bluuebunny/crossref_metadata_2025 huggingface dataset:
THE TRANSFORMATION OF R.A. KOSASIH'S MAHABHARATA WAYANG COMICS DESIGN: COMPARISON OF THE 1955 VERSION WITH THE 1975 VERSION
Authors: Gunawan Iwan
Published: May 2020

Mahabharata was an epic Hindu story that has been adapted to comics for so many times, by many comic artists. R.A. Kosasih, was one that was known for his mastery in creatingWayang Comics, and Mahabharata was his best creation. He created two versions of Mahabharata comics. The first was in 1955, published by Melodi and the second in 1975, by Maranatha. The storylines were basically the same, but there were differences not only in formats or spelling system, but in the visual narratives. The pictures in Maranatha version were designed in a more up dated style in comics. In the Maranatha version, R.A. Kosasih adjusted his drawing style like younger artist at that time. The angles of the scene drawn were more dynamic and variated. The scene itself expressed an adjustment to the lifestyles at that time. Consciously or unconsciously, R.A. Kosasih practised what a popular artist usually did: to always adapt to changes of. Even in his 56th of age he still succeeded to create another popular work.
The Generative Lexicon
Authors: Pustejovsky James
Published: May 2020

The first formally elaborated theory of a generative approach to word meaning, The Generative Lexicon lays the foundation for an implemented computational treatment of word meaning that connects explicitly to a compositional semantics.

The Generative Lexicon presents a novel and exciting theory of lexical semantics that addresses the problem of the "multiplicity of word meaning"; that is, how we are able to give an infinite number of senses to words with finite means. The first formally elaborated theory of a generative approach to word meaning, it lays the foundation for an implemented computational treatment of word meaning that connects explicitly to a compositional semantics.

In contrast to the static view of word meaning (where each word is characterized by a predetermined number of word senses) that imposes a tremendous bottleneck on the performance capability of any natural language processing system, Pustejovsky proposes that the lexicon becomes an active—and central—component in the linguistic description. The essence of his theory is that the lexicon functions generatively, first by providing a rich and expressive vocabulary for characterizing lexical information; then, by developing a framework for manipulating fine-grained distinctions in word descriptions; and finally, by formalizing a set of mechanisms for specialized composition of aspects of such descriptions of words, as they occur in context, extended and novel senses are generated.

The subjects covered include semantics of nominals (figure/ground nominals, relational nominals, and other event nominals); the semantics of causation (in particular, how causation is lexicalized in language, including causative/unaccusatives, aspectual predicates, experiencer predicates, and modal causatives); how semantic types constrain syntactic expression (such as the behavior of type shifting and type coercion operations); a formal treatment of event semantics with subevents); and a general treatment of the problem of polysemy.

Language, Speech, and Communication series

Bradford Books imprint
Race in the Making
Authors: Hirschfeld Lawrence A.
Published: May 2020

Race in the Making provides a new understanding of how people conceptualize social categories and shows why this knowledge is so readily recruited to create and maintain systems of unequal power.

Hirschfeld argues that knowledge of race is not derived from observations of physical difference nor does it develop in the same way as knowledge of other social categories. Instead, his central claim is that racial thinking is the product of a special-purpose cognitive competence for understanding and representing human kinds. The book also challenges the conventional wisdom that race is purely a social construction by demonstrating that a common set of abstract principles underlies all systems of racial thinking, whatever other historical and cultural specificities may be associated with them.

Starting from the commonplace observation that race is a category of both power and the mind, Race in the Making directly tackles this issue. Through a sustained exploration of continuity and change in the child's notion of race and across historical variations in the race concept, Hirschfeld shows that a singular commonsense theory about human kinds constrains the way racial thinking changes, whether in historical time or during childhood.

After surveying the literature on the development of a cultural psychology of race, Hirschfeld presents original studies that examine children's (and occasionally adults') representations of race. He sketches how a jointly cultural and psychological approach to race might proceed, showing how this approach yields new insights into the emergence and elaboration of racial thinking.

Bradford Books imprint
Sketches of Thought
Authors: Goel Vinod
Published: May 2020

Vinod Goel argues that the cognitive computational conception of the world requires our thought processes to be precise, rigid, discrete, and unambiguous; yet there are dense, ambiguous, and amorphous symbol systems, like sketching, painting, and poetry, found in the arts and much of everyday discourse that have an important, nontrivial place in cognition.

Much of the cognitive lies beyond articulate, discursive thought, beyond the reach of current computational notions. In Sketches of Thought, Vinod Goel argues that the cognitive computational conception of the world requires our thought processes to be precise, rigid, discrete, and unambiguous; yet there are dense, ambiguous, and amorphous symbol systems, like sketching, painting, and poetry, found in the arts and much of everyday discourse that have an important, nontrivial place in cognition.

Goel maintains that while on occasion our thoughts do conform to the current computational theory of mind, they often are—indeed must be—vague, fluid, ambiguous, and amorphous. He argues that if cognitive science takes the classical computational story seriously, it must deny or ignore these processes, or at least relegate them to the realm of the nonmental.

As a cognitive scientist with a design background, Goel is in a unique position to challenge cognitive science on its own territory. He introduces design problem solving as a domain of cognition that illustrates these inarticulate, nondiscursive thought processes at work through the symbol system of sketching. He argues not that such thoughts must remain noncomputational but that our current notions of computation and representation are not rich enough to capture them.

Along the way, Goel makes a number of significant and controversial interim points. He shows that there is a principled distinction between design and nondesign problems, that there are standard stages in the solution of design problems, that these stages correlate with the use of different types of external symbol systems; that these symbol systems are usefully individuated in Nelson Goodman's syntactic and semantic terms, and that different cognitive processes are facilitated by different types of symbol systems.

Bradford Books imprint
The mitochondrial genome ofAcrobeloides varius(Cephalobomorpha) confirms non-monophyly of Tylenchina (Nematoda)
Authors: Kim Taeho , Lee Yucheol , Kil Hyun-Jong , Park Joong-Ki
Published: May 2020

The infraorder Cephalobomorpha is a diverse and ecologically important nematode group found in almost all terrestrial environments. In a recent nematode classification system based on SSU rDNA, Cephalobomorpha was classified within the suborder Tylenchina with Panagrolaimomorpha, Tylenchomorpha and Drilonematomorpha. However, phylogenetic relationships among species within Tylenchina are not always consistent, and the phylogenetic position of Cephalobomorpha is still uncertain. In this study, in order to examine phylogenetic relationships of Cephalobomorpha with other nematode groups, we determined the complete mitochondrial genome sequence ofAcrobeloides varius, the first sequenced representative of Cephalobomorpha, and used this sequence for phylogenetic analyses along with 101 other nematode species. Phylogenetic analyses using amino acid and nucleotide sequence data of 12 protein-coding genes strongly support a sister relationship between the two cephalobomorpha speciesA. variusandAcrobeles complexus(represented by a partial mt genome sequence).In this mitochondrial genome phylogeny, Cephalobomorpha was sister to all chromadorean species (excludingPlectus acuminatusof Plectida) and separated from Panagrolaimomorpha and Tylenchomorpha, rendering Tylenchina non-monophyletic. Mitochondrial gene order among Tylenchina species is not conserved, and gene clusters shared betweenA. variusandA.complexusare very limited. Results from phylogenetic analysis and gene order comparison confirms Tylenchina is not monophyletic. To better understand phylogenetic relationships among Tylenchina members, additional mitochondrial genome information is needed from underrepresented taxa representing Panagrolaimomorpha and Cephalobomorpha.
Emission from Uyo Main Refuse Dumpsite and Potential Impact on Health
Authors: Nta S. A. , Ayotamuno M. J. , Igoni A. H. , Okparanma R. N.
Published: May 2020

This paper presents potential impact on health of emission from landfill site on Uyo village road, Uyo local government area of Akwa Ibom State, Nigeria. Three sampling points were assessed for particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), sulphur dioxide (SO2), carbon monoxide (CO), hydrogen sulphide H2S, ammonia (NH3), total volatile organic carbon (TVOC) and hydrogen cyanide (HCN) using highly sensitive digital portable meters. The data obtained were expressed in terms of an air quality index. Air quality index indicates that the ambient air can be described as unhealthy for sensitive groups for NO2, unhealthy for SO2 and PM2.5 and moderate for CO, respectively. H2S, NH3, TVOC, HCN, PM10 were not indicated in USEPA air quality standards. It recommended that stringent and proper landfill emissions management together with appropriate burning of wastes should be considered in the study area to ease the risks associated with these pollutants on public health.
Numerical Modeling of Biological Oxygen Demand (BOD5) Load in Apa Mmini Stream
Authors: Daniel Ogbebor , Ify Nwaogazie L. , Yusuf Momoh O. L. , Onyedikachukwu Ndekwu B.
Published: May 2020

Aim: The study aimed at utilizing finite element modeling approach for extrapolation of BOD5 along the longitudinal length of the stream.

Study Design: The linear element method was used for analyzing the Biological Oxygen Demand (BOD) transport along the longitudinal length of the stream using the Advective dispersive equation (ADE) as the governing equation.  In this study, it was assumed that dispersion was negligible.

Methodology: The BOD5 transport within the stream was modeled using finite element approach. The equation for the stream water pollution modeling was used and the descriptive variables are described as; D is the dispersion coefficient, C is the unknown or state variable (concentration of pollutant or dissolved salt), V is the velocity or convection parameter, k is the applied source or sink and t is the time coordinates.

Results: Prediction results of the finite element model showed that BOD5 decreased downstream from the point of slaughterhouse effluent expulsion. It was observed that both the observed and predicted values of BOD5 correlated strongly with a correlation coefficient of 0.9686. The decrease in BOD5 downstream proves that there is a low rate of re-aeration of the stream; hence the effluent still exceeds the FMEnv recommended standard of 50 mg/l as it travels downstream along the stream profile. The prediction discloses that the river is highly polluted for long stretch of the watercourse, thus implying that selected system of treatment method must be put in place.

Conclusion: Finite element modeling approach was utilized for the extrapolation of BOD5 in Apa Mmini stream. The outcomes of the simulation showed that the Apa Mmini stream is highly polluted with BOD5 of 111.8 mg/l which is far above the FMEnv recommended standard of 50 mg/l.
Design and Practice of Chemistry Teachers' Workshop Supported by Virtual Reality Technology
Authors: Xu Beibei , Xu Suyi , Jaspe Christsam Joy S. , Xu Ying
Published: May 2020

Introducing virtual reality technology into the chemistry teachers' workshops can motivate teachers immersion and participation in workshop, and promote the research effect of the workshops, which is beneficial the professional development of teachers. Based on the characteristic of chemistry subject, this paper focus on the scheme and effect of introduction virtual reality technology into teachers' workshop. A comparative experiment is used to discuss the practical effect of teachers' workshop. By designing a framework strategy, virtual reality technology is introduced in teachers' workshop, the experimental group (51) and the control group (58) was established for comparative study. Adopt the method of quantitative analysis to evaluate the quantitative and qualitative data of knowledge sharing. Particularly, by utilizing the Kappa value estimated the consistency of table that measures the quality of knowledge sharing. The experimental group is superior to the control group in terms of login frequency, average online time and quality of knowledge sharing content. It logged in 2.5 times a day for an average of 1.7 hours, however, the control group with an average of 0.9 hours. The experimental group average 1.38 posts were greater than the control group with average 0.78 posts which issued by each teacher. Then, the average score of "theme" in the experimental group was higher than the experimental group about 1.7344 point, in the quality of knowledge sharing. And, the average score of contribution in the experimental group was higher than the control group too. The experimental results show that the introduction of virtual reality technology in the workshop can effectively improve the enthusiasm and participation of teachers, the teachers' research effect in this designed workshop also was increased significantly.
Synthetic Triterpenoid CDDO-Me Inhibits Proliferation, Migration, and Invasion in GBM8401 and GBM8901
Authors: Chang Chih-Hui , Tsai Hung-Pei , Kuo Shih-Hsun , Loh Joon-Khim , Lin Chien-Ju , Lin Chih-Lung , Kwan Aij-Lie
Published: May 2020

Objectives:

We determined the anticancer potency of CDDO-Me in glioblastoma cell lines and the underlying mechanisms in vitro.

CDDO-Me is a synthetic triterpenoid with more potent anticancer and cancer preventive actions compared with the original triterpenoid CDDO.

Methods:

Two glioblastoma cell lines, GBM8401 and GBM8901, were utilized to test the effect of CDDO-Me on cell viability, cell migration, and cell invasion using the MTT, wound healing, and transwell migration assays, respectively. Additionally, Western blotting was used to determine the protein expression levels of N-cadherin, cyclin D1, and vascular endothelial growth factor.

Results:

At nanomolar concentrations, CDDO-Me inhibited proliferation, migration, and invasion in both cell lines. In addition, CDDO-Me exhibited a dose-dependent downregulation in the protein levels of N-cadherin, cyclin D1, and vascular endothelial growth factor in GBM8401 and GBM8901 cells.

Conclusions:

CDDO-Me exhibited anticancer effects at low nanomolar concentrations and should be considered as a potential chemotherapeutic agent for glioblastoma.
Characterization of PHGDH expression in bladder cancer: potential targeting therapy with gemcitabine/cisplatin and the contribution of promoter DNA hypomethylation
Authors: Yoshino Hirofumi , Enokida Hideki , Osako Yoichi , Nohata Nijiro , Yonemori Masaya , Sugita Satoshi , Kuroshima Kazuki , Tsuruda Masafumi , Tatarano Shuichi , Nakagawa Masayuki
Published: May 2020

d‐3‐Phosphoglycerate dehydrogenase (PHGDH) conducts an important step in the synthesis of serine. Importantly, the PHGDH gene is often amplified in certain cancers. Our previous studies revealed that PHGDH gene amplification was associated with poor overall survival in clear cell renal cell carcinoma (ccRCC) and that metabolic reprogramming of serine synthesis through PHGDH recruitment allowed ccRCC cells to survive in unfavorable environments. There have been no investigations of the role of PHGDH expression in bladder cancer (BC). In this investigation, we examined the clinical importance of PHDGH in BC. Furthermore, we asked whether PHGDH expression could be exploited for BC therapy. Finally, we investigated the regulatory mechanisms that modulated the expression of PHGDH. Using data from The Cancer Genome Atlas, we found that patients with high‐grade BC had significantly higher PHGDH expression levels than did those with low‐grade BC. In addition, patients with high PHGDH expression did not survive as long as those with low expression. PHGDH downregulation by si‐RNAs or an inhibitor in BC cell lines significantly inhibited proliferative ability and induced apoptosis. Furthermore, combined treatment using a PHGDH inhibitor and gemcitabine/cisplatin achieved synergistic tumor suppression compared to use of a single agent both in vitro as well as in vivo. Mechanistic analyses of PHGDH regulation showed that PHGDH expression might be associated with DNA copy number and hypomethylation in BC. These findings suggest novel therapeutic strategies could be used in BC. Finally, our data enhance our understanding of the role of PHGDH in BC.
Human fibronectin extra domain B as a biomarker for targeted therapy in cancer
Authors: Lieverse Relinde I. Y. , Marcus Damiënne , van der Wiel Alexander M. A. , Van Limbergen Evert J. , Theys Jan , Yaromina Ala , Lambin Philippe , Dubois Ludwig J.
Published: May 2020

The extracellular matrix protein fibronectin contains a domain that is rarely found in healthy adults and is almost exclusively expressed by newly formed blood vessels in tumours, particularly in solid tumours, different types of lymphoma and some leukaemias. This domain, called the extra domain B (ED‐B), thus has broad therapeutic potential. The antibody L19 has been developed to specifically target ED‐B and has shown therapeutic potential when combined with cytokines, such as IL‐2. In this review article, we discuss the preclinical research and clinical trials that highlight the potential of ED‐B targeting for the imaging and treatment of various types of cancer. ED‐B‐centred studies also highlight how proper patient stratification is of utmost importance for the successful implementation of novel antibody‐based targeted therapies.
Cardiac troponin and tropomyosin bind to F‐actin cooperatively, as revealed by fluorescence microscopy
Authors: Solís Christopher , Robinson John M.
Published: May 2020

In cardiac muscle, binding of troponin (Tn) and tropomyosin (Tpm) to filamentous (F)‐actin forms thin filaments capable of Ca2+‐dependent regulation of contraction. Tpm binds to F‐actin in a head‐to‐tail fashion, while Tn stabilizes these linkages. Valuable structural and functional information has come from biochemical, X‐ray, and electron microscopy data. However, the use of fluorescence microscopy to study thin filament assembly remains relatively underdeveloped. Here, triple fluorescent labeling of Tn, Tpm, and F‐actin allowed us to track thin filament assembly by fluorescence microscopy. It is shown here that Tn and Tpm molecules self‐organize on actin filaments and give rise to decorated and undecorated regions. Binding curves based on colocalization of Tn and Tpm on F‐actin exhibit cooperative binding with a dissociation constant Kd of ~ 0.5 µm that is independent of the Ca2+ concentration. Binding isotherms based on the intensity profile of fluorescently labeled Tn and Tpm on F‐actin show that binding of Tn is less cooperative relative to Tpm. Computational modeling of Tn‐Tpm binding to F‐actin suggests two equilibrium steps involving the binding of an initial Tn‐Tpm unit (nucleation) and subsequent recruitment of adjacent Tn‐Tpm units (elongation) that stabilize the assembly. The results presented here highlight the utility of employing fluorescence microscopy to study supramolecular protein assemblies.
Higher Disability in Women Than Men Scheduled for Total Knee Arthroplasty for Degenerative Osteoarthritis: A Cross‐Sectional Analysis From India
Authors: Devasenapathy Niveditha , Malhotra Rajesh , Mittal Kanchan , Garg Bhavuk , Kumar Vijay , Zodpey Sanjay , Dogra Hardik , Maddison Ralph , Belavy Daniel L.
Published: May 2020

Objective

Higher level impairments and activity limitation among those scheduled for total knee arthroplasty (TKA) is known. Sex differences in participation restriction which is the final domain of disablement pathway is not known. No data from developing countries exist on sex differences in disability levels at the time of TKA.

Methods

In a cross‐sectional analysis of 240 patients (188 women; 72 men) scheduled for TKA, impairment (pain, symptoms, quadricep muscle strength, and knee range of motion [ROM]), activity limitation (self‐reported and objective performance‐based measurements), and participation restriction were compared. Multivariable regression analyses were used to adjust for key sociodemographic and clinical characteristics. Associations between impairments and participation restriction were analyzed.

Results

Compared with men, women were more likely to have higher levels of impairment (knee injury and osteoarthritis outcome pain score adjusted mean difference [aMD]: −6.9 [95% confidence interval {CI} −13.7 to −0.18]; flexion ROM of less than 100° adjusted odds ratio: 5.7 [95% CI 1.6‐20.3]; and 36% lower muscle strength [95% CI 24%‐49%]) and lower objectively measured functional ability (walking speed aMD: −0.12 m/s [95% CI −0.23 to −0.02]; stair climbing time aMD: 9.5 s [95% CI 1.5‐17.5]). Participation restriction was higher in women compared with men. Of the impairment measures (pain, ROM, and muscle strength), pain contributed to participation restriction in both sexes.

Conclusion

This study demonstrated higher levels of disability in women than in men at the time of TKA. Effect of pain on participation restriction was higher compared with muscle strength and ROM. Evidence of delay in decision‐making to undergo TKA and reasons for delay need to be studied specifically in the context of lower middle–income countries.
Probiotic Use and Psoriatic Arthritis Disease Activity
Authors: Grinnell Madison , Ogdie Alexis , Wipfler Kristin , Michaud Kaleb
Published: May 2020

Objective

Probiotics have been hypothesized to mediate inflammation through gut microbiome modulation. Spondyloarthropathies have subclinical gut inflammation associated with inflammatory disease that may benefit from probiotic use. We aimed to evaluate associations between probiotic use and patient‐reported outcomes in patients with psoriatic arthritis (PsA).

Methods

Using FORWARD, The National Databank for Rheumatic Diseases, we examined probiotic use among patients with PsA and rheumatoid arthritis (RA), a comparator in which gut inflammation is less clearly related to pathogenesis. Patient‐reported outcome measures such as pain and physical function were compared for probiotic users and nonusers among patients with PsA and RA. Patients were propensity score–matched for taking a probiotic by demographics and nonmedication supplements.

Results

More patients have reported probiotic use over the past decade, with less than 1% reporting use in 2008 and approximately 7% in 2018. Probiotic users are more likely to be white women with higher education, income, and supplement use. Following propensity score matching, probiotic users with PsA had significantly lower Short Form 36 Physical Component Summary (SF‐36 PCS) scores and higher pain scores than nonusers with PsA (33.11 ± 11.50 vs. 40.82 ± 11.03; P = 0.04 and 4.78 ± 3.09 vs. 3.00 ± 2.58; P = 0.03). There were no significant differences in Patient Activity Scale II, Health Assessment Questionnaire II, SF‐36 PCS, and Short Form 36 Mental Component Summary scores or pain among users with PsA before and after probiotic initiation.

Conclusion

We found increasing probiotic use in patients with PsA and important differences between users and nonusers. After accounting for these differences, we found no statistical difference in health outcomes after probiotic use.
ROS and GSH Dual‐Responsive GEM Prodrug Micelles for ROS‐Triggered Fluorescence Turn on Bioimaging and Cancer Therapy
Authors: Su Xin , Zhuang Weihua , Yu Tao , He Haiyang , Ma Boxuan , Chen Liang , Yang Li , Li Gaocan , Wang Yunbing
Published: May 2020

Nanocarriers with minimal drug leakage in blood and sufficient drug release at tumor sites are essential for tumor targeted drug delivery and bioimaging. Herein, a reactive oxygen species (ROS) and glutathione (GSH) dual‐responsive aggregation‐induced quenching (ACQ) prodrug micelle system is developed based on PMPC‐P (Se‐co‐RB)‐P (SS‐GEM) copolymer to avoid drug leakage and specifically locate the tumor via a ROS‐triggered fluorescence turn on manner. Selenium (Se) group is designed to respond to the ROS environment of tumor so as to turn on the fluorescence of Rhodamine B (RB) and Gemcitabine (GEM) is conjugated to the copolymer via a disulfide bond. These GEM prodrug micelles exhibit small particle size of 166.3 nm with uniformed size distribution, a very weak fluorescence emission, and minimal drug release with only 3.33% drug release under physiological conditions after 48 h. However, ROS (0.1% H2O2) and GSH (10 × 10−3 m) could synergistically promote disassembly of the micellar structure which causes accelerated drug release up to around 91.57% after 48 h. These prodrug micelles exhibit great in vitro and in vivo antitumor ability with minimal side effects. This novel drug delivery system provides new possibilities for designing stimuli‐responsive nanocarriers for tumor therapy and bioimaging.
Visible‐Light‐Induced Radical Defluoroborylation of Trifluoromethyl Alkenes: An Access to gem‐Difluoroallylboranes
Authors: Chen Guojun , Wang Liling , Liu Xiaozu , Liu Peijun
Published: May 2020

A photoredox‐catalyzed defluoroborylation of trifluoromethyl alkenes with N‐heterocyclic carbene boranes is described for the synthesis of gem‐difluoroallylboranes. This protocol exhibits a broad substrate scope and good functional group compatibility, which enables the late‐stage functionalization of structurally complex compounds. Further transformations of the defluoroborylation products to valuable CF2‐containing molecules are also demonstrated.

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An Efficient Approach to Functionalized Indoles from λ3‐Iodanes via Acyloxylation and Acyl Transfer
Authors: Jeyakannu Palaniraja , Chandru Senadi Gopal , Chiang Chun‐Hsien , Kumar Dhandabani Ganesh , Chang Yu‐Ching , Wang Jeh‐Jeng
Published: May 2020

Versatile role of λ3‐iodanes has been identified between the reaction of hydroquinone and β‐enaminones for the synthesis of 5‐acyloxy‐4‐hydroxy indoles. The reaction is proposed to proceed through an intermolecular C−C bond formation, intramolecular cyclization, acyloxylation and 1,4‐acyl migration. The important features of this work include various acyloxylation from λ3‐iodanes and broad functional group tolerance to deliver 34 examples in moderate to good yields.

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Hydrophosphination of Activated Alkenes by a Cobalt(I) Pincer Complex
Authors: Nolla‐Saltiel Roberto , Geer Ana M. , Taylor Laurence J. , Churchill Olivia , Davies E. Stephen , Lewis William , Blake Alexander J. , Kays Deborah L.
Published: May 2020

Herein we report the synthesis of three heteroleptic first‐row transition metal(II) complexes containing carbazolido NNN pincer ligands and conversion to the corresponding metal(I)‐carbonyl complexes via a reductive carbonylation route. These complexes are precatalysts for the hydrophosphination of activated alkenes, affording a cobalt‐catalysed hydrophosphination process that solely and selectively yields the β addition (anti‐Markovnikov) product. The scope of this transformation has been investigated using a variety of activated alkenes. Isolation and characterisation of substrate‐coordinated intermediates reveal available coordination sites, which provide insight into the proposed catalytic cycle.

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MAPT haplotype–stratified GWAS reveals differential association for AD risk variants
Authors: Strickland Samantha L. , Reddy Joseph S. , Allen Mariet , N'songo Aurelie , Burgess Jeremy D. , Corda Morgane M. , Ballard Travis , Wang Xue , Carrasquillo Minerva M. , Biernacka Joanna M. , Jenkins Gregory D. , Mukherjee Shubhabrata , Boehme Kevin , Crane Paul , Kauwe John S. , Ertekin‐Taner Nilüfer ,   Alzheimer's Disease Genetics Consortium
Published: May 2020

Introduction

MAPT H1 haplotype is implicated as a risk factor for neurodegenerative diseases including Alzheimer's disease (AD).

Methods

Using Alzheimer's Disease Genetics Consortium (ADGC) genome‐wide association study (GWAS) data (n = 18,841), we conducted a MAPT H1/H2 haplotype–stratified association to discover MAPT haplotype–specific AD risk loci.

Results

We identified 11 loci—5 in H2‐non‐carriers and 6 in H2‐carriers—although none of the MAPT haplotype–specific associations achieved genome‐wide significance. The most significant H2 non‐carrier–specific association was with a NECTIN2 intronic (P = 1.33E‐07) variant, and that for H2 carriers was near NKX6‐1 (P = 1.99E‐06). The GABRG2 locus had the strongest epistasis with MAPT H1/H2 variant rs8070723 (P = 3.91E‐06). Eight of the 12 genes at these loci had transcriptome‐wide significant differential expression in AD versus control temporal cortex (q < 0.05). Six genes were members of the brain transcriptional co‐expression network implicated in “synaptic transmission” (P = 9.85E‐59), which is also enriched for neuronal genes (P = 1.0E‐164), including MAPT.

Discussion

This stratified GWAS identified loci that may confer AD risk in a MAPT haplotype–specific manner. This approach may preferentially enrich for neuronal genes implicated in synaptic transmission.
A New Glycogen Storage Disease Caused by a Dominant PYGM Mutation
Authors: Echaniz‐Laguna Andoni , Lornage Xavière , Laforêt Pascal , Orngreen Mette C. , Edelweiss Evelina , Brochier Guy , Bui Mai T. , Silva‐Rojas Roberto , Birck Catherine , Lannes Béatrice , Romero Norma B. , Vissing John , Laporte Jocelyn , Böhm Johann
Published: May 2020

Objective

Glycogen storage diseases (GSDs) are severe human disorders resulting from abnormal glucose metabolism, and all previously described GSDs segregate as autosomal recessive or X‐linked traits. In this study, we aimed to molecularly characterize the first family with a dominant GSD.

Methods

We describe a dominant GSD family with 13 affected members presenting with adult‐onset muscle weakness, and we provide clinical, metabolic, histological, and ultrastructural data. We performed exome sequencing to uncover the causative gene, and functional experiments in the cell model and on recombinant proteins to investigate the pathogenic effect of the identified mutation.

Results

We identified a heterozygous missense mutation in PYGM segregating with the disease in the family. PYGM codes for myophosphorylase, the enzyme catalyzing the initial step of glycogen breakdown. Enzymatic tests revealed that the PYGM mutation impairs the AMP‐independent myophosphorylase activity, whereas the AMP‐dependent activity was preserved. Further functional investigations demonstrated an altered conformation and aggregation of mutant myophosphorylase, and the concurrent accumulation of the intermediate filament desmin in the myofibers of the patients.

Interpretation

Overall, this study describes the first example of a dominant glycogen storage disease in humans, and elucidates the underlying pathomechanisms by deciphering the sequence of events from the PYGM mutation to the accumulation of glycogen in the muscle fibers. ANN NEUROL 2020;88:274–282.
Distal γ‐C(sp3)−H Olefination of Ketone Derivatives and Free Carboxylic Acids
Authors: Park Han Seul , Fan Zhoulong , Zhu Ru‐Yi , Yu Jin‐Quan
Published: May 2020

Reported herein is the distal γ‐C(sp3)−H olefination of ketone derivatives and free carboxylic acids. Fine tuning of a previously reported imino‐acid directing group and using the ligand combination of a mono‐N‐protected amino acid (MPAA) and an electron‐deficient 2‐pyridone were critical for the γ‐C(sp3)−H olefination of ketone substrates. In addition, MPAAs enabled the γ‐C(sp3)−H olefination of free carboxylic acids to form diverse six‐membered lactones. Besides alkyl carboxylic acids, benzylic C(sp3)−H bonds also could be functionalized to form 3,4‐dihydroisocoumarin structures in a single step from 2‐methyl benzoic acid derivatives. The utility of these protocols was demonstrated in large scale reactions and diversification of the γ‐C(sp3)−H olefinated products.
A Conjugated Polymer Containing Arylazopyrazole Units in the Side Chains for Field‐Effect Transistors Optically Tunable by Near Infra‐Red Light
Authors: Tian Jianwu , Liu Zitong , Jiang Wenlin , Shi Dandan , Chen Liangliang , Zhang Xisha , Zhang Guanxin , Di Chong‐an , Zhang Deqing
Published: May 2020

Optically tunable field‐effect transistors (FETs) with near infra‐red (NIR) light show promising applications in various areas. Now, arylazopyrazole groups are incorporated in the side chains of a semiconducting donor–acceptor (D‐A) polymer. The cis–trans interconversion of the arylazopyrazole can be controlled by 980 nm and 808 nm NIR light irradiation, by utilizing NaYF4:Yb,Tm upconversion nanoparticles and the photothermal effect of conjugated D‐A polymers, respectively. This reversible transformation affects the interchain packing of the polymer thin film, which in turn reversibly tunes the semiconducting properties of the FETs by the successive 980 nm and 808 nm light irradiation. The resultant FETs display fast response to NIR light, good resistance to photofatigue, and stability in storage for up to 120 days. These unique features will be useful in future memory and bioelectronic wearable devices.
Stereoselective Synthesis of 1,1′‐Disaccharides by Organoboron Catalysis
Authors: Izumi Sanae , Kobayashi Yusuke , Takemoto Yoshiji
Published: May 2020

The highly stereoselective synthesis of 1,1′‐disaccharides was achieved by using 1,2‐dihydroxyglycosyl acceptors and glycosyl donors in the presence of a tricyclic borinic acid catalyst. In this reaction, the complexation of the diols and the catalyst is crucial for the activation of glycosyl donors, as well as for the 1,2‐cis‐configuration of the products. The anomeric stereochemistry of the glycosyl donor depends on the employed glycosyl donor. Applications of the produced 1,1′‐disaccharides are also described.
ACQ‐to‐AIE Transformation: Tuning Molecular Packing by Regioisomerization for Two‐Photon NIR Bioimaging
Authors: Li Yuanyuan , Liu Shunjie , Ni Huwei , Zhang Haoke , Zhang Hequn , Chuah Clarence , Ma Chao , Wong Kam Sing , Lam Jacky W. Y. , Kwok Ryan T. K. , Qian Jun , Lu Xuefeng , Tang Ben Zhong
Published: May 2020

The traditional design strategies for highly bright solid‐state luminescent materials rely on weakening the intermolecular π–π interactions, which may limit diversity when developing new materials. Herein, we propose a strategy of tuning the molecular packing mode by regioisomerization to regulate the solid‐state fluorescence. TBP‐e‐TPA with a molecular rotor in the end position of a planar core adopts a long‐range cofacial packing mode, which in the solid state is almost non‐emissive. By shifting molecular rotors to the bay position, the resultant TBP‐b‐TPA possesses a discrete cross packing mode, giving a quantum yield of 15.6±0.2 %. These results demonstrate the relationship between the solid‐state fluorescence efficiency and the molecule's packing mode. Thanks to the good photophysical properties, TBP‐b‐TPA nanoparticles were used for two‐photon deep brain imaging. This molecular design philosophy provides a new way of designing highly bright solid‐state fluorophores.
Triplet Acceptors with a D‐A Structure and Twisted Conformation for Efficient Organic Solar Cells
Authors: Qin Linqing , Liu Xingzheng , Zhang Xin , Yu Jianwei , Yang Lei , Zhao Fenggui , Huang Miaofei , Wang Kangwei , Wu Xiaoxi , Li Yuhao , Chen Hao , Wang Kai , Xia Jianlong , Lu Xinhui , Gao Feng , Yi Yuanping , Huang Hui
Published: May 2020

Triplet acceptors have been developed to construct high‐performance organic solar cells (OSCs) as the long lifetime and diffusion range of triplet excitons may dissociate into free charges instead of net recombination when the energy levels of the lowest triplet state (T1) are close to those of charge‐transfer states (3CT). The current triplet acceptors were designed by introducing heavy atoms to enhance the intersystem crossing, limiting their applications. Herein, two twisted acceptors without heavy atoms, analogues of Y6, constructed with large π‐conjugated core and D‐A structure, were confirmed to be triplet materials, leading to high‐performance OSCs. The mechanism of triplet excitons were investigated to show that the twisted and D‐A structures result in large spin–orbit coupling (SOC) and small energy gap between the singlet and triplet states, and thus efficient intersystem crossing. Moreover, the energy level of T1 is close to 3CT, facilitating the split of triplet exciton to free charges.
Spatiotemporal Delivery of CRISPR/Cas9 Genome Editing Machinery Using Stimuli‐Responsive Vehicles
Authors: Cai Weiqi , Luo Tianli , Mao Lanqun , Wang Ming
Published: May 2020

Recent innovations in genome editing have enabled the precise manipulation of the genetic information of mammalians, and benefitted the development of next‐generation gene therapy. Despite these advances, several barriers to the clinical translation of genome editing remain, including the intracellular delivery of genome editing machinery, and the risk of off‐target editing effect. Here, we review the recent advance of spatiotemporal delivery of CRISPR/Cas9 genome editing machinery, which is composed of programmable Cas9 nuclease and a single‐guide RNA (sgRNA) using stimuli‐responsive nanoparticles. We discuss the specific chemistries that have been used for controlled Cas9/sgRNA delivery and intracellular release in the presence of endogenous or external signals. These methodologies can leverage biological signals found locally within disease cells, or exogenous signals administrated with spatiotemporal control, through which an improved genome editing could be achieved. We also discuss the future in exploiting these approaches for fundamental biomedical applications and therapeutic genome editing.
Designing 3D‐MoS2Sponge as Excellent Cocatalysts in Advanced Oxidation Processes for Pollutant Control
Authors: Zhu Lingli , Ji Jiahui , Liu Jun , Mine Shinya , Matsuoka Masaya , Zhang Jinlong , Xing Mingyang
Published: May 2020

3D‐MoS2can adsorb organic molecules and provide multidimensional electron transport pathways, implying a potential application for environment remediation. Here, we study the degradation of aromatic organics in advanced oxidation processes (AOPs) by a 3D‐MoS2sponge loaded with MoS2nanospheres and graphene oxide (GO). Exposed Mo4+active sites on 3D‐MoS2can significantly improve the concentration and stability of Fe2+in AOPs and keep the Fe3+/Fe2+in a stable dynamic cycle, thus effectively promoting the activation of H2O2/peroxymonosulfate (PMS). The degradation rate of organic pollutants in the 3D‐MoS2system is about 50 times higher than without cocatalyst. After a 140 L pilot‐scale experiment, it still maintains high efficiency and stable AOPs activity. After 16 days of continuous reaction, the 3D‐MoS2achieves a degradation rate of 120 mg L−1antibiotic wastewater up to 97.87 %. The operating cost of treating a ton of wastewater is only US$ 0.33, suggesting huge industrial applications.
Visible Light‐Induced Decarboxylative Alkylation of Heterocyclic Aromatics with Carboxylic Acids via Anthocyanin as a Photocatalyst
Authors: Guo Rui , Zuo Minghui , Tian Qinye , Hou Chuanfu , Sun Shouneng , Guo Weihao , Wu Hongfeng , Chu Wenyi , Sun Zhizhong
Published: May 2020

A visible light‐induced decarboxylative alkylation of heterocyclic aromatics with aliphatic carboxylic acids was developed by using anthocyanins as a photocatalyst under mild conditions. A series of alkylated heterocyclic compounds were obtained in moderate to good yields by using the metal‐free decarboxylative coupling reaction under blue light. This strategy uses cheap and readily available carboxylic acids as alkylation reagents with good functional group tolerance and environmental friendliness. It is worth noting that this is the first time that anthocyanin has been used to catalyze the Minisci‐type C−H alkylation. The mechanism of decarboxylation alkylation was studied by capturing the adduct of alkyl radical and hydroquinone, thus confirming a radical mechanism. This protocol provides an alternative visible light‐induced decarboxylative alkylation for the functionalization of heterocyclic aromatics.
Techno‐economic analysis of inulooligosaccharides, protein, and biofuel co‐production from Jerusalem artichoke tubers: A biorefinery approach
Authors: Bedzo Oscar K. K. , Mandegari Mohsen , Görgens Johann F.
Published: May 2020

Jerusalem artichoke (JA) is a crop with excellent potential for application in biorefineries. It can resist drought, pests, and diseases and can thrive well in marginal lands with little fertilizer application. The JA tubers contain considerable quantities of inulin, which is suitable for the production of inulooligosaccharides (IOS), as a high‐value prebiotic, dietary fiber. In this study, five JA tuber biorefinery scenarios were simulated in Aspen Plus® and further evaluated by techno‐economic and sensitivity analyses. Production of IOS, proteins and animal feed was studied in scenarios A and C, applying various biorefinery configurations. Scenario B explored the option of producing only IOS and the sale of residues as animal feed. Scenarios D and E investigated the economic potential of biofuel generation from residues after IOS and protein production by generation of biogas and ethanol respectively, from residues. Based on the chosen economic indicators, scenario B resulted in the lowest minimum selling price (MSP) of 3.91 US$ kg−1 (market price 5.0 US$ kg−1) with correspondingly reduced total capital investment (TCI) and total operating cost (TOC) per mass unit produced of IOS of 18.91 and 2.59 US$ kg−1 respectively, compared with other studied scenarios. Considering the set production scale, it is more profitable when the residues are sold as animal feed instead of being converted into biofuel, due to the capital‐intensive nature of the biofuel production processes. The coproduction of protein had a negative impact on the economics of the process as the associated capital and operating expenditure outweighed the associated revenue. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd
Virtual reality tumor navigated robotic radical prostatectomy by using three‐dimensional reconstructed multiparametric prostate MRI and 68Ga‐PSMA PET/CT images: A useful tool to guide the robotic surgery?
Authors: Canda Abdullah Erdem , Aksoy Sertac Fatih , Altinmakas Emre , Koseoglu Ersin , Falay Okan , Kordan Yakup , Çil Barbaros , Balbay Mevlana Derya , Esen Tarik
Published: May 2020

Objectives

To evaluate the use and benefits of tumor navigation during performing robotic assisted radical prostatectomy (RARP).

Patients and Methods

Borders of the visible tumor(s) was/were and surrounding structures marked on multiparametric prostate magnetic resonance imaging (mpMRI) and 68Ga‐labeled prostate‐specific membrane antigen ligand using positron emission computed tomography (Ga68 PSMA‐PET/CT). Three dimensional (3D) reconstruction of the images were done that were transferred to virtual reality (VR) headsets and Da Vinci surgical robot via TilePro. Images were used as a guide during RARP procedures in five cases. Indocyanine green (ICG) guided pelvic lymph node dissection (n = 2) and Martini Klinik Neurosafe technique (n = 2) were also applied.

Results

Mean patient age was 60.6 ± 3.7 years (range, 56‐66). All VR models were finalized with the agreement of radiologist, urologist, nuclear physician, and engineer. Surgeon examined images before the surgery. All VR models were found very useful particularly in pT3 diseases. Pathological stages included pT2N0 (n = 1), pT3aN0 (n = 1), pT3aN1 (n = 2), and pT3bN1 (n = 1). Positive surgical margins (SMs) occurred in two patients with extensive disease (pT3aN1 and pT3bN1) and tumor occupied 30% and 50% of the prostate volumes. Mean estimated blood loss was 150 ± 86.6 cc (range, 100‐300). Mean follow‐up was 3.4 ± 1.7 months (range, 2‐6). No complication occurred during perioperative (0‐30 days) and postoperative (30‐90 days) periods in any patient.

Conclusions

3D reconstructed VR models by using mpMRI and Ga68 PSMA‐PET/CT images can be accurately prepared and effectively applied during RARP that might be a useful tool for tumor navigation. Images show prostate tumors and anatomy and might be a guide for the console surgeon. This is promising new technology that needs further study and validation.
Dimethyldioctadecylanimonium bentonite immobilized magnetic chitosan nanoparticles as an efficient adsorbent for vortex‐assisted magnetic dispersive micro‐solid‐phase extraction of celecoxib from human breast milk, plasma and urine samples
Authors: Majidi Seyedeh Maedeh , Hadjmohammadi Mohammad Reza
Published: May 2020

A polymer/layered silicate composite based on dimethyldioctadecylanimonium bentonite/chitosan magnetic nanoparticles was synthesized and characterized by field emission transmission electron microscopy, X‐ray diffraction and Fourier transform infrared spectrometry. The prepared nanocomposite was used to isolate and preconcentrate celecoxib from human breast milk, urine and plasma samples. In this method, dimethyldioctadecylanimonium bentonite increases the accessibility of binding sites and adsorption capacity by high microporosity and large surface area, that has been realized for the first time in a magnetic chitosan nanoparticle support. A fractional factorial design was utilized for screening the experimental parameters. The effective parameters were then optimized by Box–Behnken design. Under the optimized conditions, the developed method exhibited wide linear ranges of 5–500 μg L−1 for plasma and urine and 10–500 μg L−1 for breast milk samples with satisfactory recoveries in the range of 96.7–99.0%. Limit of detection and quantification of celecoxib were in the ranges 0.3–3.2 and 0.99–10.56, respectively. The enrichment factors were obtained in the ranges 64.5–66.0, while precisions were <3.7%.