , Porcher Raphaël , Nikolakopoulou Adriani , Salanti Georgia , Ravaud Philippe
Published: October 2019

One of the key features of network meta‐analysis is ranking of interventions according to outcomes of interest. Ranking metrics are prone to misinterpretation because of two limitations associated with the current ranking methods. First, differences in relative treatment effects might not be clinically important and this is not reflected in the ranking metrics. Second, there are no established methods to include several health outcomes in the ranking assessments. To address these two issues, we extended the P‐score method to allow for multiple outcomes and modified it to measure the mean extent of certainty that a treatment is better than the competing treatments by a certain amount, for example, the minimum clinical important difference. We suggest to present the tradeoff between beneficial and harmful outcomes allowing stakeholders to consider how much adverse effect they are willing to tolerate for specific gains in efficacy. We used a published network of 212 trials comparing 15 antipsychotics and placebo using a random effects network meta‐analysis model, focusing on three outcomes; reduction in symptoms of schizophrenia in a standardized scale, all‐cause discontinuation, and weight gain.
A systematic literature review of socially responsible investment and environmental social governance metrics
Authors: Widyawati Luluk
Published: October 2019

Socially responsible investment (SRI) encompasses both ethical and financial paradigms. This systematic literature review explores three key research themes within the SRI literature, identifying a significant disconnect between themes and a fixation on the financial (as opposed to ethical) paradigm. One of the foundations of SRI is environmental, social, and governance (ESG) metrics. This review confirms the importance of ESG metrics in the SRI field, as they play two crucial roles, namely, as a proxy for sustainability performance and an enabler of the SRI market. However, there are two main issues related to ESG metrics that undermine their reliability: a lack of transparency and a lack of convergence.
Understanding the mechanism of copurification of “difficult to remove” host cell proteins in rituximab biosimilar products
Authors: Singh Sumit K. , Mishra Avinash , Yadav Divyanshi , Budholiya Niharika , Rathore Anurag S.
Published: October 2019

Host cell proteins (HCPs) are considered a critical quality attribute and are linked to safety and efficacy of biotherapeutic products. Researchers have identified 10 HCPs in Chinese hamster ovary (CHO) that exhibit common characteristics of product association, coelution, and age‐dependent expression and therefore are “difficult to remove” during downstream purification. These include cathepsin D, clusterin, galectin‐3‐binding protein, G‐protein coupled receptor 56, lipoprotein lipase, metalloproteinase inhibitor, nidogen‐1 secreted protein acidic and rich in cysteine (SPARC), sulfated glycoprotein, and insulin‐like growth factor‐2 RNA‐binding protein. While the levels of HCPs in the investigated biosimilars were within the acceptable range of <100 ppm, certain “difficult to remove” HCPs were found in the biosimilar samples. This article aims to elucidate the underlying interactions between these “difficult to remove” HCPs and the mAb product. Surface study of rituximab exhibited unstable discontinuous patches of residues on the protein surface that have high propensity to get buried and lower the solvent exposed area. The higher order structure and the receptor binding were not affected, except for one of the biosimilars, owing to extremely low‐HCP levels in its final drug product. Finally, based on the combined experimental and computational data from this study, a probable mechanism of retention for the 10 HCPs is proposed. The results presented here can guide downstream process design or avenues for protein engineering during product discovery to achieve more effective removal of the impurities.
Acid lactic lactobacilli as a biotechnological toll to improve food quality and human health
Authors: Sousa Márcio A. de , Rama Gabriela Rabaioli , Volken de Souza Claucia F. , Granada Camille E.
Published: October 2019

The genus Lactobacillus has been widely used in food industry as starter or adjunct culture due to its probiotic features. Its biotechnological features improve the spectrum of uses of lactobacilli, which can affect its applicability directly. In this sense, this literature review gathers information and discusses the biotechnological potential of technological/probiotic lactobacilli aiming to improve food quality and human health. The primary and secondary metabolism generates specific substances, such as organic acids, carbon dioxide, hydrogen peroxide, diacetyl, fatty acids, and bacteriocins, which are determinant due to their probiotic potential, antimicrobial activity, and the development of new food flavors. In order to become industrially and commercially attractive, it is necessary develop a large‐scale process with lower production costs.
Reliable Methods for Analyses of Volatile Compounds of Copaifera Oleoresins Combining Headspace and Gas Chromatography
Authors: Mangabeira da Silva Jonas Joaquim , Pena Ribeiro Victor , Lemos Marivane , Miller Crotti Antônio Eduardo , Rogez Hervé , Kenupp Bastos Jairo
Published: October 2019

Two analytical methods were developed in this study for direct and fast chemical investigation of authentic Copaifera oleoresins (COR) and commercial products. Polydimethylsiloxane microfiber coupled to gas chromatography‐mass spectrometry (HS‐SPME‐GC/MS) showed the best results for oleoresin qualitative analysis, setting the following extraction conditions: equilibrium time of 15 min, extraction time of 30 min, extraction temperature at 60 °C and constant stirring of 400 rpm. Sesquiterpenes α‐copaene, β‐elemene, β‐caryophyllene and trans‐α‐bergamotene were found in all investigated samples. Quantitative analysis by gas chromatography coupled with flame ionization detector (GC‐FID) measured the content of the four sesquiterpenes in all samples. Qualitative and quantitative results showed important differences between COR of distinct species and commercial products. Data regarding the volatile composition of C. oblongifolia and C. trapezifolia oleoresins were first presented in this study and two new analytical methods were reported for direct and fast qualitative and quantitative analysis of COR.
Antiureolytic Activity of Substituted 2,5‐Diaminobenzoquinones
Authors: Nain‐Perez Amalyn , Barbosa Luiz C. A. , Rodríguez‐Hernández Diego , Mota Yane C. C. , Silva Thamara F. , Ramalho Teodorico C. , Modolo Luzia V.
Published: October 2019

A series of 2,5‐bis(alkyl/arylamino)‐1,4‐benzoquinones (1–12) were investigatedin vitrofor their potential to inhibit the activity of jack bean urease. Compounds1–6,8,9,11and12effectively inhibited the jack bean urease activity by 90.8 % when tested at 5 μm, whereas7and10had relatively little effect. The IC50for most compounds was in the nanomolar range (31.4 nmand 36.0 nmfor2and8, respectively). The mechanism of enzyme inhibition shown by2and8is typical of mixed‐type inhibitors, whose affinity for the active site is over 6‐ and 2‐fold higher (Ki=30.0 and 22.8 nm, for2and8, respectively) than that of an allosteric site. Molecular docking studies revealed that both2and8establish hydrogen bonds with the amino acids residues Asp494, Met588, His593 and Ala636 in the active site of jack bean urease. These results indicate that such aminoquinones are useful leads for the development of more efficient urease inhibitors of wider utility.
Ultrasound controlled paclitaxel releasing system—A novel method for improving the availability of coronary artery drug coated balloon
Authors: Song Caixia , Zhou Chao , Zhang Junwei , Feng Xiangyi , Cui Xiaoshan , Zhang Feng , Ma Jianying , Toft Egon Steen , Ge Junbo , Zhang Haijun
Published: October 2019

Objectives

The aim of this study is to improve local‐drug delivery efficiency and tissue absorption using the ultrasound (US)‐responsible drug coating based on a newly developed US‐controlled paclitaxel release balloon.

Background

Low availability of the drug coating remains a major concern of the current drug coated balloon (DCB). The goal of this study is to develop a method to use an US‐responsible paclitaxel‐loaded microcapsules (PM) as the main content of balloon drug coating to enhance bioavailability of DCB.

Methods

An US‐controlled paclitaxel release balloon is designed and fabricated based on the US‐responsible paclitaxel‐loaded poly (lactic‐co‐glycolic acid) (PLGA) microcapsules. Rapid exchange percutaneous transluminal coronary angioplasty (PTCA) balloon catheters were coated with the PM. The deployment processes of the paclitaxel‐loaded microcapsules coated balloons (PMCB) under US, PMCB without US and a homogenous matrix of paclitaxel and iopromide coated balloon (PICB) were then placed in healthy and stent implanted porcine coronary arteries.

Results

In vitro release assay demonstrated an ability of US (1 MHz, 1.22 W/cm2, 1 minute) to affect the release kinetics of paclitaxel from PM by inducing a 76 ± 5.4% increase in the rate of release. The paclitaxel content in target vessels are 203 ± 37 μg/g for PMCB under US, 85 ± 23 μg/g for PMCB without US, and 107 ± 31 μg/g for PICB 1‐hr post‐surgery. The availability of the drug for the PMCB reaches 27% under US.

Conclusions

The US‐controlled paclitaxel release balloon significantly improved the drug content of the target vessels in the porcine model.
Stereoselective Biotransformations of Cyclic Imines in Recombinant Cells of Synechocystis sp. PCC 6803
Authors: Büchsenschütz Hanna C. , Vidimce‐Risteski Viktorija , Eggbauer Bettina , Schmidt Sandy , Winkler Christoph K. , Schrittwieser Joerg H. , Kroutil Wolfgang , Kourist Robert
Published: October 2019

Light‐driven biotransformations in recombinant cyanobacteria allow to employ photosynthetic water‐splitting for cofactor‐regeneration and thus, to save the use of organic electron donors. The genes of three recombinant imine reductases (IREDs) were expressed in the cyanobacterium Synechocystis sp. PCC 6803 and eight cyclic imine substrates were screened in whole‐cell biotransformations. While initial reactions showed low to moderate rates, optimization of the reaction conditions in combination with promoter engineering allowed to alleviate toxicity effects and achieve full conversion of prochiral imines with initial rates of up to 6.3 mM h−1. The high specific activity of up to 22 U gCDW−1 demonstrates that recombinant cyanobacteria can provide large amounts of NADPH during whole cell reactions. The excellent optical purity of the products with up to >99 %ee underlines the usefulness of cyanobacteria for the stereoselective synthesis of amines.
Fabrication of Bi2WO6/Cu/WO3 All‐Solid‐State Z‐Scheme Composite Photocatalyst to Improve CO2 Photoreduction under Visible Light Irradiation
Authors: Wen Teh Yee , Wei Goh Yien , Ying Kong Xin , Ng Boon‐Junn , Yong Siek‐Ting , Chai Siang‐Piao
Published: October 2019

Photocatalysis has been widely explored to alleviate the high atmospheric CO2 content by converting CO2 into energy‐rich fuels. Bi2WO6 shows great potential in photocatalysis due to its high chemical stability, non‐toxicity and appropriate band position. However, the CH4 yield from CO2 photoreduction over bulk Bi2WO6 is relatively low ascribed to its single‐component structure. Inspired by natural photosynthesis, Z‐scheme system with photosystem I (PS I)‐photosystem II (PS II) coupling via an electron mediator can improve charge separation and at the same time, renders large overpotential, attributed to the vectorial electron transfer from PS II to PS I. In this contribution, an all‐solid‐state Z‐scheme photocatalyst that is composed of 2D Bi2WO6 nanosheets coupled with WO3 along with the incorporation of copper foil sheet as the electron mediator is designed to improve the CO2 reduction efficiency. The Bi2WO6/Cu/WO3 composite demonstrated a remarkable CH4 yield of 8.80 μmol g−1catalyst over 8 hours of visible light illumination, which is superior to the Bi2WO6 standalone.
Improving the Switching Capacity of Glyco‐Self‐Assembled Monolayers on Au(111)
Authors: Fast Ellen , Schlimm Alexander , Lautenschläger Irene , Clausen Kai Uwe , Strunskus Thomas , Spormann Carina , Lindhorst Thisbe K. , Tuczek Felix
Published: October 2019

Self‐assembled monolayers (SAMs) decorated with photoisomerizable azobenzene glycosides are useful tools for investigating the effect of ligand orientation on carbohydrate recognition. However, photoswitching of SAMs between two specific states is characterized by a limited capacity. The goal of this study is the improvement of photoswitchable azobenzene glyco‐SAMs. Different concepts, in particular self‐dilution and rigid biaryl backbones, have been investigated. The required SH‐functionalized azobenzene glycoconjugates were synthesized through a modular approach, and the respective glyco‐SAMs were fabricated on Au(111). Their photoswitching properties have been extensively investigated by applying a powerful set of methods (IRRAS, XPS, and NEXAFS). Indeed, the combination of tailor‐made biaryl‐azobenzene glycosides and suitable diluent molecules led to photoswitchable glyco‐SAMs with a significantly enhanced and unprecedented switching capacity.
Platinum Oxide Nanoparticles for Electrochemical Hydrogen Evolution: Influence of Platinum Valence State
Authors: Nichols Forrest , Lu Jia En , Mercado Rene , Dudschus Ryan , Bridges Frank , Chen Shaowei
Published: October 2019

Electrochemical hydrogen generation is a rising prospect for future renewable energy storage and conversion. Platinum remains a leading choice of catalyst, but because of its high cost and low natural abundance, it is critical to optimize its use. In the present study, platinum oxide nanoparticles of approximately 2 nm in diameter are deposited on carbon nitride (C3N4) nanosheets by thermal refluxing of C3N4 and PtCl2 or PtCl4 in water. These nanoparticles exhibit apparent electrocatalytic activity toward the hydrogen evolution reaction (HER) in acid. Interestingly, the HER activity increases with increasing Pt4+ concentration in the nanoparticles, and the optimized catalyst even outperforms commercial Pt/C, exhibiting an overpotential of only −7.7 mV to reach the current density of 10 mA cm−2 and a Tafel slope of −26.3 mV dec−1. The results from this study suggest that the future design of platinum oxide catalysts should strive to maximize the Pt4+ sites and minimize the formation of the less active Pt2+ species.
Iris‐based continuous authentication in mobile ad hoc network
Authors: Ramkumar D. , Annadurai C. , Nelson I.
Published: October 2019

Mobile Ad hoc Networks (MANETs) are temporary in nature, with security concerns being more vulnerable than the other types of networks. Most of the works concentrate on either authentication or intrusion detection. This framework considers both intrusion detection and authentication continuously. It has been done for different layers of security for finding the intruder and eliminate from the network. Iris images have been used in this work for the purpose of authentication. Detection and response engines have been used for intrusion detection and high security in ad hoc network. The simulation results clearly show the iris‐based continuous authentication detecting most of the intruders and eliminates from the network.
Traditional Chinese medicine foot bath combined with acupoint massage for the treatment of diabetic peripheral neuropathy: A systematic review and meta‐analysis of 31 RCTs
Authors: Fu Qinwei , Yang Hui , Zhang Lanzhi , Liu Yang , Li Xinrong , Dai Menglin , Yang Yepeng , Yang Shasha , Xie Yan , Liu Ying , Fu Li , Liu Zhiqing , Zhang Qinxiu
Published: October 2019

In this study, we aim to evaluate the efficiency and safety of traditional Chinese medicine foot bath combined with acupoint massage for the treatment of diabetic peripheral neuropathy. A total of eight online databases were searched to collect studies published up to February 2019. Study quality of each included article was evaluated by the Cochrane Collaboration risk of bias tool. Systematic reviews and meta‐analyses were conducted based on the Cochrane systematic review method by using the RevMan 5.3 software. Traditional Chinese medicine foot bath combined with acupoint massage was the main therapy in experimental group. Interventions in control groups include western medicine, oral traditional Chinese medicine, other symptomatic treatment of western medicine, and blank control. Primary outcomes in this study include sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), total effective rate, and neuropathic syndrome score. Finally, 31 trials involving 3284 participants were included. The results of systematic reviews and meta‐analyses showed that traditional Chinese medicine foot bath combined with acupoint massage was significantly better compared with the control groups in terms of the total effective rate, SNCV, MNCV, and neuropathic syndrome score. No case of adverse effect was reported. These findings show that traditional Chinese medicine foot bath combined with acupoint massage may be safer and more effective for the treatment of DPN. However, due to the low methodological quality, further research with randomized controlled trials (RCTs) of higher quality is required to prove its efficacy and better evidence for clinical treatment.
Responses of zooplankton body size and community trophic structure to temperature change in a subtropical reservoir
Authors: Gao Xiaofei , Chen Huihuang , Govaert Lynn , Wang Wenping , Yang Jun
Published: October 2019

Understanding the effects of global warming on trait variation and trophic structure is a crucial challenge in the 21st century. However, there is a lack of general patterns that can be used to predict trait variation and community trophic structure under the ongoing environmental change. We investigated the responses of body size and community trophic structure of zooplankton to climate related factors (e.g., temperature). Isotopic niche breadth was applied to investigate the community trophic structure across a 1‐year study from a subtropical reservoir (Tingxi Reservoir) in southeastern China. Body size and community isotopic niche breadth of zooplankton were larger during water mixing than stratification periods and correlated significantly with water temperature change along the time series. The contributions of intra‐ and intertaxonomic components to body size and community trophic structure variation showed significant relationships with the temperature change going from the mixing to stratification periods. Water temperature imposed direct effect on body size, while direct and indirect effect on the community trophic structure of zooplankton occurred through trophic redundancy along time series. Water temperature and community properties (e.g., body size, trophic redundancy, or trophic interaction) showed complex interactions and integrated to influence community trophic structure of zooplankton. Our results can expand the knowledge of how elevated temperature will alter individual trait and community trophic structure under future climate change.
Evolution and disappearance of sympatric Coregonus albula in a changing environment—A case study of the only remaining population pair in Sweden
Authors: Delling Bo , Palm Stefan
Published: October 2019

During the past 50 years, Fennoscandian populations of spring‐spawning Baltic cisco (Coregonus albula), sympatric to common autumn‐spawners, have declined or disappeared; for example, three out of four known spring‐spawning populations in Sweden are regarded as extinct. Over the same period, the climate has changed and populations have been subject to other anthropogenic stressors. We compared historic (1960s) and recent (1990–2000s) morphological data from the still‐existent sympatric cisco populations in Lake Fegen, Sweden. Phenotypic changes were found for spring‐spawners making them more similar to the sympatric autumn‐spawners that had remained virtually unchanged. Based on results for other salmoniform fishes, a phenotypically plastic response to increased temperature during early development appears unlikely. The recent material was also analyzed with microsatellite markers; long‐term effective population size in spring‐spawners was estimated to be about 20 times lower than autumn‐spawners, with signs of long‐term gene flow in both directions and a recent genetic bottleneck in spring‐spawners. We suggest the change toward a less distinct phenotype in spring‐spawners to reflect a recent increase in gene flow from autumn‐spawners. Time since divergence was estimated to only c. 1,900 years (95% CI: 400–5,900), but still the Fegen populations represent the most morphologically and genetically distinct sympatric populations studied. Consequently, we hypothesize that less distinct population pairs can be even younger and that spring‐spawning may have repeatedly evolved and disappeared in several lakes since the end of the last glaciation, concurrent with changed environmental conditions.
Has gene expression neofunctionalization in the fire ant antennae contributed to queen discrimination behavior?
Authors: Dang Viet‐Dai , Cohanim Amir B. , Fontana Silvia , Privman Eyal , Wang John
Published: October 2019

Queen discrimination behavior in the fire ant Solenopsis invicta maintains its two types of societies: colonies with one (monogyne) or many (polygyne) queens, yet the underlying genetic mechanism is poorly understood. This behavior is controlled by two supergene alleles, SB and Sb, with ~600 genes. Polygyne workers, having either the SB/SB or SB/Sb genotype, accept additional SB/Sb queens into their colonies but kill SB/SB queens. In contrast, monogyne workers, all SB/SB, reject all additional queens regardless of genotype. Because the SB and Sb alleles have suppressed recombination, determining which genes within the supergene mediate this differential worker behavior is difficult. We hypothesized that the alternate worker genotypes sense queens differently because of the evolution of differential expression of key genes in their main sensory organ, the antennae. To identify such genes, we sequenced RNA from four replicates of pooled antennae from three classes of workers: monogyne SB/SB, polygyne SB/SB, and polygyne SB/Sb. We identified 81 differentially expressed protein‐coding genes with 13 encoding potential chemical metabolism or perception proteins. We focused on the two odorant perception genes: an odorant receptor SiOR463 and an odorant‐binding protein SiOBP12. We found that SiOR463 has been lost in the Sb genome. In contrast, SiOBP12 has an Sb‐specific duplication, SiOBP12b′, which is expressed in the SB/Sb worker antennae, while both paralogs are expressed in the body. Comparisons with another fire ant species revealed that SiOBP12b′ antennal expression is specific to S. invicta and suggests that queen discrimination may have evolved, in part, through expression neofunctionalization.