bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Study
Authors: Duff Patricia A.
Published: December 2021

This encyclopedia entry provides a methodological overview of case‐study research in applied linguistics, and especially in the area of second language teaching and learning. The entry begins with a definition and description of case study and references to other recent reviews of this qualitative approach to research. Examples of case‐study research are presented, together with a discussion of issues and options that arise in conducting and reporting on such research, such as ethical considerations, sampling or selection decisions, issues of generalizability, possibilities and challenges for conducting longitudinal research, and ways of analyzing and presenting data in single‐case versus multiple‐case studies. Next, the entry discusses ways of including case study in mixed methods research and cites an example from the field of study abroad research. The entry concludes with some criteria for the assessment of effective and engaging case studies.
Conversation Analysis and Second Language Acquisition: CA‐SLA
Authors: Doehler Simona Pekarek
Published: December 2021

This entry presents the conversation analytic approach to the study of second language acquisition (CA‐SLA). It briefly outlines the historical development of the field and its reconceptualization of key concepts: Learning is viewed as a socially situated practice that becomes observable through the micro‐details of social conduct; competence is defined as a locally contingent, ever adaptive ability to use semiotic resources in social interaction at the primary site of human linguistic (and more generally social and mental) functioning; language is seen as part of a complex ensemble of multimodal resources used for meaning making in interaction; and the very object of L2 learning is cast in terms of “methods” (i.e., systematic procedures), for accomplishing second language talk‐in‐interaction. The entry then provides an overview of three key lines of CA‐SLA investigation into L2 learning: (a) microgenetic studies that investigate the local‐interactional emergence of patterns of language use; (b) longitudinal work that analyzes the expansion, over time, of such patterns into new environments of use and their increased working as interaction‐organizational devices (i.e., as part of an L2 grammar‐for‐interaction); (c) longitudinal investigations of the development of L2 interactional competence that document how, over time, L2 speakers change their practices for accomplishing precise actions, such as initiating repair, offering a disagreement, or opening a storytelling. The entry concludes by identifying current developments that open avenues for future research.
Frame Analysis
Authors: Kim Youn‐Kyung
Published: December 2021

The concept of “frame” is a useful tool to explicate how people interpret and at the same time construct their interactions coherently in specific interactional situations. The concept of “frame” is traced back to Bateson, and it gets its theoretical complexity in Goffman's elaboration of “frame” and his notions of “keying” and “footing.” According to Goffman, a “frame” consists of “principles of organization which govern social events . . . and our subjective involvement in them”; that is, through frames, people identify and define social interactions, in order to participate and maintain involvement in them. Admittedly, however, the concept of frame has been used and referred to in various, but complex, ways in different disciplines, such as linguistics, anthropology, sociology, artificial intelligence, ethnography of speaking, and interactional sociolinguistics, to analyze discourses. For instance, while Bateson and Goffman explain frame as interpretational and inferential dimension (interactive/contextual frame), Tannen uses it as expectation and knowledge structure (cognitive/knowledge frame). As the concept of frame and thereby frame analysis are widely applied and adopted in various fields of study, some theoretical and methodological concerns seem to remain: for example, using a consistent definition of frame and making a clear distinction between frame and framing.
Grammar in Academic Writing
Authors: Shaw Philip M.
Published: December 2021

Academic texts use the grammar of the general language but the frequency and functions of some features are different, depending partly on the genre (such as article, textbook, student essay) and partly on the discipline (such as philosophy, history, biology, physics). Generally academic texts, and particularly research articles, in many languages are characterized by a nominal style with relatively few finite verbs. They have relatively simple clause structure but highly complex noun phrase structure. They use a narrow range of tenses and modals in specialized ways. Personal agency is often backgrounded so that disciplinary concepts and entities appear in thematized positions, for example as subjects, and this leads in English to frequent use of the passive voice. This style has been called synoptic in contrast to the “dynamic” style of conversation, with many dependent clauses and fairly simply noun phrases. As student writing becomes more mature it adopts more of these synoptic characteristics.

Academic syntax was first studied in several languages on the basis of typical texts, often research articles in the natural sciences. The rise of the concept of genre led to interest in syntactic features with particular functions in particular parts of the genre, such as pronoun use, forms of reference, and cohesion markers. More recently, use of statistical approaches drawing on corpus material has allowed more systematic quantitative descriptions of the occurrence of different features in particular (sub)genres and disciplines. It appears that the classic synoptic characteristics are most typical of quantitative research articles in the natural sciences.
Multimodal Discourse Analysis
Authors: Jones Rodney H.
Published: December 2021

Multimodal discourse analysis is an approach to discourse which focuses on how meaning is made through the use of multiple modes of communication as opposed to just language. The concept of “mode” in multimodal discourse analysis should not be confused with the concept of “modality” in grammar (which refers to the expression of possibility and obligation in language), or with the concept of “mode” in Halliday's tripartite model of context, in which mode refers to the “channel” of linguistic communication. Some scholars, while influenced by Halliday's work, developed methods of analysis that sharply diverged from both social semiotics and systemic functional analysis. Among the most notable has been the Genre and Multimodality framework (sometimes abbreviated GeM), developed chiefly by John Bateman. Another important tradition in multimodal discourse analysis has focused more on the analysis of face‐to‐face interaction, drawing its inspiration from work in sociology, anthropology, and psychiatry. More recent trends in multimodal discourse analysis are pushing scholars to consider more fully the complex ways different modes interact in communication, including how meanings change as they move across modes.
Language Program Evaluation
Authors: Chapelle Carol A.
Published: December 2021

Language program evaluation entails systematic collection of information that is useful for making judgments about the value of a program. The specific types of information gathered and the value judgments depend on the intended uses of the evaluation. In applied linguistics and social science more broadly, evaluation generally treats the whole program as the unit of analysis even though the definition of a program can vary widely. Contemporary language program evaluation practices have been motivated by both external accountability‐driven forces as well as the need for improvement and change recognized internally within some language programs. The diverse needs of audiences for program evaluations have prompted the adoption of utilization‐based evaluation, which requires examining the intended uses of evaluation outcomes early in the process of evaluation. Language program evaluation holds the potential for guiding positive change to meet the needs of an evolving society, but professional development of prospective evaluators in applied linguistics is needed to realize the potential.
Rhetorical Discourse Analysis
Authors: Andrus Jennifer
Published: December 2021

Rhetorical discourse analysis (RDA) brings together methods and theories from strands of discourse analysis (DA), classical rhetoric, and rhetorical analysis. As this entry shows, rhetoric and DA share a common object, discourse, and some of the same concerns and concepts, such as interaction, context, style, and effect. The overlapping concerns create spaces where theories and methods can be brought together to add depth and nuance to analysis. The goal of much of the scholarship that uses an RDA framework is to better understand communication in context. Discourse analysis and rhetoric come together around the common view that language, whether spoken or written, does something in addition to or beyond merely reflecting the world as it is. DA and rhetoric also share a core interest in the particulars of discourse and communication. The association between the projects of DA and rhetoric create a space of cross‐fertilization out of which a new theory of discursive action is emerging.
Teaching Culture and Intercultural Competence
Authors: Chapelle Carol A.
Published: December 2021

Which aspects of culture should be taught in a language class? Facts of geography and history, national symbols, small cultures, or ways of life, myths, and ideologies? Which kinds of culture? National, regional, or professional culture; high culture or popular culture? And whose culture should be taught? The culture of one or more target countries, or the hybrid culture of multilingual individuals who straddle various national cultures? The best responses to these questions vary across language teaching contexts where course objectives vary to meet students' needs. Culture in language teaching can be viewed from modernist or postmodernist perspectives depending on one's disciplinary and political orientation, and on whose interests are being served. These two perspectives on culture coexist today in the theory and practice of language learning and teaching and are useful for conceptualizing how and why culture is so important in language teaching.
Hydrated Deep Eutectic Electrolytes for High‐Performance Zn‐Ion Batteries Capable of Low‐Temperature Operation
Authors: Lin Xidong , Zhou Guodong , Robson Matthew J. , Yu Jing , Kwok Stephen C. T. , Ciucci Francesco
Published: December 2021

Aqueous Zn‐ion batteries (ZIBs) are a promising energy storage technology due to their intrinsic safety, eco‐friendliness, and cost‐effectiveness. However, aqueous electrolytes generally induce parasitic interfacial reactions (e.g., dendrite growth and passivation) that degrade the Zn metal anode, shortening ZIBs lifespan. This study develops a novel hydrated deep eutectic electrolyte (DEE), containing sulfolane (SL) and Zn(ClO4)2·6H2O, to prevent water‐induced deterioration. The strong coordination between SL and Zn2+ triggers the deep eutectic effect, extending the operating temperature window of the DEE. The unique water‐in‐DEE structure boosts ionic diffusion, promotes Zn2+ deposition, and reduces water reactivity, as revealed by in‐depth simulations and experiments. The developed DEE suppresses dendrite formation, allowing the Zn|DEE|Zn symmetrical cells to cycle over thousands of hours without short‐circuiting. With a polyaniline (PANI) cathode, Zn|DEE|PANI cells can cycle 2500 times with a capacity of 72 mAh g−1 at 3 A g−1 at room temperature and 500 times with 73 mAh g−1 at 0.3 A g−1 at −30 °C. The newly developed DEE significantly is a step forward for inexpensive, stable, and high‐performance ZIBs.
Cross‐Linked but Self‐Healing and Entirely Degradable Poly‐Schiff Base Metal Complex Materials for Potential Anti‐Biofouling
Authors: Yan Minglong , Guo Yuhan , Zhao Wenjie
Published: December 2021

Environmentally friendly materials with good adjustable mechanical properties, modifiability, self‐healing properties, and entirely degradable properties promote technological progress, but they fail to integrate all the attributes in a single platform. Herein, a design concept is conceived that uses the reversible bond of imine part, the metal ion–ligand coordination, and the crystallites to jointly adjust the internal structure of poly‐Schiff base (PSB) metal complexes to achieve cross‐linking, high stretchability, self‐healing, and complete degradability. The metal ion–imine ligand coordination controls the degree and distribution of the internal physical and chemical cross‐linking of such a material, presenting a very interesting and surprising feature: controllable transformation of plasticity and elasticity, high stretchability, or high strength. Due to the dynamic covalent bond of imines and metal–ligand bonding, this material shows excellent self‐healing properties at room temperature, and finally degrades into small monomers in an aqueous medium, avoiding the incurrence of microplastics. It is further expected to apply this material to create a new, biodegradable, and multifunctional anti‐biofouling material platform. It is believed that the design concept proposed here may represent a general method for preparing environmentally friendly materials, especially anti‐biofouling materials, which combine adjustable mechanical properties, self‐healing, and entirely degradable properties.
Self‐Doped TiAl Nanoparticle/AlN Metal‐Cermet Solar Selective Absorbing Films
Authors: Shi Jing , Zhao Runqiang , Ke Shenglan , Wang Wanrong , Wang Chengbing
Published: December 2021

Metal‐cermet solar selective absorber films (SSAFs) with nanoparticles embedded in dielectric matrix have been widely used in the field of solar thermal conversion. A new SSAF of TiAlN is fabricated via magnetron sputtering method. By co‐sputtering Ti and Al targets, TiAl nanoparticles are embedded in AlN matrix to form self‐doped absorber layer. And the outermost rough AlN antireflective layer further enhances the optical properties due to the optical trapping effect, as well as the heating crack extension resistance of the surface. As a result, the as‐grown SSAF displays high absorptance reaching up to 0.92 and low thermal emittance of 0.05. The selective absorption mechanism endowed by synergetic effect of intrinsic absorption and multilayers’ interference is discussed. The SSAFs optical property is stable in open‐air up to 650 °C, indicating their enormous potential for high‐temperature solar selective applications.
Spider Silk‐Inspired Artificial Fibers
Authors: Li Jiatian , Li Sitong , Huang Jiayi , Khan Abdul Qadeer , An Baigang , Zhou Xiang , Liu Zunfeng , Zhu Meifang
Published: December 2021

Spider silk is a natural polymeric fiber with high tensile strength, toughness, and has distinct thermal, optical, and biocompatible properties. The mechanical properties of spider silk are ascribed to its hierarchical structure, including primary and secondary structures of the spidroins (spider silk proteins), the nanofibril, the “core–shell”, and the “nano‐fishnet” structures. In addition, spider silk also exhibits remarkable properties regarding humidity/water response, water collection, light transmission, thermal conductance, and shape‐memory effect. This motivates researchers to prepare artificial functional fibers mimicking spider silk. In this review, the authors summarize the study of the structure and properties of natural spider silk, and the biomimetic preparation of artificial fibers from different types of molecules and polymers by taking some examples of artificial fibers exhibiting these interesting properties. In conclusion, biomimetic studies have yielded several noteworthy findings in artificial fibers with different functions, and this review aims to provide indications for biomimetic studies of functional fibers that approach and exceed the properties of natural spider silk.
Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation
Authors: Yu Yichao , Payne Christopher , Marina Nephtali , Korsak Alla , Southern Paul , García‐Prieto Ana , Christie Isabel N. , Baker Rebecca R. , Fisher Elizabeth M. C. , Wells Jack A. , Kalber Tammy L. , Pankhurst Quentin A. , Gourine Alexander V. , Lythgoe Mark F.
Published: December 2021

Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. A novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification is described here. MMS exploits the mechanosensitivity of astrocytes and triggers mechanogated Ca2+ and adenosine triphosphate (ATP) signaling by applying a magnetic field to antibody‐functionalized magnetic particles that are targeted to astrocytes. Using purpose‐built magnetic devices, the mechanosensory threshold of astrocytes is determined, a sub‐micrometer particle for effective MMS is identified, the in vivo fate of the particles is established, and cardiovascular responses are induced in rats after particles are delivered to specific brainstem astrocytes. By eliminating the need for device implantation and genetic modification, MMS is a method for controlling astroglial activity with an improved prospect for clinical application than existing technologies.
Extension services and the technical efficiency of crop‐specific farms in China
Authors: Liu Qian , Jiang Yongmu , Lagerkvist Carl‐Johan , Huang Wei
Published: December 2021

China operates the world's largest system of extension services, but knowledge about its effectiveness is limited. Using farm survey data and a stochastic meta‐frontier production function, this study investigates the impact of extension services on the technical efficiency of crop‐specific farms in China. Results reveal that extension services have a statistically significant and strongly correlated relationship with farm technical efficiency and that different sources of extension have an inconsistent impact on it. Crop‐specific farms require distinct extension provision whose content is designed to match farmers' needs, and hence a pluralistic and well‐functioning system of extension provision should be developed.
Palladium‐Catalyzed Coupling Reaction of o‐Alkenyl Chloroformylaniline with o‐Alkynylaniline: An Approach to Indolylmethyl Oxindole
Authors: Yang Fanpeng , Hu Yina , Wang Lu , Wu Miaomiao , Yuan Xiaowen , Liu Zhigang , Li Xiuhuan , Wang Zhengshen , Zheng Huaiji
Published: December 2021

A palladium‐catalyzed cascade Heck cyclization/3‐(2‐oxindolyl)methylation on intramolecular amination of o‐alkynylanilines for the synthesis of indolylmethyl oxindoles is developed. This protocol exhibits high efficiency, good functional group tolerance and scalability from easily accessible starting materials. In this transformation, chloroformylaniline was used as an oxidative reagent and o‐alkynylaniline was used as a 3‐indolyl precursor.
Plugging the Leak: Empowering Women in Organic Chemistry
Authors: Dibrell Sara E. , Holman Karli R. , Reisman Sarah E.
Published: December 2021

Held June 24–25, 2021, the third annual Empowering Women in Organic Chemistry (EWOC) conference gathered organic chemists at all stages of the career pipeline for rich professional development opportunities and a showcase of recent scientific achievements. This Meeting Review outlines the program.
Aggregation‐Induced Emission Featured Supramolecular Tubisomes for Imaging‐Guided Drug Delivery
Authors: Yang Jie , Yu Xinyang , Song Ji‐Inn , Song Qiao , Hall Stephen C. L. , Yu Guocan , Perrier Sébastien
Published: December 2021

Polymeric cylinders, a fascinating type of nanostructures with high surface area, internal volume and rigidity, have been exploited as novel drug delivery vehicles over the past decade. However, it's still an open challenge to afford cylindrical nanostructures using polymeric building blocks via traditional self‐assembly processes. Herein, we report a hierarchical self‐assembly strategy of preparing cylindrical aggregates (tubisomes) from an amphiphilic supramolecular bottlebrush polymer in which a cyclic peptide nanotube is employed as the noncovalent backbone. Additionally, an aggregation‐induced emission (AIE) effect was introduced into the tubisomes to endow them with excellent fluorescent properties. Intriguingly, by encapsulating with the anticancer drug doxorubicin (DOX), both the fluorescence of tubisome and DOX can be quenched due to the energy transfer relay (ETR) effect. The release of DOX can induce the interruption of the ETR effect and recover the silenced fluorescence, thereby permitting the in‐situ imaging of drug release. The AIE‐featured supramolecular tubisomes reported here provide an alternative approach for fabricating cylindrical polymeric nanostructures and holds great potential for imaging‐guided drug delivery.
Programmable Transient Supramolecular Chiral G‐quadruplex Hydrogels by a Chemically Fueled Non‐equilibrium Self‐Assembly Strategy
Authors: Xie Xiao‐Qiao , Zhang Yunfei , Liang Yujia , Wang Mengke , Cui Yihan , Li Jingjing , Liu Chun‐Sen
Published: December 2021

The temporal and spatial control of natural systems has aroused great interest for the creation of synthetic mimics. By using boronic ester based dynamic covalent chemistry and coupling it with an internal pH feedback system, we have developed a new chemically fueled reaction network for non‐equilibrium supramolecular chiral G‐quadruplex hydrogels with programmable lifetimes from minutes, to hours, to days, as well as high transparency and conductivity, excellent injectability, and rapid self‐healing properties. The system can be controlled by the kinetically controlled in situ formation and dissociation of dynamic boronic ester bonds between the cis‐diol of guanosine (G) and 5‐fluorobenzoxaborole (B) in the presence of chemical fuels (KOH and 1,3‐propanesultone), thereby leading to a precipitate‐solution‐gel‐precipitate cycle under non‐equilibrium conditions. A combined experimental‐computational approach showed the underlying mechanism of the non‐equilibrium self‐assembly involves aggregation and disaggregation of right‐handed helical G‐quadruplex superstructures. The proposed dynamic boronic ester‐based non‐equilibrium self‐assembly strategy offers a new option to design next‐generation adaptive and interactive smart materials.
Sintering graded foamed beads: Compressive properties
Authors: Errichiello Fabrizio , Cammarano Aniello , Di Maio Ernesto , Nicolais Luigi
Published: December 2021

Designing the foam structures in terms of density and morphology gives the chance to tune their mechanical and functional properties to the specific application. Nowadays, this design has been leveled up by the introduction of graded foams which are characterized by spatially nonuniform densities and/or morphologies. Graded foams have proved superior compared to uniform one in numerous examples and loading conditions but in pure compressive loading, where properties such as the Young's modulus of graded foams are always inferior to uniform ones. When using sintered beads foams, macroscopic pure compression may induce local bending on the single bead, which can be exploited to induce stiffening. This thesis was investigated on both polystyrene and thermoplastic polyurethane samples made by foamed beads sintered in a cylindrical mold. The response to compressive tests of graded foams made by sintering beads having nonuniform cells structures was compared to the uniform counterparts. The results evidenced that, at same average density, foams had up to a 30% ca. of increase of the Young's modulus when the beads are characterized by a denser outer layer.
Contribution of Interleukin‐4–Induced Epithelial Cell Senescence to Glandular Fibrosis in IgG4‐Related Sialadenitis
Authors: Min Sai‐Nan , Zhu Meng‐Qi , Mao Xiang‐Di , Li Wei , Wei Tai , Mei Mei , Zhang Yan , Wu Li‐Ling , Yu Guang‐Yan , Cong Xin
Published: December 2021

Objective

IgG4‐related sialadenitis (IgG4‐RS) is a chronic fibroinflammatory disease characterized by glandular fibrosis and hyposalivation. This study was undertaken to explore the role of cellular senescence in the pathogenesis of IgG4‐RS–related fibrosis.

Methods

The expression of senescence markers and proinflammatory cytokines in the submandibular glands (SMGs) of IgG4‐RS patients (n = 18) and controls (n = 14) was determined by proteomics, real‐time polymerase chain reaction, Western blotting, and immunohistochemistry. After interleukin‐4 (IL‐4) treatment, high‐throughput RNA sequencing was performed to identify the differentially expressed genes in SMG‐C6 cells. A glandular fibrosis model was established by the intraglandular injection of IL‐4 into mouse SMGs (n = 8 per group).

Results

Salivary acinar and ductal epithelial cells underwent senescence in IgG4‐RS patients, as indicated by the elevated activity of senescence‐associated β‐galactosidase, lipofuscin accumulation, enhanced expression of senescence markers (p53 and p16INK4A), and up‐regulation of senescence‐associated secretory phenotype factors. Moreover, there was a significant increase in IL‐4 levels in SMGs from IgG4‐RS patients (P < 0.01), which positively correlated with p16INK4A expression and the fibrosis score. Incubation with IL‐4 exacerbated salivary epithelial cell senescence by increasing the expression of p16INK4A through the reactive oxygen species (ROS)/p38 MAPK pathway. Supernatant collected from IL‐4–induced senescent SMG‐C6 cells enhanced fibroblast activation and matrix protein production (P < 0.05). Furthermore, injecting mice with IL‐4 promoted fibrosis and senescence phenotypes in SMGs in vivo.

Conclusion

The cellular senescence induced by IL‐4 through the ROS/p38 MAPK‐p16INK4A pathway promotes fibrogenesis in IgG4‐RS. Our data suggest that cellular senescence could serve as a novel therapeutic target for treating IgG4‐RS.
Diastolic Dysfunction in Systemic Sclerosis: Risk Factors and Impact on Mortality
Authors: Hinze Alicia M. , Perin Jamie , Woods Adrianne , Hummers Laura K. , Wigley Fredrick M. , Mukherjee Monica , Shah Ami A.
Published: December 2021

Objective

To determine the independent risk factors for diastolic dysfunction (DD) in patients with systemic sclerosis (SSc) and to evaluate the impact of DD on mortality.

Methods

SSc patients enrolled in the Johns Hopkins Scleroderma Center Cohort between November 1, 2006 and November 1, 2017 with ≥1 analyzable 2‐dimensional (2‐D) echocardiogram in our system were included (n = 806). DD risk factors and SSc disease characteristics were prospectively obtained, and the presence or absence of DD was determined using the most recent 2‐D echocardiogram. Logistic regression models examined associations between clinical risk factors and DD, and Cox proportional hazards models were used to assess survival.

Results

DD was present in 18.6% of participants. The majority of participants were female (84%) with a median age of 58.4 years (interquartile range 48.8–68.1). Older age (odds ratio [OR] 1.12 [95% confidence interval (95% CI) 1.09–1.15], P < 0.001), coronary artery disease (OR 3.69 [95% CI 1.52–8.97], P = 0.004), obesity (OR 4.74 [95% CI 2.57–8.74], P < 0.001), longer SSc disease duration (OR 1.04 [95% CI 1.01–1.06], P = 0.004), diffusing capacity for carbon monoxide ≤60% of predicted (OR 2.41 [95% CI 1.40–4.16], P = 0.002), and history of scleroderma renal crisis (OR 3.18 [95% CI 1.12–9.07], P = 0.031) were all independently associated with an increased risk of DD. Anti–Scl‐70 positivity (OR 0.49 [95% CI 0.26–0.93], P = 0.03) and severe gastrointestinal disease (OR 0.48 [95% CI 0.30–0.79], P = 0.004) were associated with a reduced risk of DD. The presence of DD was independently associated with an increase in the risk of mortality (hazard ratio 1.69 [95% CI 1.07–2.68], P = 0.027).

Conclusion

DD is independently associated with an increased risk of mortality in patients with SSc. Potentially modifiable risk factors, including coronary artery disease and obesity, should be addressed in patients with SSc to reduce mortality risk.
Enabling biocatalysis in high‐concentration organic cosolvent by enzyme gate engineering
Authors: Cheng Feng , Li Ming‐You , Wei Dian‐Ju , Zhang Xiao‐Jian , Jia Dong‐Xu , Liu Zhi‐Qiang , Zheng Yu‐Guo
Published: December 2021

Biocatalysis in high‐concentration organic solvents (OSs) offers many advantages, but realizing this process remains a huge challenge. An R‐selective ω‐amine transaminase variant (AcATAM2) exhibited high activity toward 50 g/L pro‐sitagliptin ketone 1‐[1‐piperidinyl]‐4‐[2,4,5‐trifluorophenyl]‐1,3‐butanedione (PTfpB). However, AcATAM2 displayed unsatisfactory organic–cosolvent resistance against high‐concentration dimethyl sulfoxide (DMSO), which is required to enhance the solubility of the hydrophobic substrate PTfpB. Located in the substrate‐binding tunnel, enzyme gates are structural elements that undergo reversible conformational transitions, thus affecting the accessibility of the binding pocket to solvent molecules. Depending on the conformation of the enzyme gates, one can define an open or closed conformation on which the enzyme activity in OSs may depend. To enhance the DMSO resistance of AcATAM2, we identified the beneficial residues at the “enzyme gate” region via computational analysis, alanine scanning, and site‐saturation mutagenesis. Two beneficial variants, namely, AcATAM2F56D and AcATAM2F56V, not only displayed improved enzyme activity but also exhibited enhanced DMSO resistance (the half‐life value increased from 25.71 to 42.49 h under 60% DMSO). Molecular dynamic simulations revealed that the increase in DMSO resistance was mainly caused by the decrease in the number of DMSO molecules in the substrate‐binding pocket. Moreover, in the kilogram‐scale experiment, the conversion of 80 g/L substrate was increased from 50% (AcATAM2) to 85% (M2F56D in 40% DMSO) with a high e.e. of >99% within 24 h.
Anti‐fibrosis attributes: UHPLC‐MS/MS‐based pharmacokinetics profiling of a novel autotaxin inhibitor with excellent in vivo efficacy in rat
Authors: Wang Hongjin , Long Tengfei , Zhang Hao , Li Meng , Sun Qi , Zhai Xin , Sun Lixin
Published: December 2021

3,4‐Difluorobenzyl(1‐ethyl‐5‐(4‐((4‐hydroxypiperidin‐1‐yl)‐methyl)thiazol‐2‐yl)‐1H‐indol‐3‐yl)carbamate (NAI59), a small molecule with outstanding therapeutic effectiveness to anti‐pulmonary fibrosis, was developed as an autotaxin inhibitor candidate compound. To evaluate the pharmacokinetics and plasma protein binding of NAI59, a UPLC–MS/MS method was developed to quantify NAI59 in plasma and phosphate‐buffered saline. The calibration curve linearity ranged from 9.95 to 1990.00 ng/mL in plasma. The accuracy was −6.8 to 5.9%, and the intra‐ and inter‐day precision was within 15%. The matrix effect and recovery, as well as dilution integrity, were within the criteria. The chromatographic and mass spectrometric conditions were also feasible to determine phosphate‐buffered saline samples, and it has been proved that this method exhibits good precision and accuracy in the range of 9.95–497.50 ng/mL in phosphate‐buffered saline. This study is the first to determine the pharmacokinetics, absolute bioavailability, and plasma protein binding of NAI59 in rats using this established method. Therefore, the pharmacokinetic profiles of NAI59 showed a dose‐dependent relationship after oral administration, and the absolute bioavailability in rats was 6.3%. In addition, the results of protein binding showed that the combining capacity of NAI59 with plasma protein attained 90% and increased with the increase in drug concentration.
Semi‐rational Engineering of a Promiscuous Fatty Acid Hydratase for Alteration of Regioselectivity
Authors: Zhang Yan , Breum Niels Mikkel Dyrby , Schubert Sune , Hashemi Negin , Kyhnau Rikke , Knauf Marius Sandholt , Mathialakan Masuthan , Takeuchi Michiki , Kishino Shigenobu , Ogawa Jun , Kristensen Peter , Guo Zheng , Eser Bekir Engin
Published: December 2021

Fatty acid hydratases (FAHs) catalyze regio‐ and stereo‐selective hydration of unsaturated fatty acids to produce hydroxy fatty acids. Fatty acid hydratase‐1 (FA‐HY1) from Lactobacillus Acidophilus is the most promiscuous and regiodiverse FAH identified so far. Here, we engineered binding site residues of FA‐HY1 (S393, S395, S218 and P380) by semi‐rational protein engineering to alter regioselectivity. Although it was not possible to obtain a completely new type of regioselectivity with our mutant libraries, a significant shift of regioselectivity was observed towards cis‐5, cis‐8, cis‐11, cis‐14, cis‐17‐eicosapentaenoic acid (EPA). We identified mutants (S393/S395 mutants) with excellent regioselectivity, generating a single hydroxy fatty acid product from EPA (15‐OH product), which is advantageous from application perspective. This result is impressive given that wild‐type FA‐HY1 produces a mixture of 12‐OH and 15‐OH products at 63 : 37 ratio (12‐OH : 15‐OH). Moreover, our results indicate that native FA‐HY1 is at its limit in terms of promiscuity and regiospecificity, thus it may not be possible to diversify its product portfolio with active site engineering. This behavior of FA‐HY1 is unlike its orthologue, fatty acid hydratase‐2 (FA‐HY2; 58 % sequence identity to FA‐HY1), which has been shown earlier to exhibit significant promiscuity and regioselectivity changes by a few active site mutations. Our reverse engineering from FA‐HY1 to FA‐HY2 further demonstrates this conclusion.
Pt3Fe Nanoparticles Triggered High Catalytic Performance for Oxygen Reduction Reaction in Both Alkaline and Acidic Media
Authors: Zhang Shuaihui , Jiang Kaiyue , Jiang Haitao , Zhu Jinhui , Ji Huiping , Lu Chenbao , Zhang Longhai , Li Jin , Chen Zhenying , Ke Changchun , Zhuang Xiaodong
Published: December 2021

Pt‐based nanomaterials are now the most reliable catalysts for oxygen reduction reaction (ORR). However, the low atomic utilization efficiency and poor stability severely limit their widespread application. Herein, a facile molten salt approach for synthesizing N‐doped porous carbon embedded with Pt3Fe intermetallic nanoparticles is presented. The Pt loading of the as‐prepared materials is as low at 5.91 wt. %, while exhibiting a half‐wave potential of 0.85 V and diffusion limiting current density of −5.68 mA cm−2 in alkaline condition, which is superior to commercial Pt/C (0.83 V, −5.48 mA cm−2). As cathode for Zn‐air battery, the power density and specific capacity up to 130.0 mW cm−2 and 833 mAh g−1, respectively, are outperforming Pt/C batteries (85.8 mW cm−2, 632 mAh g−1). The theoretical calculations identify the origin of activity on Pt3Fe; the Pt3Fe (111) plane exhibits more positive activity than (200) plane.
Parahydrogen‐Induced Polarization in Hydrogenation Reactions Mediated by a Metal‐Free Catalyst
Authors: Zakharov Danila O. , Chernichenko Konstantin , Sorochkina Kristina , Yang Shengjun , Telkki Ville‐Veikko , Repo Timo , Zhivonitko Vladimir V.
Published: December 2021

We report nuclear spin hyperpolarization of various alkenes achieved in alkyne hydrogenations with parahydrogen over a metal‐free hydroborane catalyst (HCAT). Being an intramolecular frustrated Lewis pair aminoborane, HCAT utilizes a non‐pairwise mechanism of H2 transfer to alkynes that normally prevents parahydrogen‐induced polarization (PHIP) from being observed. Nevertheless, the specific spin dynamics in catalytic intermediates leads to the hyperpolarization of predominantly one hydrogen in alkene. PHIP enabled the detection of important HCAT‐alkyne‐H2 intermediates through substantial 1H, 11B and 15N signal enhancement and allowed advanced characterization of the catalytic process.
Synthesis, Structure, and Dynamics of Chiral Eight‐Membered Cyclic Molecules with Thienylene and Cyclopropylene Units Alternately Connected
Authors: Miura Tomoya , Ishihara Yumi , Nakamuro Takayuki , Moritani Shunsuke , Nagata Yuuya , Murakami Masahiro
Published: December 2021

A rhodium(II)‐catalyzed asymmetric cyclooligomerization of bifunctional monomers possessing triazolyl and vinyl groups at 2,3‐ and 3,4‐positions on the thiophene ring is studied. Structurally interesting cyclic dimers in which thienylene and cyclopropylene units are alternately connected are obtained as the major components. The eight‐membered rings in the center are non‐planar and adopt a tub‐shaped conformation. We also observe the phenomenon of racemization caused by a tub‐to‐tub ring‐flipping, the activation energy of which is determined as 108 kJ mol−1 by electronic circular dichroism spectra measurement.
Large‐scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma
Authors: Suzuki Masaru , Cole John J. , Konno Satoshi , Makita Hironi , Kimura Hiroki , Nishimura Masaharu , Maciewicz Rose A.
Published: December 2021

Background

Chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases.

Methods

The plasma proteome was evaluated using an aptamer‐based affinity proteomics platform (SOMAscan®), representing 1238 proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics.

Results

Subjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under‐explored.

Conclusion

This investigational study evaluating the plasma proteome in clinically‐phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups.
Lignin‐First Monomers to Catechol: Rational Cleavage of C−O and C−C Bonds over Zeolites
Authors: Wu Xian , Liao Yuhe , Bomon Jeroen , Tian Guilong , Bai Shao‐Tao , Van Aelst Korneel , Zhang Qiang , Vermandel Walter , Wambacq Ben , Maes Bert U. W. , Yu Jihong , Sels Bert F.
Published: December 2021

A catalytic route is developed to synthesize bio‐renewable catechol from softwood‐derived lignin‐first monomers. This process concept consists of two steps: 1) O‐demethylation of 4‐n‐propylguaiacol (4‐PG) over acidic beta zeolites in hot pressurized liquid water delivering 4‐n‐propylcatechol (4‐PC); 2) gas‐phase C‐dealkylation of 4‐PC providing catechol and propylene over acidic ZSM‐5 zeolites in the presence of water. With large pore sized beta‐19 zeolite as catalyst, 4‐PC is formed with more than 93 % selectivity at nearly full conversion of 4‐PG. The acid‐catalyzed C‐dealkylation over ZSM‐5 zeolite with medium pore size gives a catechol yield of 75 %. Overall, around 70 % catechol yield is obtained from pure 4‐PG, or 56 % when starting from crude 4‐PG monomers obtained from softwood by lignin‐first RCF biorefinery. The selective cleavage of functional groups from biobased platform molecules through a green and sustainable process highlights the potential to shift feedstock from fossil oil to biomass, providing drop ins for the chemicals industry.
Electrochemical Activation of C−C Bonds through Mediated Hydrogen Atom Transfer Reactions
Authors: Yan Bing , Shi Changxia , Beckham Gregg T. , Chen Eugene Y.‐X. , Román‐Leshkov Yuriy
Published: December 2021

Activating inert sp3–sp3 carbon‐carbon (C−C) bonds remains a major bottleneck in the chemical upcycling of recalcitrant polyolefin waste. In this study, redox mediators are used to activate the inert C−C bonds. Specifically, N‐hydroxyphthalimide (NHPI) is used as the redox mediator, which is oxidized to phthalimide‐N‐oxyl (PINO) radical to initiate hydrogen atom transfer (HAT) reactions with benzylic C−H bonds. The resulting carbon radical is readily captured by molecular oxygen to form a peroxide that decomposes into oxygenated C−C bond‐scission fragments. This indirect approach reduces the oxidation potential by >1.2 V compared to the direct oxidation of the substrate. Studies with model compounds reveal that the selectivity of C−C bond cleavage increases with decreasing C−C bond dissociation energy. With NHPI‐mediated oxidation, oligomeric styrene (OS510; Mn=510 Da) and polystyrene (PS; Mn≈10 000 Da) are converted into oxygenated monomers, dimers, and oligomers.
Selective Electrosynthesis of 2,5‐Diformylfuran in a Continuous‐Flow System
Authors: Zhang Yuchi , Li Wenjing , Cao Yucai , Chen Ming , Li Wenqian , Zai Jiantao , Iqbal Asma , Qi Rongrong , Qian Xuefeng
Published: December 2021

The gram‐scale selective oxidation of biomass‐based chemicals, in particular 5‐hydroxymethylfurfural (HMF), into value‐added 2,5‐diformylfuran (DFF) has a high application potential but suffers from high cost, low selectivity, and harsh reaction conditions. Besides, the electrooxidation strategy requires the usage of expensive electrodes and struggles with low selectivity and efficiency, which restricts its further scaled‐up application. In this regard, a continuous‐flow system was developed through redox mediator I−/I2 for the efficient synthesis of DFF, which could accelerate the mass transfer of I− (I2) to aqueous (organic) phase and avoid over‐oxidation to achieve high selectivity. After the solvent system, iodine concentration, and reaction time were optimized, highly efficient DFF synthesis (selectivity >99 %) could be achieved in the electrochemical flow system using inexpensive graphite felt (GF) as electrode. Moreover, selective HMF oxidation was paired with the hydrogen evolution reaction with increased efficiency after using in‐situ‐loaded GF‐CoS2/CoS and GF‐Pt electrodes. As a result, the required energy to achieve the gram‐scale synthesis of DFF was significantly reduced, demonstrating outstanding potential for large‐scale production of the target product.
‘Scare the Bear’ with these tips for workplace bullying
Authors: Hodges Dawn Z.
Published: December 2021

Not long ago, I had lunch with a former colleague. She was recounting an incident that happened at her vacation home in Florida when she was cooking a rather fragrant meal. She looked out on the patio to see a black bear tear through the screen and come look in her back door. She called animal control. They said they don't relocate the bears because “they don't do well in the wild.” So, what was she to do? “Scare the bear,” they told her.
Share secrets for success for students with ADD/ADHD
Authors: Hope Joan
Published: December 2021

Students with attention deficit hyperactivity disorder should not treat their ADHD lightly, said Shanna Pearson, Founder and President of Expert ADHD Coaching. These students have double the college drop‐out rate as students without ADHD, she added. But ADHD can be a superpower if used correctly. “Your brain will never run out of energy, and that's a gift,” she tells students.
DOJ/ED issue joint guidance on student self‐harm during COVID‐19
Authors: Charmatz Marc
Published: December 2021

The U.S. Department of Justice and the U.S. Department of Education have issued Supporting and Protecting the Rights of Students at Risk of Self‐Harm in the Era of COVID‐19, joint guidance that notes that “The COVID‐19 pandemic has caused more than a year of loss, isolation, and uncertainty for many people, including students, across the country. For some students, these stressors may have caused a mental health disability to worsen. Others may be experiencing mental health disabilities for the first time. In some situations, there may be a risk that a student will engage in self‐harm or consider suicide.”
Comparative development of limb musculature in phylogenetically and ecologically divergent lizards
Authors: Diaz Raul E. , Taylor‐Diaz Elizabeth A. , Trainor Paul A. , Diogo Rui , Molnar Julia L.
Published: December 2021

Background

Squamate reptiles (lizards, snakes, and amphisbaenians) exhibit incredible diversity in their locomotion, behavior, morphology, and ecological breadth. Although they often are used as models of locomotor diversity, surprisingly little attention has been given to muscle development in squamate reptiles. In fact, the most detailed examination was conducted almost 80 years ago and solely focused on the proximal limb regions. Herein, we present forelimb and hindlimb muscle morphogenesis data for three lizard species with different locomotion and feeding strategies: the desert grassland whiptail lizard, the central bearded dragon, and the veiled chameleon. This study fills critical gaps in our understanding of muscle morphogenesis in squamate reptiles and presents a comparative and temporospatial analysis of muscle development.

Results

Our results reveal a conserved pattern of early muscle development among lizards with different adult morphologies and ecologies. The variations that exist are concentrated in distal regions, particularly the specialized autopodia of chameleons, where differentiation of muscles associated with the digits is delayed.

Conclusions

The chameleon autopod provides an example of major evolutionary modifications to the skeleton with only minor disruption of the conserved order and pattern of limb muscle development. This robustness of muscle patterning facilitates the evolution of extreme yet functional phenotypes.
Practice makes perfect: Commentary on Burnette et al. (2021)
Authors: De Young Kyle P. , Kambanis Paraskevi Evelyna
Published: December 2021

Underrepresented identities have been overlooked in the development of measures assessing eating disorders; therefore, limited normative data exist for these identities. To address this, Burnette et al. sought to provide Eating Disorder Examination‐Questionnaire and Eating Attitudes Test‐26 norms for transgender adults using Amazon's MTurk. However, they were unable to achieve this goal due to what they perceived as high rates of invalid responses. Instead, they provided recommendations for conducting MTurk research. However, little or no evidence supports the validity of several recommendations, partly because their study was not designed to derive or validate recommendations. By their own admission, their strategies failed to address what they identified as the central problem. We express concern about Burnette et al.'s recommendations because (a) the recommendations are built on assumptions about the problem that may not be true; and (b) the recommendations are not provided within the context of limitations of self‐report/online data collection writ large. We detail these concerns and propose that strategies for mitigating inattentive/invalid responding be subjected to validation prior to being recommended to prevent the implementation of procedures that result in the exclusion of the target population, individuals who we historically, and perhaps still, unjustly exclude from research.