bluuebunny/crossref_metadata_2025 huggingface dataset:
A Two‐Stage Dissociation System for Multilayer Imaging of Cancer Biomarker‐Synergic Networks in Single Cells
Authors: Qian Ruo‐Can , Cao Yue , Zhao Li‐Jun , Gu Zhen , Long Yi‐Tao
Published: March 2017

The monitoring of cancer biomarkers is crucial to the early detection of cancer. However, a limiting factor in biomarker analysis is the ability to obtain the multilayered information of various biomarker molecules located at different parts of cells from the plasma membrane to the cytoplasm. A two‐stage dissociation nanoparticle system based on multifunctionalized polydopamine‐coated gold nanoparticles (Au@PDA NPs) is reported, which allows for the two‐stage imaging of cancer biomarkers in single cells. We demonstrate the feasibility of this strategy on sialic acids (SAs), p53 protein, and microRNA‐21 (miRNA‐21) in MCF‐7 breast cancer cells by two custom‐built probes. Furthermore, the multicolor fluorescence information extracted is used for the monitoring of biomarker expression changes under different drug combinations, which allows us to investigate the complex interactions between various cancer biomarkers and to describe the cancer biomarker‐synergic networks in single cells.
The Lightest Element Phosphoranylidene: NHC‐Supported Cyclic Borylidene–Phosphorane with Significant B=P Character
Authors: Rosas‐Sánchez Alfredo , Alvarado‐Beltran Isabel , Baceiredo Antoine , Hashizume Daisuke , Saffon‐Merceron Nathalie , Branchadell Vicenç , Kato Tsuyoshi
Published: March 2017

A borylidene–phosphorane, the lightest phosphoranylidene, which is stabilized by an N‐heterocyclic carbene ligand, was synthesized and fully characterized. Experimental electron density analysis and DFT calculations indicate an enhanced ylene character (rather than an ylide character) with an exceptionally strong B→P π‐back bonding related to the less electronegative boron compared to phosphorus.
A Biomimetic Phosphatidylcholine‐Terminated Monolayer Greatly Improves the In Vivo Performance of Electrochemical Aptamer‐Based Sensors
Authors: Li Hui , Dauphin‐Ducharme Philippe , Arroyo‐Currás Netzahualcóyotl , Tran Claire H. , Vieira Philip A. , Li Shaoguang , Shin Christina , Somerson Jacob , Kippin Tod E. , Plaxco Kevin W.
Published: March 2017

The real‐time monitoring of specific analytes in situ in the living body would greatly advance our understanding of physiology and the development of personalized medicine. Because they are continuous (wash‐free and reagentless) and are able to work in complex media (e.g., undiluted serum), electrochemical aptamer‐based (E‐AB) sensors are promising candidates to fill this role. E‐AB sensors suffer, however, from often‐severe baseline drift when deployed in undiluted whole blood either in vitro or in vivo. We demonstrate that cell‐membrane‐mimicking phosphatidylcholine (PC)‐terminated monolayers improve the performance of E‐AB sensors, reducing the baseline drift from around 70 % to just a few percent after several hours in flowing whole blood in vitro. With this improvement comes the ability to deploy E‐AB sensors directly in situ in the veins of live animals, achieving micromolar precision over many hours without the use of physical barriers or active drift‐correction algorithms.
A Reversible Fluorescent Probe for Real‐Time Quantitative Monitoring of Cellular Glutathione
Authors: Liu Zhixue , Zhou Xin , Miao Yu , Hu Ying , Kwon Nahyun , Wu Xue , Yoon Juyoung
Published: March 2017

The ability to monitor and quantify glutathione (GSH) in live cells is essential in order to gain a detailed understanding of GSH‐related pathological events. However, owing to their irreversible response mechanisms, most existing fluorescent GSH probes are not suitable for this purpose. We have developed a ratiometric fluorescent probe (QG‐1) for quantitatively monitoring cellular GSH. The probe responds specifically and reversibility to GSH with an ideal dissociation constant (Kd) of 2.59 mm and a fast response time (t1/2=5.82 s). We also demonstrate that QG‐1 detection of GSH is feasible in a model protein system. QG‐1 was found to have extremely low cytotoxicity and was applied to determine the GSH concentration in live HeLa cells (5.40±0.87 mm).
Importance of Inherent Substrate Reactivity in Enzyme‐Promoted Carbocation Cyclization/Rearrangements
Authors: Tantillo Dean J.
Published: March 2017

The importance of inherent substrate reactivity for terpene synthase enzymes is discussed, with a focus on recent experimental tests of predictions derived from computations on gas‐phase reactivity of carbocations.
A bicistronic vector with destabilized mRNA secondary structure yields scalable higher titer expression of human neurturin in E. coli
Authors: Roy Varnika , Roth Robert , Berge Mark , Chitta Rajesh , Vajrala Sucheta , Kuntumalla Srilatha , E. Schmelzer Albert , Schoner Ron
Published: March 2017

Human neurturin (NTN) is a cystine knot growth factor with potential therapeutic use in diseases such as Parkinson's and diabetes. Scalable high titer production of native NTN is particularly challenging because of the cystine knot structure which consists of an embedded ring comprised of at least three disulfide bonds. We sought to pursue enhanced scalable production of NTN in Escherichia coli. Our initial efforts focused on codon optimization of the first two codons following AUG, but these studies resulted in only a marginal increase in NTN expression. Therefore, we pursued an alternative strategy of using a bicistronic vector for NTN expression designed to reduce mRNA secondary structure to achieve increased ribosome binding and re‐initiation. The first cistron was designed to prevent sequestration of the translation initiation region in a secondary conformation. The second cistron, which contained the NTN coding sequence itself, was engineered to disrupt double bonded base pairs and destabilize the secondary structure for ribosome re‐initiation. The ensemble approach of reducing NTN's mRNA secondary structure and using the bicistronic vector had an additive effect resulting in significantly increased NTN expression. Our strain selection studies were conducted in a miniaturized bioreactor. An optimized strain was selected and scaled up to a 100 L fermentor, which yielded an inclusion body titer of 2 g/L. The inclusion bodies were refolded to yield active NTN. We believe that our strategy is applicable to other candidate proteins that are difficult‐to‐express due to stable mRNA secondary structures. Biotechnol. Bioeng. 2017;114: 1753–1761. © 2017 Wiley Periodicals, Inc.
European Pension Funds and Sustainable Development: Trade‐Offs between Finance and Responsibility
Authors: Sievänen Riikka , Rita Hannu , Scholtens Bert
Published: March 2017

Pension funds try to account for sustainable development in their operations. This mainly translates in responsible investing. We investigate how this interacts with the financial objectives. We use a survey of more than 250 pension funds based in 15 European countries. Multinomial logistic regression is used to find out how pension funds trade off sustainable development and financial objectives. Our findings suggest that pension funds that have not included responsibility in their strategy and investments have a clear priority regarding their financial performance. Pension funds who integrate sustainable development in their strategy can bring balance between finance and responsibility. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Examining the effect of managing GHG emissions on business performance
Authors: Capece G , Di Pillo F , Gastaldi M , Levialdi N , Miliacca M
Published: March 2017

Unprecedented climate changes menace not only the planetary ecosystem, but also the stability of the global economy. The European Union has for years promoted the transition of the economy towards a model of sustainable development, stimulating companies to adopt a strategic approach based on quality and environmental efficiency, rather than on quantity and reduction of costs.

The aim of this study is to analyze how greater attention to the environmental effects of a company's activities (environmental management) and monitoring and reduction of CO2 emissions (emission management) can improve the company's economic performance. We analyze the financial data and greenhouse gas (GHG) emission figures for a sample of large Italian companies, searching for potential relations between increasing returns on capital invested and the reduction of pollutants. The results show that the companies examined are ever more attentive to environmental policies, and that those with a green vision achieve better operating performance. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Design and evaluation of reduced marker layouts for hand motion capture
Authors: Schröder Matthias , Waltemate Thomas , Maycock Jonathan , Röhlig Tobias , Ritter Helge , Botsch Mario
Published: March 2017

We present a method for automatically generating reduced marker layouts for marker‐based optical motion capture of human hands. The employed motion reconstruction method is based on subspace‐constrained inverse kinematics, which allows for the recovery of realistic hand movements even from sparse input data. We additionally present a user‐specific hand model calibration procedure that fits an articulated hand model to point cloud data of the user's hand. Our marker layout optimization is sensitive to the kinematic structure and the subspace representations of hand articulations utilized in the reconstruction method, in order to generate sparse marker configurations that are optimal for solving the constrained inverse kinematics problem. We propose specific quality criteria for reduced marker sets that combine numerical stability with geometric feasibility of the resulting layout. These criteria are combined in an objective function that is minimized using a specialized surface‐constrained particle swarm optimization scheme, which generates marker layouts bound to the surface of an animated hand model. Our method provides a principled way for determining reduced marker layouts based on subspace representations of hand articulations. We demonstrate the effectiveness of our motion reconstruction and model calibration methods in a thorough evaluation.
Use of four‐factor prothrombin complex concentrate for the mitigation of rivaroxaban‐induced bleeding in an emergent coronary artery bypass graft
Authors: Liu Michael , Aguele Cliff , Darr Umer
Published: March 2017

Key Clinical Message

We presented the first case of four‐factor prothrombin complex concentrate (4F‐PCC) for the alleviation of bleeding for emergent on‐pump coronary artery bypass graft (CABG) with the patient discharged by postoperative day (POD) 9 with no sequelae. Until direct antidotes are available, 4F‐PCC may play a role in the management of mitigating rivaroxaban‐induced bleeding in surgical procedure.
Odontogenic cutaneous fistula mimicking malignancy
Authors: Baba Akira , Okuyama Yumi , Shibui Takeo , Ojiri Hiroya
Published: March 2017

Key Clinical Message

It is important for the dentists to make accurate diagnosis and appropriate treatment of odontogenic cutaneous fistula. Although large facial skin lesions may bring up malignancy on top of the differential list, careful evaluation including physical observation, imaging, and pathology can rule out malignancies.
A Multi‐Stream Microchip for Process Intensification of Liquid‐Liquid Extraction
Authors: Kriel Frederik H. , Binder Claudia , Priest Craig
Published: March 2017

Solvent extraction is a critical step in many industrial mineral‐processing circuits and is affected by chemical (e.g., metal ions, extractant, pH, reaction rate) and physical (e.g., interfacial phenomena, mass transport, temperature) factors. Here, a new type of microfluidic contactor is presented that enables higher volumetric throughputs and straightforward counter‐current operation compared with Y‐Y chips. A single chip design can handle a wide range of organic/aqueous phase ratios, thereby enabling stable operation for non‐ideal solutions and fluctuating flow. An expression defining this widened operational window has been derived based on the relative stream geometries and liquid viscosities. A two‐stage counter‐current circuit is demonstrated for the extraction of platinum(IV) chloride.
A Reinterpretation of the Crystal Structure Analysis of [K(crypt‐222)]+CF3−: No Proof for the Trifluoromethanide Ion
Authors: Becker Sabine , Müller Peter
Published: March 2017

Critically discussing and, if necessary, questioning results presented by other researchers has always been a vitally important process in science. Only through fruitful discourse does science arrive at broadly accepted hypotheses that finally become what we accept as scientific truth. In the spirit of this time‐honored tradition, we have examined the crystal structure as well as X‐ray diffraction data of the proposed compound [K(crypt‐222)]+CF3−, which has recently been published. We arrived at the conclusion that the claim of the authors to have successfully and unambiguously characterized the ionic [K(crypt‐222)]+CF3− through single‐crystal X‐ray diffraction is not sustainable. Even though it is possible that the original authors have indeed encountered the proposed species, the purpose of this report is to point out that the original authors cannot use the presented crystallographic data and model as proof for the existence of [K(crypt‐222)]+CF3−. The reason for our conclusion is two‐fold: firstly, the crystal structure was not refined to established standards of good crystallographic practice and secondly, even if best practices of structure determination are employed, the submitted diffraction data do not allow establishing conclusively the true nature of the compound at hand. Recognizing that this gives charge unbalance we have not resolved, we nevertheless suggest an alternative molecular model, [K(crypt‐222)]⋅CHF3, to demonstrate the ambiguity of the diffraction data submitted by the original authors. However, because of this ambiguity, it is important to point out that the purpose of this report is not (and cannot be) the determination of the true nature of the compound at hand; we would merely like to demonstrate that an alternative interpretation of the original diffraction data is possible and, hence, that the conclusion drawn by the original authors is not unambiguously supported by their own data.
Potassium Nitraminofurazan Derivatives: Potential Green Primary Explosives with High Energy and Comparable Low Friction Sensitivities
Authors: Li Ying , Huang Haifeng , Shi Yameng , Yang Jun , Pan Renming , Lin Xiangyang
Published: March 2017

Lead‐based primary explosives were widely applied in military and civilian ammunition, which have subsequently caused serious environmental and health‐related problems. Therefore, the development of green alternatives for the lead‐based primary explosives has been one of the major focuses in the field of energetic materials. Four potassium salts based on nitraminofurazan have been easily synthesized and show excellent comprehensive performances. Among them, potassium 3‐dinitromethyl‐4‐nitraminofurazan (K2DNMNAF, 1) showed better thermal stability (Td: 281.4 °C), higher density (2.174 g cm−3), and lower friction sensitivities (72 N) than that of potassium 4,5‐bis(dinitromethyl)furoxanate (K2BDNMF, Td: 218.3 °C, density: 2.130 g cm−3, FS: 5 N, P: 27.3 GPa, vD: 7759 m s−1); furthermore, it displayed comparable detonation performances (P: 27.2 GPa, vD: 7758 m s−1). The promising properties of these salts make this kind of material a competitive alternative to lead azide as a primary explosive.
One Versatile Route to Three‐Dimensional Graphene Wrapped Metal Cyanide Aerogels for Enhanced Sodium Ion Storage
Authors: Bu Fanxing , Feng Xiaoxiang , Jiang Tiancai , Shakir Imran , Xu Yuxi
Published: March 2017

Facile and controllable integration of metal cyanides (MCs) into three‐dimensional graphene (3DG) with advantageous structures is of fundamental importance for the development of superior MC‐based electrode materials for electrochemical energy storage and catalysis. Here a facile and versatile spatially‐confined Ostwald ripening strategy was developed to synthesize a series of 3DG wrapped MC aerogels with different compositions, size, and structure based on the chemical instability of MC in the reaction system. Remarkably, the integration of Prussian blue (PB) into 3DG, with such unique architecture, largely improves the rate performance and long‐term cycling stability of PB as a cathode material for sodium ion batteries.
Metal‐Organic Framework Wears a Protective Cover for Improved Stability
Authors: Zhang Tao , Zou Binghua , Shao Meng , Chen Xinyi , Zhang Suoying , Li Linjie , Du Qinjie , Li Hongfeng , Hu Yu , Weng Jiena , Xiong Weiwei , Zheng Bing , Zhang Weina , Huo Fengwei
Published: March 2017

Metal‐organic frameworks (MOFs) with an ordered channel and porosity show great promise for a myriad of purposes. Unfortunately, the coordination bond of metal ions and organic ligands easily weakens in unfavorable environments, which poses a key problem in expanding the application of MOFs. Herein, we report a general and efficient strategy to enhance the stability and preserve the porosity of MOFs by coating them with reduced graphene oxide (rGO). The prepared hybrid material consisted of MOFs and rGO, as the core and the protective shell, respectively. It is worth noting that the obtained MOFs@rGO composite material maintained a well‐defined crystal structure and showed good catalytic activity as well as enhanced stability. Notably, this novel and general method of coating MOFs with a thin protective rGO shell will broaden the application fields of MOFs and open up a new avenue for the research of MOFs.
DNA Three‐Way Junction for Differentiation of Single‐Nucleotide Polymorphisms with Fluorescent Copper Nanoparticles
Authors: Sun Feifei , You Ying , Liu Jie , Song Quanwei , Shen Xiaotong , Na Na , Ouyang Jin
Published: March 2017

A label‐ and enzyme‐free fluorescent sensor for the detection of single‐nucleotide polymorphisms (SNPs) at room temperature is proposed, using new copper nanoparticles (CuNPs) as fluorescent reporters. The CuNPs were constructed by using a DNA three‐way junction (3WJ) template. In this assay, two complementary adenine/thymine‐rich probes can hybridize with the wild‐type target simultaneously to construct a 3WJ structure, serving as an efficient scaffold for the generation of CuNPs. However, the CuNPs produce weak fluorescence when the probes bind with a mutant‐type target. SNPs can be identified by the difference in fluorescence intensity of the CuNPs. This SNPs detection strategy is straightforward, cost‐effective, and avoids the complicated procedures of labeling or enzymatic reactions. The fluorescent sensor is versatile and can be applied to all types of mutation because the probes are programmable. Moreover, the sensor exhibits good detection performance in biological samples.
Color breakup visibility thresholds for 2‐field sequential colors
Authors: Wang Jian , Zhang Yuning , Li Xiaohua , Weng Yishi
Published: March 2017

Nowadays local primary desaturation has been proved to be an effective method to suppress the color breakup for field‐sequential‐color (FSC) displays. However, little attention has been focused on the interaction between various subfield colors and the color breakup visibility. In this article, a perception experiment was conducted with the help of a 120 Hz 2‐field FSC display to investigate the thresholds of color breakup visibility along different hue directions with a constant white point in the standard color space. The experimental results show that the color breakup visibility is various when using different subfield colors for temporal combination. A relative high threshold value or low sensitivity of color breakup visibility can be observed when subfield colors are chosen along the blue‐yellow direction while becoming perceptible easily along magenta‐cyan direction. The results and analysis of our experiments are promising to optimize the performance of local primary desaturation. Meanwhile, other applications using the temporal color fusion such as tunable lighting can also benefit from the conclusion of our work to suppress the color breakup effect.
Using 3dRNA for RNA 3‐D Structure Prediction and Evaluation
Authors: Wang Jian , Xiao Yi
Published: March 2017

This unit describes how to use 3dRNA to predict RNA 3‐D structures from their sequences and secondary (2‐D) structures, and how to use 3dRNAscore to evaluate the predicted structures. The predicted RNA 3‐D structures can be used to predict or understand their functions and can also be used to find the interactions between the RNA and other molecules. © 2017 by John Wiley & Sons, Inc.
Using FunSeq2 for Coding and Non‐Coding Variant Annotation and Prioritization
Authors: Dhingra Priyanka , Fu Yao , Gerstein Mark , Khurana Ekta
Published: March 2017

The identification of non‐coding drivers remains a challenge and bottleneck for the use of whole‐genome sequencing in the clinic. FunSeq2 is a computational tool for annotation and prioritization of somatic mutations in coding and non‐coding regions. It integrates a data context made from large‐scale genomic datasets and uses a high‐throughput variant prioritization pipeline. This unit provides guidelines for installing and running FunSeq2 to (a) annotate and prioritize variants, (b) incorporate user‐defined annotations, and (c) detect differential gene expression. © 2017 by John Wiley & Sons, Inc.
Identifying Significantly Impacted Pathways and Putative Mechanisms with iPathwayGuide
Authors: Ahsan Sidra , Drăghici Sorin
Published: March 2017

iPathwayGuide is a gene expression analysis tool that provides biological context and inferences from data generated by high‐throughput sequencing. iPathwayGuide utilizes a systems biology approach to identify significantly impacted signaling pathways, Gene Ontology terms, disease processes, predicted microRNAs, and putative mechanisms based on the given differential expression signature. By using a novel analytical approach called Impact Analysis, iPathwayGuide considers the role, position, and relationships of each gene within a pathway, which results in a significant reduction in false positives, as well as a better ability to identify the truly impacted pathways and putative mechanisms that can explain all measured gene expression changes. It is a Web‐based, user‐friendly, interactive tool that does not require prior training in bioinformatics. The protocols in this unit describe how to use iPathwayGuide to analyze a single contrast between two phenotypes (any number of samples), and provide guidance on how to interpret the results obtained from iPathwayGuide. Even though iPathwayGuide has powerful meta‐analysis capabilities, these are not covered in this unit. © 2017 by John Wiley & Sons, Inc.
Analyses and techniques for phase noise reduction in CMOS Hartley oscillator topology
Authors: Chlis Ilias , Pepe Domenico , Zito Domenico
Published: March 2017

This paper reports the analyses of the inductive degeneration, noise filter, and optimum current density techniques for phase noise reduction in the CMOS Hartley oscillator circuit topology. The design of the circuit topology is carried out in 28 nm bulk CMOS technology in a range of common conditions adopted also for a previous study on the Colpitts topology, so complementing the previous study on Colpitts topology and allowing a direct comparison between the Hartley and Colpitts topologies. The theoretical analyses of the three techniques are carried out and verified by means of circuit simulations. The results obtained for the inductive degeneration and noise filter show the existence of an optimum inductance for minimum phase noise. Moreover, the results obtained for the optimum bias current density technique applied to a Hartley oscillator circuit topology incorporating either inductive degeneration or noise filter provide the demonstration of the existence of an optimum bias current density for minimum phase noise. Moreover, we will go beyond this important result, by investigating for the first time the relationship with the optimum current density for transistor minimum noise figure and other general results reported in the literature. Overall, the analyses show that the adoption of these techniques may lead to a potential phase noise reduction up to 16 dB at a 1 MHz frequency offset for an oscillation frequency of 10 GHz, with respect to the traditional Hartley topology. Lastly, we report a comparison under common conditions between Colpitts and Hartley topologies implementing the aforementioned techniques, which could, from a designer perspective, be useful to acquiring a few key insights about the circuit design opportunities and focus the design efforts toward specific directions for performance optimizations. Copyright © 2017 John Wiley & Sons, Ltd.
Synthesis of essential‐regular bicubic impedances
Authors: Zhang Sara Ying , Jiang Jason Zheng , Wang Huai Lei , Neild Simon
Published: March 2017

This paper provides a complete realisation of a special class of positive‐real bicubic impedances. The problem is motivated by the concept of the inerter, which is the mechanical dual of a capacitor. This device allows mechanical network synthesis, by completing the electrical mechanical analogy. With mechanical synthesis, the emphasis is to minimise the number of elements required to allow feasible implementation. The definitions of simple‐series‐parallel networks and essential‐regular positive‐real functions are introduced. The simple‐series‐parallel minimum‐reactive networks that can realise all essential‐regular bicubics are identified and grouped into six network quartets. One of the advantages of these networks is that they contain the minimal number of reactive elements. The necessary and sufficient realisability conditions for all these networks, as well as corresponding element values, are then derived. Finally, numerical examples are provided to illustrate the validity of the theoretical results. In the course of the argument, interesting conclusions regarding essential‐regular bilinear and biquadratic functions have also been presented. Copyright © 2017 John Wiley & Sons, Ltd.
Equine performance genes and the future of doping in horseracing
Authors: Wilkin Tessa , Baoutina Anna , Hamilton Natasha
Published: March 2017

A horse's success on the racetrack is determined by genetics, training and nutrition, and their translation into physical traits such as speed, endurance and muscle strength. Advances in genetic technologies are slowly explaining the roles of specific genes in equine performance, and offering new insights into the development of novel therapies for diseases and musculoskeletal injuries that cause early retirement of many racehorses. Gene therapy approaches may also soon provide new means to artificially enhance the physical performance of racehorses. Gene doping, the misuse of gene therapies for performance enhancement, is predicted to be the next phase of doping faced by horseracing. The risk of gene doping to human sports has been recognised for almost 15 years, and the introduction of the first gene doping detection tests for doping control in human athletes is imminent. Gene doping is also a threat to horseracing, but there are currently no methods to detect it. Efficient and accurate detection methods need to be developed to deter those looking to use gene doping in horses and to maintain the integrity of the sport. Methods developed for human athletes could offer an avenue for detection in racehorses. Development of an equine equivalent test will first require identification of equine genes that will likely be targeted by gene doping attempts. This review focuses on genes that have been linked to athletic performance in horses and, therefore, could be targeted for genetic manipulation. The risks associated with gene doping and approaches to detect gene doping are also discussed. Copyright © 2017 John Wiley & Sons, Ltd.
Effect of hydroxytyrosol, walnut and olive oil on nutritional profile of Low‐Fat Chicken Frankfurters
Authors: Nieto Gema , Martínez Lorena , Castillo Julian , Ros Gaspar
Published: March 2017

The aim of this study was to evaluate the effect of hydroxytyrosol extract (HXT, 50 ppm), walnut paste (2.5 g/100 g) and extra olive oil (as substitute of animal fat, 20 g/100 g) on fatty acid profiles, mineral content and sensory analysis of chicken frankfurters. Low‐fat chicken sausages produced with olive oil as fat replacement, walnut and HXT extract remained stable without a significant loss of sensory attributes during storage at 4°C for 21 days. The sausages with HXT were found to decrease rancid odour, and the samples with walnut were darker, compared with control. Whereas positive correlations were established between rancid odour, saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA), and negative correlations were found between polyunsaturated fatty acid (PUFA), rancid odour and thibarbituric acid‐reactive substances (TBARS); no significant correlations were established between TBARS and MUFA. Sausages with walnut or olive oil contained significantly larger (P < 0.05) percentages of minerals (K, Fe, Mg, Mn, Ca, P and Zn), MUFAs, and n3 PUFAs, mainly α‐linolenic acid, in addition to significantly lower amounts (P < 0.05) of SFAs, mainly miristic, palmitic and stearic acid. They also contained a significantly lower n6/n3 PUFA ratio, atherogenic index (AI) and thrombogenicity index (IT) and significantly higher (P < 0.05) PUFA ratio. In conclusion, walnut, HXT and olive oil can be applied in meat products as additives with functional properties.

Practical applications: We designed a new functional meat product using fat replacers, healthy fatty acid source and natural antioxidant. We determine whether the inclusion of walnut is able to improve the fatty acid profile and mineral content of Frankfurters. We determine whether the inclusion of hydroxytyrosol as antioxidant is able to protect the fatty acid of Frankfurters from oxidation during its storage.. Olive oil, hydroxytyrosol and walnut have potential for meat industry as new ingredients during frankfurters manufacturing.

Formulation of chicken frankfurters for the different experimental treatments.
Synthesis and Application of Cyclic Diaryliodonium Salts: A Platform for Bifunctionalization in a Single Step
Authors: Chatterjee Nachiketa , Goswami Avijit
Published: March 2017

In recent years the chemistry of cyclic iodonium salts has experienced ever‐growing development. The advantages of using cyclic iodonium salts over acyclic iodonium salts are that the reactions between cyclic iodonium salts and various nucleophiles lead, under suitable reaction conditions, to dual arylations in a one‐pot manner and to the formation of new heterocycles. Variously functionalized thiophenes, carbazoles, fluorenes, phenanthrenes and triazolophenanthridines have been synthesized by utilizing cyclic diaryliodonium salts. Various new ladder‐type π‐conjugated systems have also been synthesized by employing cyclic iodonium salts. In this microreview, the recent advancements in the synthesis and application of cyclic diaryliodonium salts are discussed in a systematic and concise manner.
Recombinant cells in the lung increase with age via de novo recombination events and clonal expansion
Authors: Kimoto Takafumi , Kay Jennifer E. , Li Na , Engelward Bevin P.
Published: March 2017

Homologous recombination (HR) is a critical DNA repair pathway, which is usually error‐free, but can sometimes lead to cancer‐promoting mutations. Despite the importance of HR as a driver of mutations, the spontaneous frequency of such mutations has proven difficult to study. To gain insight to location, cell type, and subsequent proliferation of mutated cells, we used the Rosa26 Direct Repeat (RaDR) mice for in situ detection and quantification of recombinant cells in the lung. We developed a method for automated enumeration of recombinant cells in lung tissue using the Metafer 4 slide‐scanning platform. The mean spontaneous HR frequencies of the lung tissue in young and aged mice were 2 × 10−6 and 30 × 10−6, respectively, which is consistent with our previous reports that mutated cells accumulate with age. In addition, by using the capability of Metafer 4 to mark the position of fluorescent cells, we found that recombinant cells from the aged mice formed clusters in the lung tissue, likely due to clonal expansion of a single mutant cell. The recombinant cells primarily consisted of alveolar epithelial type II or club (previously known as Clara) cells, both of which have the potential to give rise to cancer. This approach to tissue image analysis reveals the location and cell types that have undergone HR. Being able to quantify mutant cells in situ within lung tissue opens doors to studies of exposure‐induced mutations and clonal expansion, giving rise to new opportunities for understanding how genetic and environmental factors cause tumorigenic mutations. Environ. Mol. Mutagen. 58:135–145, 2017. © 2017 Wiley Periodicals, Inc.
Delay‐ and energy‐aware load balancing in ultra‐dense heterogeneous 5G networks
Authors: Taboada Ianire , Aalto Samuli , Lassila Pasi , Liberal Fidel
Published: March 2017

In the context of ultra‐dense heterogeneous networks in 5G, we focus on the load balancing problem of elastic traffic in a single macrocell that is supported by a number of small cells. Each small cell is modeled by a single‐class processor sharing queue, whereas the macrocell is modelled by a multiclass processor sharing queue. We assume that the macrocell is always consuming energy, while a small cell can be switched off when it is idle with the setup delay penalty. As the main contribution, aimed at minimizing the weighted sum of the mean delay and the mean power consumption in the system, we develop static and dynamic load balancing policies that take into account the setup delay. All the obtained results are analytically founded. The performance of the static policy is evaluated using the achieved analytical expressions, which include the static optimal probabilities achieved before, whereas for the dynamic policy we need to perform simulations using previously obtained numerical results from the first policy iteration procedure. As concluded, numerical results indicate that the dynamic policy outperforms the static policy under realistic settings.
Unknown primary head and neck squamous cell carcinoma in the era of fluorodeoxyglucose‐positron emission tomography/CT and intensity‐modulated radiotherapy
Authors: de Ridder Mischa , Klop Martin , Hamming‐Vrieze Olga , de Boer JanPaul , Jasperse Bas , Smit Laura , Vogel Wouter , van den Brekel Michiel , Al‐Mamgani Abrahim
Published: March 2017

Background

The diagnosis and treatment of head and neck carcinoma of unknown primary (CUP) have changed with the introduction of fluorodeoxyglucose‐positron emission tomography (FDG‐PET)/CT and intensity‐modulated radiotherapy (IMRT), with potential implications for outcome.

Methods

We conducted a retrospective analysis of 80 patients with head and neck CUP who were PET‐staged and treated with curative intention using IMRT between 2006 and 2016 in the Netherlands Cancer Institute. Patient, tumor, and treatment demographics were recorded and oncologic outcomes were analyzed.

Results

Local control was 100% in mucosal irradiated patients. Regional control was 90%. Ten patients developed distant metastases, which were associated with N3, extracapsular extension (ECE) and lower neck positive lymph nodes. Overall survival (OS) at 5 years was 62% and disease‐specific survival was 78%. ECE, N3 neck, multiple levels of positive lymph nodes, and positive lymph nodes in the lower neck were associated with worse prognosis.

Conclusion

Locoregional outcome of head and neck CUP managed with modern techniques is good. Future research needs to focus on reducing toxicity and patients prone for distant metastasis.
Ferritin, cellular iron storage and regulation
Authors: Arosio Paolo , Elia Leonardo , Poli Maura
Published: March 2017

Ferritin is considered the major iron storage protein which maintains a large iron core in its cavity and has ferroxidase activity. There are many types of ferritin particularly in prokaryotes that include the canonical 24‐mer FTN molecules, the heme‐containing BFR, the smaller 12‐mer DPS and the newly recognized EncFtn of encapsulin that forms a very large iron storage compartment. Recent studies show that ferritin function is more dynamic than previous depicted and new mechanisms of ferritin iron recycling are emerging. They participate to the regulation of cellular iron homeostasis as those of ferritin biosynthesis, cooperating also with the iron‐dependent mechanism of cellular iron secretion. Some of these basic processes are in common between unicellular and animal cells, and this review aims at discussing the findings on the connections between iron storage, cellular iron regulation and ferritin iron recycling that have been explored in unicellular organisms and in animals. © 2017 IUBMB Life, 69(6):414–422, 2017
Characterization of SH‐SY5Y human neuroblastoma cell growth over glass and SU‐8 substrates
Authors: Ajetunmobi A. , McAllister D. , Jain N. , Brazil O. , Corvin A. , Volkov Y. , Tropea D. , Prina‐Mello A.
Published: March 2017

The physical properties of substrates can have profound effects on the structure and function of cultured cells. In this study, we aimed to examine the viability, adherence, and morphological and functional variations between SH‐SY5Y human neuroblastoma cells cultured on SU‐8 surfaces compared with control surfaces composed of borosilicate glass, which are routinely used for cell culture. The SU‐8 polymer has been extensively studied for its biocompatibility, but there has been little investigation into the characteristic differences between cells cultured on SU‐8 when compared with glass. SH‐SY5Y cells were cultured within polydimethylsiloxane wells on both SU‐8 and glass substrates for up to 72 h after which flow cytometry and enzyme‐linked immunosorbent assay analysis was performed to examine cell viability and neurotoxicity. Immunocytochemistry was also performed to analyze the morphological and functional characteristics of the cells. Atomic force microscopy was performed to measure surface roughness and to map cell–substrate interactions. Nanoindentation testing was used to characterize the mechanical properties of polymer surface. Results showed that SH‐SY5Y cells grown on SU‐8 have significantly improved viability and increased morphological and functional characteristics of neurodevelopment. The results from this study suggest that the mechanical properties of the polymer are optimal for the study of cultured cell lines, which could account for the increased viability, adherence, and morphological and functional characteristics of neurodevelopment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2129–2138, 2017.
Computational imaging analysis of glycated fibrin gels reveals aggregated and anisotropic structures
Authors: Norton David G. , Fan Natalie K. , Goudie Marcus J. , Handa Hitesh , Platt Manu O. , Averett Rodney D.
Published: March 2017

In this article, a computational imaging analysis method is presented for the evaluation of aggregation and anisotropy in both native (unglycated) and glycated fibrin matrix structures. The imaging analysis was used to test the hypothesis that glycated fibrin structures are more aggregated and anisotropic than unglycated (native) fibrin structures. Glycation of fibrinogen, and subsequently fibrin, occurs under normal physiological conditions; however, excess glycation due to disease states such as diabetes can disrupt the fibrin matrix and cause an abnormal structure and function. Studies that elucidate morphological changes in glucose incubated fibrin matrices are necessary to better understand thrombosis, which occurs due to hypercoagulable conditions. In this study, imaging algorithms were designed for the determination of aggregation of fibrin fibers within a matrix as well as preferential orientation (anisotropy) due to glycation. The results showed that glycated fibrin structures displayed an overall higher degree of aggregation and anisotropy as compared to unglycated fibrin structures. However, for glycated fibrin matrices that were polymerized utilizing extended incubation periods representative of physiological plasma glucose conditions, the results showed that fibrin aggregation and anisotropy decreased when compared to unglycated matrices. The algorithms showed that incorporation of the crosslinking agent FXIII into the fibrin matrix was shown to decrease both aggregation and anisotropy. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2191–2198, 2017.
Exploring the in vitro and in vivo compatibility of PLA, PLA/GNP and PLA/CNT‐COOH biodegradable nanocomposites: Prospects for tendon and ligament applications
Authors: Correia Pinto Viviana , Costa‐Almeida Raquel , Rodrigues Ilda , Guardão Luísa , Soares Raquel , Miranda Guedes Rui
Published: March 2017

Anterior cruciate ligament (ACL) reconstructive surgeries are the most frequent orthopedic procedures in the knee. Currently, existing strategies fail in completely restoring tissue functionality and have a high failure rate associated, presenting a compelling argument towards the development of novel materials envisioning ACL reinforcement. Tendons and ligaments, in general, have a strong demand in terms of biomechanical features of developed constructs. We have previously developed polylactic acid (PLA)‐based biodegradable films reinforced either with graphene nanoplatelets (PLA/GNP) or with carboxyl‐functionalized carbon nanotubes (PLA/CNT‐COOH). In the present study, we comparatively assessed the biological performance of PLA, PLA/GNP, and PLA/CNT‐COOH by seeding human dermal fibroblasts (HFF‐1) and studying cell viability and proliferation. In vivo tests were also performed by subcutaneous implantation in 6‐week‐old C57Bl/6 mice. Results showed that all formulations studied herein did not elicit cytotoxic responses in seeded HFF‐1, supporting cell proliferation up to 3 days in culture. Moreover, animal studies indicated no physiological signs of severe inflammatory response after 1 and 2 weeks after implantation. Taken together, our results present a preliminary assessment on the compatibility of PLA reinforced with GNP and CNT‐COOH nanofillers, highlighting the potential use of these carbon‐based nanofillers for the fabrication of reinforced synthetic polymer‐based structures for ACL reinforcement. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2182–2190, 2017.
Phage‐like packing structures with mean field sequence dependence
Authors: Myers Christopher G. , Pettitt B. Montgomery
Published: March 2017

Packing of double‐stranded DNA in phages must overcome both electrostatic repulsions and the problem of persistence length. We consider coarse‐grained models with the ability to kink and with randomly generated disorder. We show that the introduction of kinking into configurations of the DNA polymer packaged within spherical confinement results in significant reductions of the overall energies and pressures. We use a kink model which has the ability to deform every 24 bp, close to the average length predicted from phage sequence. The introduction of such persistence length defects even with highly random packing models increases the local nematic ordering of the packed DNA polymer segments. Such local ordering allowed by kinking not only reduces the total bending energy of confined DNA due to nonlinear elasticity but also reduces the electrostatic component of the energy and pressure. We show that a broad ensemble of polymer configurations is consistent with the structural data. © 2016 Wiley Periodicals, Inc.
Evaluation of the restricted virtual space approximation in the algebraic‐diagrammatic construction scheme for the polarization propagator to speed‐up excited‐state calculations
Authors: Yang Chong , Dreuw Andreas
Published: March 2017

The applicability and limitations of the restricted virtual space (RVS) approximation within the algebraic‐diagrammatic construction (ADC) scheme for the polarization propagator up to third order is evaluated. In RVS‐ADC, not only the core but also a substantial amount of energetically high‐lying virtual orbitals is restricted in excitation energy calculations of low‐lying excited electronic states. Using octatetraene, indole, and pyridine as representative examples and different standard basis sets of triple‐zeta quality, RVS‐ADC(2) turns out to be highly useful and to have negligible effects on ππ* excited states. However, for nπ* or πσ* states, the RVS approximation is generally less reliable but better at third‐order than second‐order ADC level. In addition, a unified, basis‐set independent, thus normalized virtual orbital threshold (value) is introduced, making the RVS approximation more controllable and a priori applicable. © 2017 Wiley Periodicals, Inc.
Individual‐specific variation in the respiratory activities of HMECs and their bioenergetic response to IGF1 and TNFα
Authors: Schneider Sallie S. , Henchey Elizabeth M. , Sultana Nazneen , Morin Stephanie M. , Jerry D. Joseph , Makari‐Judson Grace , Crisi Giovanna M. , Arenas Richard B. , Johnson Melissa , Mason Holly S. , Yadava Nagendra
Published: March 2017

Metabolic reprograming is a hallmark of cancer cells. However, the roles of pre‐existing differences in normal cells metabolism toward cancer risk is not known. In order to assess pre‐existing variations in normal cell metabolism, we have quantified the inter‐individual variation in oxidative metabolism of normal primary human mammary epithelial cells (HMECs). We then assessed their response to selected cytokines such as insulin growth factor 1 (IGF1) and tumor necrosis factor alpha (TNFα), which are associated with breast cancer risk. Specifically, we compared the oxidative metabolism of HMECs obtained from women with breast cancer and without cancer. Our data show considerable inter‐individual variation in respiratory activities of HMECs from different women. A bioenergetic parameter called pyruvate‐stimulated respiration (PySR) was identified as a key distinguishing feature of HMECs from women with breast cancer and without cancer. Samples showing PySR over 20% of basal respiration rate were considered PySR+ve and the rest as PySR−ve. By this criterion, HMECs from tumor‐affected breasts (AB) and non‐tumor affected breasts (NAB) of cancer patients were mostly PySR−ve (88% and 89%, respectively), while HMECs from non‐cancer patients were mostly PySR+ve (57%). This suggests that PySR−ve/+ve phenotypes are individual‐specific and are not caused by field effects due to the presence of tumor. The effects of IGF1 and TNFα treatments on HMECs revealed that both suppressed respiration and extracellular acidification. In addition, IGF1 altered PySR−ve/+ve phenotypes. These results reveal individual‐specific differences in pyruvate metabolism of normal breast epithelial cells and its association with breast cancer risk.