bluuebunny/crossref_metadata_2025 huggingface dataset:
Scaffolding for Access to Productive Struggle
Authors: Barlow Angela T. , Gerstenschlager Natasha E. , Strayer Jeremy F. , Lischka Alyson E. , Stephens D. Christopher , Hartland Kristin S. , Willingham J. Christopher
Published: January 2018

Examining two lessons using the same problem illuminates a way that scaffolding can support access to productive struggle.
Seven Billion People: Fostering Productive Struggle
Authors: Murawska Jaclyn M.
Published: January 2018

A cognitively demanding real-world task can help shape students' mathematical dispositions.
Supporting All Learners in Productive Struggle
Authors: Townsend Cynthia , Slavit David , McDuffie Amy Roth
Published: January 2018

To support a growth mindset in students, consider components involving cognitive, social, and emotional aspects so that students can work within their zone of productive stuggle.
Sorting to Develop Definitional Reasoning
Authors: Kobiela Marta , Jackson Kara J. , Savard Annie , Shahan Emily
Published: January 2018

All too often, definitions of mathematical ideas and objects are presented as facts to memorize in mathematics classrooms (de Villiers 1998; Keiser 2000). This is unfortunate, as it means that students are not provided opportunities to engage in a form of reasoning that is arguably at the heart of mathematics—definitional reasoning. Making sense of, constructing, and using definitions to determine what counts as an object (e.g., an odd number, a triangle) develop students' ability to communicate about mathematical ideas and their conceptual understanding of properties and relations (Keiser 2000).
Silence in official representations of history: Implications for national identity and intergroup relations
Authors: Kurtiş Tuğçe , Soylu Yalçınkaya Nur , Adams Glenn
Published: January 2018

Dominant representations of history evolve through differential exercise of power to enable memory of collective triumphs and silence memory of collective misdeeds. We examined silence regarding minorities in official constructions of history and the implications of this silence for national identity and intergroup relations in Turkey. A content analysis of official constructions of history inscribed in Turkish national university admissions exams (Study 1) revealed an emphasis on celebratory events, silence about ethnic and religious minorities, and a construction of national identity in ethno-cultural (e.g., as “Turk” and “Muslim”) rather than civic terms (e.g., in terms of citizenship). An investigation with Turkish participants (Study 2) revealed that denial of historical information regarding minority populations documented in sources outside the national curriculum was associated with greater endorsement of ethno-cultural constructions of identity and less support for minority rights and freedom of expression. We discuss the liberatory potential of alternative forms of historical knowledge to promote more inclusive models of identification and improve intergroup relations.
Practice for Second Language Learning: Don’t Throw out the Baby with the Bathwater
Authors: DeKeyser Robert
Published: January 2018

After presenting some of the main arguments against certain narrow concepts of second language practice, this article argues that a broader concept of practice, still focused on form or even forms, but with due attention to form-meaning links and with appropriate sequencing of activities to ensure declarative knowledge first, followed by its proceduralization and (at least partial) automatization, is as relevant as ever. A brief overview is given of the range of activities that fall within this concept, and recommendations are made for adaptation to students’ individual and group differences.
Critical Feedback on Written Corrective Feedback Research
Authors: Storch Neomy
Published: January 2018

Recently we have witnessed a large growth in research on written corrective feedback (WCF). However, the question posed here is: are researchers and L2 writing teachers now any wiser about the efficacy of WCF? I begin with a summary of early studies and some of their major shortcomings. I then examine more recent studies and conclude that, although many of the shortcomings of earlier research have been largely addressed, research findings are still inconclusive. I argue that currently, in the desire to conduct more robust research, the pendulum has swung too far towards experimental studies. Such studies tend to employ ‘one off’ treatments, often provided on a very restricted range of errors, and ignore the learners’ goals and attitudes to the feedback provided and to improvement in accuracy. I conclude by suggesting directions for a more meaningful and ecological valid research agenda on written corrective feedback.
The impact of computer-based feedback on students’ written work
Authors: El Ebyary Khaled , Windeatt Scott
Published: January 2018

While research in second language writing suggests that instructor feedback can have a positive influence on students’ written work, the provision of such feedback on a regular basis can be problematic, especially with larger student numbers. A number of computer programs that claim to provide both automatic computer-based holistic scores and computer-based feedback (CBF) on written work are available and therefore have the potential to deal with this issue. Criterion is one such tool that claims to be able to provide automated feedback at word, sentence, paragraph and text level, but there is still a need for more research into the practical value of providing feedback on L2 writing. Quantitative and qualitative data about feedback practice was collected from 31 instructors and 549 Egyptian trainee EFL teachers using pre-treatment questionnaires, interviews and focus groups. 24 of the trainees then received computer-based feedback using Criterion on two drafts of essays submitted on each of 4 topics. Data recorded by the software suggested a positive effect on the quality of students’ second drafts and subsequent submissions, and post-treatment questionnaires, interviews and focus groups showed a positive effect on the students’ attitudes towards feedback.
The Use of Models as a Form of Written Feedback to Secondary School Pupils of English
Authors: Martínez Esteban Noelia , Roca de Larios Julio
Published: January 2018

The present study investigated how noticing is related to composing and subsequent feedback processing in individual and collaborative EFL writing. Participants were Spanish secondary school pupils at a lowintermediate proficiency level who completed a three-stage writing task that included writing a picture-based story (Stage 1), comparing their written texts with two native-speaker models (Stage 2), and attempting subsequent revisions (Stage 3). The results indicate that the students noticed mainly lexical problems at the writing stage but could only find a few solutions to those problems in the models provided. However, the comparison with the models allowed them, especially those who wrote collaborativelly, to notice a large number of features related to the content of the pictures and the linguistic means used to express that content. They were also found to incorporate a reasonable number in subsequent revisions. A number of implications from these findings for research and pedagogy are suggested.
Future directions in feedback on second language writing: Overview and research agenda
Authors: Hyland Fiona
Published: January 2018

This article provides an overview of the contributions made to this special issue on feedback by the seven papers, examining how they reflect both the growing interest in different areas of research into feedback on writing and the continuing search by teachers for more effective feedback practices. Focusing first on the papers by Van Beuningen, Storch, Evans, Hartshorn and Allen, it discusses how these papers situate written corrective feedback research in the wider area of second language acquisition research and contribute to the debate in feedback research on research design issues. This is followed by an examination of the major findings of the four situated empirical studies by Bitchener, Ma, El-ebyary and Windeatt, and Martinez and Roca, which make up the second section. Echoing the authors of these papers, this article argues that we need more longitudinal naturalistic studies, adopting both cognitive and socio-cultural SLA frameworks to investigate the role of feedback and its impact on individual learners in more depth. Finally some pedagogic implications are discussed, including the need for feedback practices which facilitate students’ abilities to self regulate and evaluate their performance, and the need to raise teachers’ awareness of the different feedback sources and modes of delivery available to them.
The Secret to Legal Foretelling: Generic and Inter-Generic Aspects of Vagueness in Contracts, Patents and Regulations
Authors: Engberg Jan , Arinas Pellón Ismael
Published: January 2018

In this genre analysis research paper, we compare U.S. patents, contracts, and regulations on technical matters with a focus upon the relation between vagueness and communicative purposes and subpurposes of these three genres. Our main interest is the investigation of intergeneric conventions across the three genres, based on the software analysis of three corpora (one for each genre, 1 million words per corpus). The result of the investigation is that intergeneric conventions are found at the level of types of expressed linguistic vagueness, but that intergeneric conventions at the level of actual formulations are rare. The conclusion is that at this latter level the influence from the situation type underlying the individual genre is more important than the overarching legal character of the genres, when we talk about introducing explicit vagueness in the text.
Measures of speech rhythm and the role of corpus-based word frequency: a multifactorial comparison of Spanish(-English) speakers
Authors: Harris Michael J. , Gries Stefan Th.
Published: January 2018

In this study, we address various measures that have been employed to distinguish between syllable and stress- timed languages. This study differs from all previous ones by (i) exploring and comparing multiple metrics within a quantitative and multifactorial perspective and by (ii) also documenting the impact of corpus-based word frequency. We begin with the basic distinctions of speech rhythms, dealing with the differences between syllable-timed languages and stress-timed languages and several methods that have been used to attempt to distinguish between the two. We then describe how these metrics were used in the current study comparing the speech rhythms of Mexican Spanish speakers and bilingual English/Spanish speakers (speakers born to Mexican parents in California). More specifically, we evaluate how well various metrics of vowel duration variability as well as the so far understudied factor of corpus-based frequency allow to classify speakers as monolingual or bilingual. A binary logistic regression identifies several main effects and interactions. Most importantly, our results call the utility of a particular rhythm metric, the PVI, into question and indicate that corpus data in the form of lemma frequencies interact with two metrics of durational variability, suggesting that durational variability metrics should ideally be studied in conjunction with corpus-based frequency data.
A cross-language study on citation practice in PhD theses
Authors: Soler Monreal Carmen , Gil Salom Luz
Published: January 2018

Citation practice provides justification for arguments and allows a writer to indicate a rhetorical gap for her/his research and adopt a tone of authority. Claims must be supported with evidence, and writers must demonstrate an understanding of approaches and knowledge in their fields of specialisation, in order to persuade the examiners that the thesis is worthy of the award of a doctorate (Thompson, 2005b). Candidates need to keep the adequate interpersonal relationship with the immediate audience (the examiners). They have to evaluate the previous research in an area of study and to be respectful with previous claims from authorities in the disciplines. They also need to position themselves in relation to other disciplinary members and highlight their individual claims. This paper investigates contrastively how interactional resources of citation and, in particular reporting verbs, are deployed in the literature review chapters of PhD theses written in English and in Spanish.
A descriptive approach to computerised English historical corpora in the 21st century
Authors: Vázquez Nila , Esteban Segura Laura , Marqués Aguado Teresa
Published: January 2018

Historical corpora offer many potentialities for linguistic research. Thus, the present article provides an overview of the major English historical corpora compiled or being compiled both in Spain and abroad. They include different types such as tagged and parsed corpora, and their main features will be outlined. As for the organisation of the article, after the introductory section, the historical corpora created abroad will be presented. Then, those being constructed in Spain (Coruña, Las Palmas, Málaga, Salamanca, Santiago and Sevilla) will be discussed. Some final remarks and the references close the article.
A survey on approaches to the protection of personal data gathered by IoT devices
Authors: Tranter Henry
Published: January 2018

Security is always at the forefront of developing technologies. One can seldom go a week without hearing of a new data breach or hacking attempt from various groups around the world, often taking advantage of a simple flaw in a system’s architecture. The Internet of Things (IoT) is one of these developing technologies which may be at risk of such attacks. IoT devices are becoming more and more prevalent in everyday life. From keeping track of an individual’s health, to suggesting meals from items available in an individual’s fridge, these technologies are taking a much larger role in the personal lives of their users. With this in mind, how is security being considered in the development of these technologies? Are these devices that monitor individual’s personal lives just additional vectors for potential data theft? Throughout this survey, various approaches to the development of security systems concerning IoT devices in the home will be discussed, compared, and contrasted in the hope of providing an ideal solution to the problems this technology may produce.
Evidence for widespread dysregulation of circadian clock progression in human cancer
Authors: Shilts Jarrod , Chen Guanhua , Hughey Jacob J.
Published: January 2018

The ubiquitous daily rhythms in mammalian physiology are guided by progression of the circadian clock. In mice, systemic disruption of the clock can promote tumor growth. In vitro, multiple oncogenes can disrupt the clock. However, due to the difficulties of studying circadian rhythms in solid tissues in humans, whether the clock is disrupted within human tumors has remained unknown. We sought to determine the state of the circadian clock in human cancer using publicly available transcriptome data. We developed a method, called the clock correlation distance (CCD), to infer circadian clock progression in a group of samples based on the co-expression of 12 clock genes. Our method can be applied to modestly sized datasets in which samples are not labeled with time of day and coverage of the circadian cycle is incomplete. We used the method to define a signature of clock gene co-expression in healthy mouse organs, then validated the signature in healthy human tissues. By then comparing human tumor and non-tumor samples from twenty datasets of a range of cancer types, we discovered that clock gene co-expression in tumors is consistently perturbed. Subsequent analysis of data from clock gene knockouts in mice suggested that perturbed clock gene co-expression in human cancer is not caused solely by the inactivation of clock genes. Furthermore, focusing on lung cancer, we found that human lung tumors showed systematic changes in expression in a large set of genes previously inferred to be rhythmic in healthy lung. Our findings suggest that clock progression is dysregulated in many solid human cancers and that this dysregulation could have broad effects on circadian physiology within tumors. In addition, our approach opens the door to using publicly available data to infer circadian clock progression in a multitude of human phenotypes.
Nonlinear Absorption Applications of CH3NH3PbBr3 Perovskite Crystals
Authors: Wei Tzu‐Chiao , Mokkapati Sudha , Li Ting‐You , Lin Chun‐Ho , Lin Gong‐Ru , Jagadish Chennupati , He Jr‐Hau
Published: January 2018

Researchers have recently revealed that hybrid lead halide perovskites exhibit ferroelectricity, which is often associated with other physical characteristics, such as a large nonlinear optical response. In this work, the nonlinear optical properties of single crystal inorganic–organic hybrid perovskite CH3NH3PbBr3 are studied. By exciting the material with a 1044 nm laser, strong two‐photon absorption‐induced photoluminescence in the green spectral region is observed. Using the transmission open‐aperture Z‐scan technique, the values of the two‐photon absorption coefficient are observed to be 8.5 cm GW−1, which is much higher than that of standard two‐photon absorbing materials that are industrially used in nonlinear optical applications, such as lithium niobate (LiNbO3), LiTaO3, KTiOPO4, and KH2PO4. Such a strong two‐photon absorption effect in CH3NH3PbBr3 can be used to modulate the spectral and spatial profiles of laser pulses, as well as to reduce noise, and can be used to strongly control the intensity of incident light. In this study, the superior optical limiting, pulse reshaping, and stabilization properties of CH3NH3PbBr3 are demonstrated, opening new applications for perovskites in nonlinear optics.
Diarylethenes with a Narrow Singlet–Triplet Energy Gap Sensitizer: a Simple Strategy for Efficient Visible‐Light Photochromism
Authors: Zhang Zhiwei , Zhang Junji , Wu Bin , Li Xin , Chen Yi , Huang Jinhai , Zhu Liangliang , Tian He
Published: January 2018

All‐organic visible‐light photochromism is reported here via a novel strategy with narrow singlet–triplet energy gap (ΔEST) materials as a sensitizer. Taking advantage of the narrow ΔEST feature and the triplet–triplet energy transfer process, highly efficient photochromism of diarylethenes (DAEs) with both ring‐open and ring‐closure excitations shifted to visible light region is successfully achieved. Moreover, the wavelength of the visible excitation light can be easily modulated (e.g., from 405 to 470 nm) by elaborate selection of matched sensitized molecules. The “write‐and‐erase” application of this photochromic system in polymer films is further demonstrated. This strategy provides a simple and versatile selection of well‐matched DAE/sensitizer couples for visible‐light photochromism without complicated molecular design.
Ionogel Electrolytes for High‐Performance Lithium Batteries: A Review
Authors: Chen Nan , Zhang Haiqin , Li Li , Chen Renjie , Guo Shaojun
Published: January 2018

Ionic liquids (ILs) are important electrolytes for applications in electrochemical devices. An emerging trend in ILs research is their hybridization with solid matrices, named ionogels. These ionogels can not only overcome the fluidity of ILs but also exhibit high mechanical strength of the solid matrix. Therefore, they show promise for applications in building lithium batteries. In this review, various types of solid matrices for confining ILs are summarized, including nonmetallic oxides, metal oxides, IL‐tethered nanoparticles, functionalized SiO2, metal–organic frameworks, and other structural materials. The synthetic strategies for ionogels are first documented, focusing on physical confinement and covalent grafting. Then, the structure, ionic conductivity, thermal stability, and electrochemical stability of ionogels are addressed in detail. Furthermore, the authors highlight the potential applications of state‐of‐art ionogels in lithium batteries. The authors conclude this review by outlining the remaining challenges as well as personal perspectives on this hot area of research.
Miscibility–Function Relations in Organic Solar Cells: Significance of Optimal Miscibility in Relation to Percolation
Authors: Ye Long , Collins Brian A. , Jiao Xuechen , Zhao Jingbo , Yan He , Ade Harald
Published: January 2018

Polymer solar cells (PSCs) continue to be a promising low‐cost and lead‐free photovoltaic technology. Of critical importance to PSCs is understanding and manipulating the composition of the amorphous mixed phase, which is governed by the thermodynamic molecular interactions of the polymer donor and acceptor molecules and the kinetics of the casting process. This progress report clarifies and defines nomenclature relating to miscibility and its relevance and implications to PSC devices in light of new developments. Utilizing a scanning transmission X‐ray microscopy method, the temperature dependences of “molecular miscibility” in the presence of fullerene crystals, now referred to liquidus miscibility, are presented for a number of representative blends. An emphasis is placed on relating the amorphous miscibility of high‐efficiency PSC blends at a given processing temperature with their actual device performance and stability. It is shown and argued that a system with an amorphous miscibility close to percolation exhibits the most stable morphology. Furthermore, an approach is outlined to convert liquidus miscibility to an effective Flory–Huggins interaction parameter χ. Crucially, determination of temperature‐dependent amorphous miscibility paves a way to rationally optimize the stability and mixing behaviors of PSCs at actual processing and operating temperatures.
Fatal work‐related falls in the United States, 2003‐2014
Authors: Socias‐Morales Christina M. , Chaumont Menéndez Cammie K. , Marsh Suzanne M.
Published: January 2018

Background

Falls are the second leading cause of work‐related fatalities among US workers. We describe fatal work‐related falls from 2003 to 2014, including demographic, work, and injury event characteristics, and changes in rates over time.

Methods

We identified fatal falls from the Bureau of Labor Statistics (BLS), Census of Fatal Occupational Injuries and estimated rates using the BLS Current Population Survey.

Results

From 2003 to 2014, there were 8880 fatal work‐related falls, at an annual rate of 5.5 per million FTE. Rates increased with age. Occupations with the highest rates included construction/extraction (42.2 per million FTE) and installation/maintenance/repair (12.5 per million FTE). Falls to a lower level represented the majority (n = 7521, 85%) compared to falls on the same level (n = 1128, 13%).

Conclusions

Falls are a persistent source of work‐related fatalities. Fall prevention should continue to focus on regulation adherence, Prevention through Design, improving fall protection, training, fostering partnerships, and increasing communication.
Visible Light‐Induced Aerobic Oxidation of Indoles: One‐Pot Formation of 4‐Quinolones at Room Temperature
Authors: Ji Xiaochen , Li Dongdong , Wang Zhongzhen , Tan Muyun , Huang Huawen , Deng Guo‐Jun
Published: January 2018

A one‐pot synthesis of 4‐quinolones starting from indoles is disclosed. This cascade reaction involves a photocatalytic aerobic oxidation of indoles using visible light and a subsequent base‐promoted Camps cyclization. The advantages of the present protocol include the use of environmentally benign and inexpensive oxygen as the sole oxidant, easy handling at room temperature, as well as step‐ and atom‐economy.
Light‐Driven Water Splitting Mediated by Photogenerated Bromine
Authors: Sheridan Matthew V. , Wang Ying , Wang Degao , Troian‐Gautier Ludovic , Dares Christopher J. , Sherman Benjamin D. , Meyer Thomas J.
Published: January 2018

Light‐driven water splitting was achieved using a dye‐sensitized mesoporous oxide film and the oxidation of bromide (Br−) to bromine (Br2) or tribromide (Br3−). The chemical oxidant (Br2 or Br3−) is formed during illumination at the photoanode and used as a sacrificial oxidant to drive a water oxidation catalyst (WOC), here demonstrated using [Ru(bda)(pic)2], (1; pic=picoline, bda=2,2′‐bipyridine‐6,6′‐dicarboxylate). The photochemical oxidation of bromide produces a chemical oxidant with a potential of 1.09 V vs. NHE for the Br2/Br− couple or 1.05 V vs. NHE for the Br3−/Br− couple, which is sufficient to drive water oxidation at 1 (RuV/IV≈1.0 V vs. NHE at pH 5.6). At pH 5.6, using a 0.2 m acetate buffer containing 40 mm LiBr and the [Ru(4,4′‐PO3H2‐bpy)(bpy)2]2+ (RuP2+, bpy=2,2′‐bipyridine) chromophore dye on a SnO2/TiO2 core–shell electrode resulted in a photocurrent density of around 1.2 mA cm−2 under approximately 1 Sun illumination and a Faradaic efficiency upon addition of 1 of 77 % for oxygen evolution.
Ice Melting to Release Reactants in Solution Syntheses
Authors: Wei Hehe , Huang Kai , Zhang Le , Ge Binghui , Wang Dong , Lang Jialiang , Ma Jingyuan , Wang Da , Zhang Shuai , Li Qunyang , Zhang Ruoyu , Hussain Naveed , Lei Ming , Liu Li‐Min , Wu Hui
Published: January 2018

Aqueous solution syntheses are mostly based on mixing two solutions with different reactants. It is shown that freezing one solution and melting it in another solution provides a new interesting strategy to mix chemicals and to significantly change the reaction kinetics and thermodynamics. For example, a precursor solution containing a certain concentration of AgNO3 was frozen and dropped into a reductive NaBH4 solution at about 0 °C. The ultra‐slow release of reactants was successfully achieved. An ice‐melting process can be used to synthesize atomically dispersed metals, including cobalt, nickel, copper, rhodium, ruthenium, palladium, silver, osmium, iridium, platinum, and gold, which can be easily extended to other solution syntheses (such as precipitation, hydrolysis, and displacement reactions) and provide a generalized method to redesign the interphase reaction kinetics and ion diffusion in wet chemistry.
Palladium‐Catalyzed Formal Cross‐Coupling of Diaryl Ethers with Amines: Slicing the 4‐O‐5 Linkage in Lignin Models
Authors: Zeng Huiying , Cao Dawei , Qiu Zihang , Li Chao‐Jun
Published: January 2018

Lignin is the second most abundant organic matter on Earth, and is an underutilized renewable source for valuable aromatic chemicals. For future sustainable production of aromatic compounds, it is highly desirable to convert lignin into value‐added platform chemicals instead of using fossil‐based resources. Lignins are aromatic polymers linked by three types of ether bonds (α‐O‐4, β‐O‐4, and 4‐O‐5 linkages) and other C−C bonds. Among the ether bonds, the bond dissociation energy of the 4‐O‐5 linkage is the highest and the most challenging to cleave. To date, 4‐O‐5 ether linkage model compounds have been cleaved to obtain phenol, cyclohexane, cyclohexanone, and cyclohexanol. The first example of direct formal cross‐coupling of diaryl ether 4‐O‐5 linkage models with amines is reported, in which dual C(Ar)−O bond cleavages form valuable nitrogen‐containing derivatives.
An Intracellular H2O2‐Responsive AIEgen for the Peroxidase‐Mediated Selective Imaging and Inhibition of Inflammatory Cells
Authors: Cheng Yong , Dai Jun , Sun Chunli , Liu Rui , Zhai Tianyou , Lou Xiaoding , Xia Fan
Published: January 2018

Inflammatory cells have gained widespread attention because inflammatory diseases increase the risk for many types of cancer. Therefore, it is urgent and important to implement detection and treatment methods for inflammatory cells. Herein, we constructed a theranostic probe with aggregation‐induced emission (AIE) characteristics, in which tetraphenylethene (TPE) was modified with two tyrosine (Tyr) moieties. Owing to the H2O2‐dependent, enzyme‐catalyzed dityrosine formation, Tyr‐containing TPE (TT) molecules crosslink through dityrosine linkages to induce the formation of hydrophobic aggregates, activating the AIE process in inflammatory cells that contain H2O2 and overexpress myeloperoxidase. The emission turn‐on resulting from the crosslinking of TT molecules could be used to distinguish between inflammatory and normal cells. Moreover, the massive TT aggregates induced mitochondria damage and cell apoptosis. This study demonstrates that the H2O2‐responsive peroxidase‐activated AIEgen holds great promise for inflammatory‐cell selective imaging and inhibition.
Water Soluble Benzimidazole Containing Ionic Palladium(II) Complex for Rapid Microwave‐Assisted Suzuki Reaction of Aryl Chlorides
Authors: Şengül Abdurrahman , Hanhan Murat Emre
Published: January 2018

In this paper a water soluble benzimidazole – Pd complex used for Suzuki reaction under conventional heating and microwave heating. To increase the activity of complex, ionic group change with bulky TBA+ and Bmim+ groups. To determine whether the reaction is homogeneous or heterogeneous, Hg(0) poisoning tests, hot filtration tests and CS2 poisoning tests were performed.
Multi‐facet implications of PEGylated lysozyme stabilized‐silver nanoclusters loaded recombinant PTEN cargo in cancer theranostics
Authors: Arora Neha , Gavya S Lalitha , Ghosh Siddhartha S.
Published: January 2018

Amalgamation of delivery and tracking of therapeutically relevant moieties on a single platform is made possible by the application of metal nanoclusters, an innovative class of luminescent nanomaterials. Metal nanoclusters, possessing molecule‐like attributes, display extraordinary size and shape tunable properties befitting theranostic applications. Herein, we report successful assembly of therapeutically significant phosphatase protein PTEN and fluorescent lysozyme‐stabilized silver nanoclusters to accomplish delivery and tracking of the protein. Down‐regulation of PTEN perturbs the cellular networking leading to copious pathological conditions. The integration of purified recombinant PTEN with silver nanoclusters was evaluated by fluorescence spectroscopy study. A key feature of this study is the use of polyethylene glycol coating that allows fabrication of the assembly into spherical nanocomposites as characterized by transmission electron microscope along with retention of both optical functionality of the cluster and biological activity of the protein. Prior to cellular application, the functional integrity of PTEN in the composite was determined in vitro, by enzymatic assay employing para‐nitrophenylphosphate as substrate. Cellular internalization of the cargo was studied by confocal microscopy and flow cytometry analysis. The efficacy of the payload on modulation of cellular signaling was assessed on cell lines that expressed PTEN differentially. PTEN null U‐87 MG and PTEN expressing MCF7 cell lines displayed successful alteration of AKT and FAK signaling proteins culminating in cell cycle arrest and reduced wound healing capacity. A dose dependent reduction in cell proliferation of MCF7 cells was achieved. For U‐87 MG, treatment with the payload resulted in chemosensitization toward anti‐cancer drug erlotinib. Thus, PEG coated GST‐PTEN loaded silver nanoclusters serves as a comprehensive system encompassing cellular imaging and protein delivery with potential biomedical implications.
Applying interactive devices to an elementary nature science course
Authors: Wang Chian
Published: January 2018

The goal of this paper is to design and develop an interactive learning system (ILS) by integrating interactive devices into a real‐world classroom. ILS is primarily designed for elementary school students where they can have some hands‐on experiences to learn nature science such as airflow and wind. The purpose of adopting interactive devices is to increase students’ motivations and pleasures during the learning process. In order to demonstrate the learning effects of using ILS, an empirical study was conducted by comparing traditional and interactive instructional strategies. During the study, three types of measurements were used to assess the different aspects of ILS: learning achievement tests, a questionnaire about students’ experiences, and teacher interview. The results showed that ILS does have positive effects on students’ learning and we can conclude that ILS can effectively and efficiently assist in learning nature science in a real‐world classroom environment.
Analyzing Xyloglucan Endotransglycosylases by Incorporating Synthetic Oligosaccharides into Plant Cell Walls
Authors: Ruprecht Colin , Dallabernardina Pietro , Smith Peter J. , Urbanowicz Breeanna R. , Pfrengle Fabian
Published: January 2018

The plant cell wall is a cellular exoskeleton consisting predominantly of a complex polysaccharide network that defines the shape of cells. During growth, this network can be loosened through the action of xyloglucan endotransglycosylases (XETs), glycoside hydrolases that “cut and paste” xyloglucan polysaccharides through a transglycosylation process. We have analyzed cohorts of XETs in different plant species to evaluate the substrate specificities of xyloglucan acceptors by using a set of synthetic oligosaccharides obtained by automated glycan assembly. The ability of XETs to incorporate the oligosaccharides into polysaccharides printed as microarrays and into stem sections of Arabidopsis thaliana, beans, and peas was assessed. We found that single xylose substitutions are sufficient for transfer, and xylosylation of the terminal glucose residue is not required by XETs, independent of plant species. To obtain information on the potential xylosylation pattern of the natural acceptor of XETs, that is, the nonreducing end of xyloglucan, we further tested the activity of xyloglucan xylosyl transferase (XXT) 2 on the synthetic xyloglucan oligosaccharides. These data shed light on inconsistencies between previous studies towards determining the acceptor substrate specificities of XETs and have important implications for further understanding plant cell wall polysaccharide synthesis and remodeling.
NTPDase activities: possible roles on Leishmania spp infectivity and virulence
Authors: Paes‐Vieira Lisvane , Gomes‐Vieira André Luiz , Meyer‐Fernandes José Roberto
Published: January 2018

Nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes that belong to the GDA1/CD39 protein superfamily. These enzymes catalyze the hydrolysis of ATP and ADP to the monophosphate form (AMP). Biochemical characterization of the nucleotidases/NTPDases from various types of cells, including those from plants, animals, and pathogenic organisms, has revealed the existence of several isoforms with different specificities with respect to divalent cations (magnesium, calcium, manganese, and zinc) and substrates. In mammals, the NTPDases play important roles in the regulation of thrombosis and inflammation. In parasites of the genus Leishmania, the causative agents of leishmaniasis, two NTPDase isoforms, termed NTPDase‐1 and NTPDase‐2 have been described. Independently of their cellular localization, whether cell‐surface localized, secreted or targeted to other organelles, in some Leishmania species these NTPDases could be involved in parasite growth, infectivity, and virulence. Experimental evidence has suggested that the hydrolysis of ATP and ADP by parasite ecto‐nucleotidases can down‐modulate the host immune response. In this context, the present work provides an overview of recent works that show strong evidence not only of the involvement of the nucleotidases/NTPDases in Leishmania spp infectivity and virulence but also of the molecular mechanisms that lead to the success of the parasitic infection.
Structural Change of a Single Ag Nanoparticle Observed by Dark‐field Microspectroscopy
Authors: Pang Jie , Liu Hai‐Ling , Li Jian , Zhai Ting‐Ting , Wang Kang , Xia Xing‐Hua
Published: January 2018

Silver nanoparticles (AgNPs) have been widely used as photocatalysts and nanosensors. Observation of the spectroscopy of a single AgNP greatly helps us understand the catalytic characteristics and morphology change of the AgNP during reactions. In the present study, AgNPs physically adsorbed on indium tin oxide (ITO) conductive glass were electrochemically reduced and oxidized, and the plasmonic resonance Rayleigh scattering (PRRS) spectrum of an individual AgNP was observed under a dark‐field microscopy (DFM) equipped with a spectrometer. The electrochemical oxidization of the AgNP under constant potential caused a redshift of the PRRS peak for 30±5 nm. However, electrochemical reduction of the AgNP could not make the PRRS peak completely shift back to the initial position. In situ AFM and SEM characterization confirmed that very small Ag fragments (<10 nm) formed around the AgNP core during electrochemical oxidization. Results showed that dark‐field microspectroscopy could be used as a sensitive tool for estimating the morphology/structural changes of nanoparticles that can hardly be observed through the cyclic voltammograms of multiple AgNPs.
Isotropic/Anisotropic NMR Editing by Resolution‐Enhanced NMR Spectroscopy
Authors: Marcó Núria , Gil Roberto R. , Parella Teodor
Published: January 2018

Modern resolution‐enhanced NMR techniques can monitor the in situ discrimination of co‐existing isotropic and anisotropic contributions of small molecules dissolved in weakly aligning PMMA/CDCl3 media. The simultaneous sign‐sensitive determination of accurate Δδiso–aniso(1H), Δδiso–aniso(13C) and/or isotropic 1JCH and anisotropic 1TCH coupling constants (and consequently 1H‐13C residual dipolar couplings and 1H/13C residual chemical shift anisotropies) can be performed from spectral‐aliased heteronuclear single‐quantum correlation spectra.
Rapid loss of group 1 innate lymphoid cells during blood stage Plasmodium infection
Authors: Ng Susanna S , Souza‐Fonseca‐Guimaraes Fernando , Rivera Fabian de Labastida , Amante Fiona H , Kumar Rajiv , Gao Yulong , Sheel Meru , Beattie Lynette , Montes de Oca Marcela , Guillerey Camille , Edwards Chelsea L , Faleiro Rebecca J , Frame Teija , Bunn Patrick T , Vivier Eric , Godfrey Dale I , Pellicci Daniel G , Lopez J Alejandro , Andrews Katherine T , Huntington Nicholas D , Smyth Mark J , McCarthy James , Engwerda Christian R
Published: January 2018

Objectives

Innate lymphoid cells (ILCs) share many characteristics with CD4+ T cells, and group 1 ILCs share a requirement for T‐bet and the ability to produce IFNγ with T helper 1 (Th1) cells. Given this similarity, and the importance of Th1 cells for protection against intracellular protozoan parasites, we aimed to characterise the role of group 1 ILCs during Plasmodium infection.

Methods

We quantified group 1 ILCs in peripheral blood collected from subjects infected with with Plasmodium falciparum 3D7 as part of a controlled human malaria infection study, and in the liver and spleens of PcAS‐infected mice. We used genetically‐modified mouse models, as well as cell‐depletion methods in mice to characterise the role of group 1 ILCs during PcAS infection.

Results

In a controlled human malaria infection study, we found that the frequencies of circulating ILC1s and NK cells decreased as infection progressed but recovered after volunteers were treated with antiparasitic drug. A similar observation was made for liver and splenic ILC1s in P. chabaudi chabaudi AS (PcAS)‐infected mice. The decrease in mouse liver ILC1 frequencies was associated with increased apoptosis. We also identified a population of cells within the liver and spleen that expressed both ILC1 and NK cell markers, indicative of plasticity between these two cell lineages. Studies using genetic and cell‐depletion approaches indicated that group 1 ILCs have a limited role in antiparasitic immunity during PcAS infection in mice.

Discussion

Our results are consistent with a previous study indicating a limited role for natural killer (NK) cells during Plasmodium chabaudi infection in mice. Additionally, a recent study reported the redundancy of ILCs in humans with competent B and T cells. Nonetheless, our results do not rule out a role for group 1 ILCs in human malaria in endemic settings given that blood stage infection was initiated intravenously in our experimental models, and thus bypassed the liver stage of infection, which may influence the immune response during the blood stage.

Conclusion

Our results show that ILC1s are lost early during mouse and human malaria, and this observation may help to explain the limited role for these cells in controlling blood stage infection.
Regulatory T cells in renal disease
Authors: Alikhan Maliha A , Huynh Megan , Kitching A Richard , Ooi Joshua D
Published: January 2018

The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen‐specific Tregs in HLA‐mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype. Experimentally, Tregs can protect the kidney from injury in a variety of renal diseases. Mechanisms of Treg recruitment to the kidney include via the chemokine receptors CCR6 and CXCR3 and potentially, at least in innate injury TLR9. The effects of Tregs may be context dependent, with evidence for roles for immunoregulatory roles both for endogenous Tbet‐expressing Tregs and STAT‐3‐expressing Tregs in experimental glomerulonephritis. Most experimental work and some of the ongoing human trials in renal transplantation have focussed on unfractionated thymically derived Tregs (tTregs). However, induced Tregs (iTregs), type 1 regulatory T (Tr1) cells and in particular antigen‐specific Tregs also have therapeutic potential not only in renal transplantation, but also in other kidney diseases.
Endoplasmic reticulum stress in the development of multiple myeloma and drug resistance
Authors: Nikesitch Nicholas , Lee James M , Ling Silvia , Roberts Tara Laurine
Published: January 2018

Multiple myeloma (MM) is a haematological malignancy of mature antibody‐secreting plasma cells. Currently, MM is incurable, but advances in drug treatments have increased patient lifespan. One of the characteristics of MM is the excessive production of monoclonal immunoglobulin (also referred to as paraprotein). This high level of protein production induces endoplasmic reticulum (ER) stress, and proteasomal degradation of the paraprotein is required to avoid ER stress‐induced cell death. Consequently, proteasomal inhibitors such as bortezomib have been particularly effective therapies. Unfortunately development of resistance to bortezomib is common. In this review, we address how control of endoplasmic reticulum stress is important in the development of MM and how the unfolded protein response and its associated stress response pathways are involved in the development of bortezomib resistance.
Accumulation of IL‐17+ Vγ6+ γδ T cells in pregnant mice is not associated with spontaneous abortion
Authors: Polese Barbara , Gridelet Virginie , Perrier d'Hauterive Sophie , Renard Chantal , Munaut Carine , Martens Henri , Vermijlen David , King Irah L , Jacobs Nathalie , Geenen Vincent
Published: January 2018

Introduction

Pregnancy is an immune paradox. While the immune system is required for embryo implantation, placental development and progression of gestation, excessive inflammation is associated with pregnancy failure. Similarly, the cytokine IL‐17A plays an important role in defence against extracellular pathogens, but its dysregulation can lead to pathogenic inflammation and tissue damage. Although expression of IL‐17 has been reported during pregnancy, the cellular source of this cytokine and its relevance to gestation are not clear.

Objectives

Here we define the kinetics and cellular source of IL‐17A in the uterus during healthy and abortion‐prone murine pregnancy.

Methods

The CBA/J x DBA/2J abortion‐prone mating was used and compared to CBA/J x BALB/c control mating.

Results

We demonstrate that, irrespective of gestational health, the number of IL‐17‐producing cells peaks during midterm pregnancy and is largely derived from the γδ T‐cell lineage. We identify γδ T, Th17, CD8 T and NKT cells as the cellular source of IL‐17A in pregnant mice. Furthermore, we positively identify the Vγ6+ subset of uterine γδ T cells as the main producer of IL‐17A during both healthy pregnancy and abortive pregnancy.

Conclusions

To conclude, the accumulation of uterine IL‐17+ innate‐like T cells appears not to adversely impact the developing foetus. Collectively, our results show that IL‐17+ γδ T cells are present in the uterus throughout the course of normal gestation and therefore may play an important role in healthy pregnancy.
Characterisation of anti‐alpha toxin antibody levels and colonisation status after administration of an investigational human monoclonal antibody, MEDI4893, against Staphylococcus aureus alpha toxin
Authors: Ruzin Alexey , Wu Yuling , Yu Li , Yu Xiang‐Qing , Tabor David E , Mok Hoyin , Tkaczyk Christine , Jensen Kathryn , Bellamy Terramika , Roskos Lorin , Esser Mark T , Jafri Hasan S
Published: January 2018

Objectives

MEDI4893 is a novel, long‐acting human monoclonal antibody targeting Staphylococcus aureus (SA) alpha toxin (AT). This report presents the results of the exploratory analyses from a randomised phase 1 dose‐escalation study in healthy human subjects receiving single intravenous MEDI4893 doses or placebo.

Methods

Anti‐AT antibodies and AT expression were measured as described previously. Nasal swabs were analysed by culture and PCR. Data were summarised by treatment groups and visits by using SAS System Version 9.3.

Results

Subjects receiving 2250 or 5000 mg of MEDI4893 had the highest serum anti‐AT neutralising antibody (NAb) levels: approximately 180‐ to 240‐, 70‐ to 100‐ and sevenfold to 10‐fold higher than respective baseline levels at peak, 30 and 360 days, respectively. In these subjects, levels of serum anti‐AT NAbs were >3.2 International Units (IU) mL−1 for at least 211 days. In the upper respiratory tract, anti‐AT NAb levels increased with MEDI4893 dose. No apparent effect of MEDI4893 on SA nasal colonisation, hla gene sequence or AT expression was observed. Five AT variants were detected, their lytic activity was fully neutralised by MEDI4893.

Discussion

Our results indicate that (1) MEDI4893 administration at 2250 and 5000 mg would provide effective immunoprophylaxis against systemic SA disease; (2) MEDI4983 distributes to the upper respiratory tract and retains neutralising activity against AT; and (3) potential for emergence of MEDI4893 resistance is low.

Conclusion

Intravenous administration of MEDI4893 maintained levels of anti‐AT NAbs in serum and nasal mucosa that may provide effective immunoprophylaxis against SA disease and support continued clinical development of MEDI4893.
Vaccinating for natural killer cell effector functions
Authors: Wagstaffe Helen R , Mooney Jason P , Riley Eleanor M , Goodier Martin R
Published: January 2018

Vaccination has proved to be highly effective in reducing global mortality and eliminating infectious diseases. Building on this success will depend on the development of new and improved vaccines, new methods to determine efficacy and optimum dosing and new or refined adjuvant systems. NK cells are innate lymphoid cells that respond rapidly during primary infection but also have adaptive characteristics enabling them to integrate innate and acquired immune responses. NK cells are activated after vaccination against pathogens including influenza, yellow fever and tuberculosis, and their subsequent maturation, proliferation and effector function is dependent on myeloid accessory cell‐derived cytokines such as IL‐12, IL‐18 and type I interferons. Activation of antigen‐presenting cells by live attenuated or whole inactivated vaccines, or by the use of adjuvants, leads to enhanced and sustained NK cell activity, which in turn contributes to T cell recruitment and memory cell formation. This review explores the role of cytokine‐activated NK cells as vaccine‐induced effector cells and in recall responses and their potential contribution to vaccine and adjuvant development.