bluuebunny/crossref_metadata_2025 huggingface dataset:
How society publishers can accelerate their transition to open access and align with Plan S
Authors: Wise Alicia , Estelle Lorraine
Published: January 2020

Wellcome, UK Research and Innovation, and the Association of Learned and Professional Society Publishers commissioned Information Power Ltd. to undertake a project to support society publishers to accelerate their transition to open access (OA) in alignment with Plan S and the wider move to accelerate immediate OA. This project is part of a range of activities that cOAlition S partners are taking forward to support the implementation of Plan S principles. The objective of this project was to explore with learned societies a range of potential strategies and business models through which they could adapt and thrive under Plan S. We consulted with society publishers through interviews, surveys, and workshops about the 27 business models and strategies identified during the project. We also surveyed library consortia about their willingness to support society publishers to make the transition to OA. Our key finding is that transformative agreements emerge as the most promising model because they offer a predictable, steady funding stream. We also facilitated pilot transformative agreement negotiations between several society publishers and library consortia. These pilots and a workshop of consortium representatives and society publishers informed the development of an OA transformative agreement toolkit. Our conclusion is that society publishers should consider all the business models this project has developed and should not automatically equate OA with article publication charges.
Building new societies: Insights and predictions from the 5th Wiley Society Member Survey
Authors: Roscoe Jonathan
Published: January 2020

The 5th Wiley Society Member Survey was conducted in May 2019. We received responses from 3,112 members who either consume, produce, utilize, or support scientific research, from more than 20 countries and across 40 disciplines. This year, we intentionally sought more responses from outside the USA and Western Europe than in the past, making the results more reflective of the diversity of the global research community. This made it clear that the research world is more disparate and, in some cases, such as in the Asia‐Pacific region, more contradictory than we have seen. Previously identified observations, such as an increase in respondents' simultaneous membership of multiple societies, have been consolidated, whereas others, such as the demand for support from societies for high standards of publishing ethics, are new to this survey. Central to the survey's findings is the continuing rise in researcher demand for open access and open research as tools for both consumption and production of research. Ultimately, by using these findings, this article suggests some strategies to enable societies to navigate their way through this new and constantly evolving world of academic research.
Otopathology in CHARGE syndrome
Authors: Chen Jenny X. , Nourmahnad Anahita , O'Malley Jennifer , Reinshagen Katherine , Nadol Joseph B. , Quesnel Alicia M.
Published: January 2020

Postmortem temporal bone computed tomography (CT) and histopathologic findings in an infant with CHARGE syndrome revealed bilateral cochleovestibular hypoplasia, including cochlear pathology relevant to cochlear implant candidacy. Both ears had absence of the superior semicircular canals (SCCs), severely hypoplastic posterior SCCs, and hypoplastic (right ear) or absent (left ear) lateral SCCs seen on CT and histopathology. Histopathology further revealed the absence of all SCC ampullae except the right lateral SCC ampulla and atrophic vestibular neuroepithelium in the saccule and utricle bilaterally. The right cochlea consisted of a basal turn with patent round window, and malformed middle turn (type IV cochlear hypoplasia), with a small internal auditory canal (IAC) but near normal cochlear nerve aperture (fossette). Quantification of spiral ganglion neurons (SGNs) on histologic sections revealed a reduced SGN population (35% of normal for age), but this ear would still have likely achieved benefit from a cochlear implant based on this population. The left cochlea consisted of only a basal turn with patent round window (type III cochlear hypoplasia) with a small IAC and very small cochlear nerve aperture. Notably, histology revealed that there were no SGNs in the cochlea, and therefore, this ear would not have been a good candidate for cochlear implantation.

Level of evidence: IV.
A novel cross‐shore transport mechanism revealed by subsurface, robotic larval mimics: Internal wave deformation of the background velocity field
Authors: Garwood Jessica C. , Lucas Andrew J. , Naughton Perry , Alford Matthew H. , Roberts Paul L. D. , Jaffe Jules S. , deGelleke Laura , Franks Peter J. S.
Published: January 2020

Coastal physical processes are essential for the cross‐shore transport of meroplanktonic larvae to their benthic adult habitats. To investigate these processes, we released a swarm of novel, trackable, subsurface vehicles, the Mini‐Autonomous Underwater Explorers (M‐AUEs), which we programmed to mimic larval depth‐keeping behavior. The M‐AUE swarm measured a sudden net onshore transport of 30–70 m over 15–20 min, which we investigated in detail. Here, we describe a novel transport mechanism of depth‐keeping plankton revealed by these observations. In situ measurements and models showed that, as a weakly nonlinear internal wave propagated through the swarm, it deformed surface‐intensified, along‐isopycnal background velocities downward, accelerating depth‐keeping organisms onshore. These higher velocities increased both the depth‐keepers' residence time in the wave and total cross‐shore displacement, leading to wave‐induced transports twice those of fully Lagrangian organisms and four times those associated with the unperturbed background currents. Our analyses also show that integrating velocity time series from virtual larvae or mimics moving with the flow yields both larger and more accurate transport estimates than integrating velocity time series obtained at a point (Eulerian). The increased cross‐shore transport of organisms capable of vertical swimming in this wave/background‐current system is mathematically analogous to the increase in onshore transport associated with horizontal swimming in highly nonlinear internal waves. However, the mechanism described here requires much weaker swimming speeds (mm s−1 vs. cm s−1) to achieve significant onshore transports, and meroplanktonic larvae only need to orient themselves vertically, not horizontally.
In‐lake transformations of dissolved organic matter composition in a subalpine lake do not change its biodegradability
Authors: Stadler Masumi , Ejarque Elisabet , Kainz Martin J.
Published: January 2020

In freshwater ecosystems, dissolved organic matter (DOM) originates from terrestrial and aquatic primary production, and its microbial biodegradability is expected to vary due to differences in its biogeochemical composition. However, the interaction of various DOM sources with the aquatic microbial population remains widely debated. Here, we performed laboratory bioassays, conducted in the dark for 20 d, to examine how changes in DOM composition influence its microbial biodegradability along a hydrological continuum (i.e., lake inlet, lake layers, and lake outlet) of a subalpine lake over four seasons. Despite a predominance of terrestrial DOM and lowest initial abundance of microorganisms, the highest microbial growth rates were observed at the lake inlet (0.0076 ± 0.0011 cells mL−1 h−1) across all seasons. DOM reactivity differed more with time (seasons) than with space (sampling sites) and DOM compositional differences showed higher degradability in upper lake layers, but not at the lake outlet. Additionally, gradual humification over incubation time was observed in almost all seasons and sites. Overall, an enhanced biodegradability of DOM was not detected even though lake sites were characterized by an autochthonous, presumably labile DOM signature. However, our results highlight the potential of thriving bacteria in terrestrial‐dominated DOM environments. This observation challenges a previous hypothesis that DOM of terrestrial origin is less accessible and more recalcitrant, while emphasizing the flexible response of aquatic systems to seasonal fluctuations.
Fused Silica with Embedded 2D‐Like Ag Nanoparticle Monolayer: Tunable Saturable Absorbers by Interparticle Spacing Manipulation
Authors: Li Rang , Pang Chi , Li Ziqi , Yang Ming , Amekura Hiroshi , Dong Ningning , Wang Jun , Ren Feng , Wu Qiang , Chen Feng
Published: January 2020

Saturable absorbers are key elements for generation of ultrafast laser pulses. The commercially available semiconductor saturable absorber mirrors are wavelength sensitive and with complex fabrication process and high cost. Fused silica is one of the basic materials for various optical applications. Plasmonic nanoparticles can be used to efficiently modulate the optical properties of dielectric materials owing to the enhanced field effects based on localized surface plasmonic resonance. Ion implantation is a direct technique to synthesize plasmonic nanoparticles inside dielectric materials, which can simultaneously tailor the optical nonlinearity of substrates significantly. In this work, Ag ion implantation into fused silica with tunable interparticle spacing is used to generate broadband optical nonlinearities and to endow silica with ultrafast saturable absorption property. This ion implantation forms a 2D‐like Ag nanoparticle monolayer buried inside fused silica wafer. The fused silica with embedded 2D‐like Ag nanoparticle monolayer is further applied as a new saturable absorber to generate ultrafast laser pulses with pulse duration of 27 ps and repetition rate of 6.5 GHz through the passive mode‐locking process. This work opens up a new route to develop low‐cost, highly stable saturable absorbers, and offers the possibility to build novel silica‐based photonic systems through nanoparticle spacing manipulation.
Thixomolded AZ91D and MRI153M magnesium alloys and their enhanced corrosion resistance
Authors: Buzolin Ricardo H. , Volovitch Polina , Maltseva Alina , Lamaka Sviatlana , Blawert Carsten , Mendis Chamini L. , Lohmüller Andreas , Kainer Karl U. , Hort Norbert
Published: January 2020

AZ91D and MRI153M alloys were produced by thixomolding. Their corrosion resistance is significantly higher than that of similar materials produced by ingot or die‐casting. A corrosion rate smaller than 0.2 mm/year in 5 wt% NaCl solution is measured for the thixomolded AZ91D alloy. The corrosion behaviour was evaluated using immersion tests, electrochemical impedance spectroscopy, hydrogen evolution, glow discharge optical emission spectroscopy, and atomic emission spectroelectrochemistry. A bimodal microstructure is observed for both alloys, with the presence of coarse primary α‐Mg grains, fine secondary α‐Mg grains, β‐phase, and other phases with a minor volume fraction. The amount of coarse primary α‐Mg is significantly higher for the AZ91D compared with the MRI153M. The network of β‐phase around the fine secondary α‐Mg grains is better established in the thixomolded AZ91D alloy. A combination of several factors such as the ratio of primary to secondary α‐Mg grains, localised corrosion or barrier effect due to other phases, as well as regions of preferential dissolution of the α‐Mg due to chemical segregation, are thought to be responsible for the high corrosion resistance exhibited by the thixomolded AZ91D and MRI153M.
Synthesis of Tri‐Aryl Methane Epoxy Resin Isomers and Their Cure with Aromatic Amines
Authors: Reyes Larry Q. , Issazadeh Salumeh , Zhang Jane , Dao Buu , Varley Russell J.
Published: January 2020

In this work, two tri‐aryl and one bi‐aryl epoxy resin, bis[(glycidyloxy)phenyl)]‐m‐xylene (BGOPmX), bis[(glycidyloxy)phenyl)]‐p‐xylene (BGOPpX), and bis(glycidyloxy) biphenyl (BGOBP) are synthesized and cured with methylene dianiline and 4,4′‐diamino diphenyl sulfone. Structure, property, and processing relationships are investigated and compared against diglycidyl ether of bis‐phenol F epoxy resin to better understand the impact of rigid and flexible subunits within the network structure. The rigid BGOBP epoxy network has a higher yield strain, and displays the highest glass transition temperature and a higher coefficient of thermal expansion (CTE) regardless of amine. Conversely, the more flexible tri‐aryl epoxy resins, BGOPmX and BGOPpX, have higher moduli and lower CTE. Properties such as yield stress and thermal degradation are relatively unaffected by structure. Results where possible are discussed in terms of the likely equilibrium packing density of the network and short range and segmental motions of the polymer networks determined from sub‐ambient dynamic mechanical analysis. Differences between BGOPmX and BGOPpX highlight the effect of minor variations in structure on reactivity, glass transition temperature, and compressive properties. This work clearly illustrates how fine control of chemical structure can tune the mechanical and thermal properties and reaction kinetics of network polymers.
The economic valuation of social aspects: A multicriteria approach based on input–output models1
Authors: Sanaú Jaime , Gómez‐Bahillo Carlos , Moreno‐Jiménez José María
Published: January 2020

Decision making on the suitability of public investment projects has traditionally been based on the study of their economic feasibility. Since the end of the 1970s, this has been complemented by a more holistic vision of reality in which social and environmental aspects are explicitly considered alongside economic factors. This paper proposes a new evaluation methodology that allows for the valuation of social and environmental factors in economic terms. The methodology is based on use values (direct, indirect, and potential) and nonuse values (bequest and existence) that are usually studied for an environmental evaluation. The resulting economic value is obtained by the utilization of (a) input–output models to calculate the direct use value in monetary terms and (b) multicriteria techniques (especially the analytic hierarchy process) and comparative models to estimate the remaining use (indirect and potential) and nonuse values (bequest and existence). The methodology is applied to a real‐life problem in Aragon.
Normal Temporal Discrimination in Musician's Dystonia Is Linked to Aberrant Sensorimotor Processing
Authors: Maguire Fiachra , Reilly Richard B. , Simonyan Kristina
Published: January 2020

Objectives

Alterations in sensory discrimination are a prominent nonmotor feature of dystonia. Abnormal temporal discrimination in focal dystonia is considered to represent its mediational endophenotype, albeit unclear pathophysiological correlates. We examined the associations between the visual temporal discrimination threshold (TDT) and brain activity in patients with musician's dystonia, nonmusician's dystonia, and healthy controls.

Methods

A total of 42 patients and 41 healthy controls participated in the study. Between‐group differences in TDTzscores were computed using inferential statistics. Statistical associations of TDTzscores with clinical characteristics of dystonia and resting‐state functional brain activity were examined using nonparametric rank correlations.

Results

The TDTzscores of healthy controls were significantly different from those of patients with nonmusician's dystonia, but not of patients with musician's dystonia. Healthy controls showed a significant relationship between normal TDT levels and activity in the inferior parietal cortex. This relationship was lost in all patients. Instead, TDTzscores in musician's dystonia established additional correlations with activity in premotor, primary somatosensory, ventral extrastriate cortices, inferior occipital gyrus, precuneus, and cerebellum, whereas nonmusician's dystonia showed a trending correlation in the lingual gyrus extending to the cerebellar vermis. There were no significant relationships between TDTzscores and dystonia onset, duration, or severity.

Conclusions

TDT assessment as an endophenotypic marker may only be relevant to nonmusician forms of dystonia because of the lack of apparent alterations in musician's dystonia. Compensatory adaptation of neural circuitry responsible for TDT processing likely adjusted the TDT performance to the behaviorally normal levels in patients with musician's dystonia, but not nonmusician's dystonia. © 2020 International Parkinson and Movement Disorder Society
Role of Glial Cell Line‐Derived Neurotrophic Factor in the Maintenance of Adult Mesencephalic Catecholaminergic Neurons
Authors: Enterría‐Morales Daniel , López‐López Ivette , López‐Barneo José , d'Anglemont de Tassigny Xavier
Published: January 2020

Background

The glial cell line‐derived neurotrophic factor has a potent neuroprotective action on mesencephalic dopamine neurons, which are progressively lost in Parkinson's disease. Intrastriatal administration of this factor is a promising therapy for Parkinson's disease. Glial cell line‐derived neurotrophic factor is naturally produced in restricted cerebral regions, such as the striatum, septum, and thalamus; however, its effects in the adult brain remain under debate.

Objectives

We sought to clarify the physiologic role of endogenous glial cell line‐derived neurotrophic factor in the survival of catecholaminergic neurons of the substantia nigra pars compacta and the locus coeruleus in adult mice.

Methods

We used 2 new Cre recombinase‐based mouse models to delete a floxed–glial cell line‐derived neurotrophic factor gene. The first model had Cre expression in the parvalbumin expressing interneurons, as these cells represent the major source of striatal glial cell line‐derived neurotrophic factor. The second model was an estrogen receptor 2‐based inducible Cre triggered by tamoxifen at 2 months of age.

Results

We found that the floxed–glial cell line‐derived neurotrophic factor gene was resilient to ablation by Cre‐induced recombination and that parvalbumin‐driven Cre was particularly inefficient to do so. The inducible‐Cre model allowed an average 70% to 80% reduction in glial cell line‐derived neurotrophic factor messenger ribonucleic acid and protein in striatum and septum with moderate significant loss of catecholamine neurons in the nigrostriatal pathway and, more markedly, in the locus coeruleus. This was accompanied with mild locomotor decline.

Conclusions

Our data support qualitatively the view that brain glial cell line‐derived neurotrophic factor is needed for the maintenance of adult central catecholaminergic neurons. © 2020 International Parkinson and Movement Disorder Society
The Use of the Index of Ideality of Correlation to Build Up Models for Bioconcentration Factor
Authors: Toropova Alla P. , Duchowicz Pablo R. , Saavedra Laura M. , Castro Eduardo A. , Toropov Andrey A.
Published: January 2020

We establish a QSPR analysis for the bioconcentration factor of 851 heterogeneous structural compounds. Linear models are proposed via two different approaches: i. the optimal descriptor method implemented in CORAL, and ii. multivariable linear regressions on the best molecular descriptors found with the Replacement Method on 44,216 structural descriptors. Such variables are derived with different freely available softwares, such as PaDEL, PyDescriptor, Mold2, QuBiLs‐MAS and ISIDA/Fragmentor. The same validation set is employed in order to compare the predictive performance between the so‐obtained CORAL and RM based models. Finally, the comparison of several models for the bioconcentration factor confirms the ability of the so‐called index of ideality of correlation to be a criterion of predictive potential in Quantitative Structure‐Property Relationships.
Combined use of dbcAMP and IBMX minimizes the damage induced by a long‐term artificial meiotic arrest in mouse germinal vesicle oocytes
Authors: Wu Xue‐Chen , Han Zhe , Hao Xin , Zhao Yi‐Tong , Zhou Cheng‐Jie , Wen Xin , Liang Cheng‐Guang
Published: January 2020

Phosphodiesterase (PDE)‐mediated reduction of cyclic adenosine monophosphate (cAMP) activity can initiate germinal vesicle (GV) breakdown in mammalian oocytes. It is crucial to maintain oocytes at the GV stage for a long period to analyze meiotic resumption in vitro. Meiotic resumption can be reversibly inhibited in isolated oocytes by cAMP modulator forskolin, cAMP analog dibutyryl cAMP (dbcAMP), or PDE inhibitors, milrinone (Mil), Cilostazol (CLZ), and 3‐isobutyl‐1‐methylxanthine (IBMX). However, these chemicals negatively affect oocyte development and maturation when used independently. Here, we used ICR mice to develop a model that could maintain GV‐stage arrest with minimal toxic effects on subsequent oocyte and embryonic development. We identified optimal concentrations of forskolin, dbcAMP, Mil, CLZ, IBMX, and their combinations for inhibiting oocyte meiotic resumption. Adverse effects were assessed according to subsequent development potential, including meiotic resumption after washout, first polar body extrusion, early apoptosis, double‐strand DNA breaks, mitochondrial distribution, adenosine triphosphate levels, and embryonic development. Incubation with a combination of 50.0 μM dbcAMP and 10.0 μM IBMX efficiently inhibited meiotic resumption in GV‐stage oocytes, with low toxicity on subsequent oocyte maturation and embryonic development. This work proposes a novel method with reduced toxicity to effectively arrest and maintain mouse oocytes at the GV stage.
Early Weaning Effects on Survival, Growth, and Histopathology of Larval Sterlet Acipenser ruthenus
Authors: Laczynska Beata , Siddique Mohammad Abdul Momin , Ziomek Elzbieta , Shelton William L , Fopp-Bayat Dorota
Published: January 2020

Weaning of fish is a critical stage during larval rearing and could cause high mortality. Therefore, proper larval weaning period selection is crucial for the success of larviculture. This study aimed to find the effect of weaning on growth performance, histopathological features, and mortality rates in larvae of Sterlet Acipenser ruthenus. The experimental rearing was conducted from 7 to 38 d posthatch (dph) at a mean temperature of 18°C in a recirculating system. The experiment was carried out in three groups (each with three replicates) and placed in nine tanks (22 L) at a density of 10 individuals/L. The diet groups were made up of group C in which larvae were fed with nauplii of brine shrimp Artemia spp., group F7 in which larvae were weaned to dry feed 15 dph, and group F that was fed with dry feed throughout the experimental trial. During 15–38 dph, total wet body weight and total length were lowest in the group fed with formulated feed. Survival rate of larvae in group F7 was 90.45% and 70.05% during 7–14 and 15–22 dph, respectively. On the other hand, the survival rate of larvae fed only Artemia nauplii (group C) or formulated feed (group F) was 86.14% and 70.45% during 7–14 dph and 84.55% and 78.41% during 15–22 dph, respectively. The maximum height of the enterocytic epithelium was found in the individuals in group F7 (mean ± SD = 33.80 ± 2.56 μm). The average height of enterocytes of group F7 (n =30 fish) larvae were significantly increased at 15, 23, and 38 dph compared with the larvae fed with formulated feed and live feed, but no significant changes were observed in the liver cells, including in the diameter of hepatocytes and their nuclei. This study provides evidence that Sterlet larvae should be fed with Artemia nauplii at 7–15 dph because fish gain a higher wet body weight and total length and develop a better liver and digestive tract.
Voluntary exercise improves voiding function and bladder hyperalgesia in an animal model of stress‐induced visceral hypersensitivity: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study
Authors: Sanford Melissa T. , Yeh Jih‐chao , Mao Jackie J. , Guo Yumei , Wang Zhuo , Zhang Rong , Holschneider Daniel P. , Rodriguez Larissa V.
Published: January 2020

Objective

The underlying mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) is not well understood and evaluation of current therapeutic interventions has not identified any generally effective treatments. Physical activity has shown beneficial effects on individuals suffering from chronic pain. Anxiety‐prone rats exposed to water avoidance stress (WAS) develop urinary frequency and lower bladder sensory thresholds with high face and construct validity for the study of IC/BPS. The aim of this study was to evaluate the role of chronic voluntary exercise on urinary frequency, voiding function, and hyperalgesia in animals exposed to WAS.

Materials and Methods

Twenty‐six female Wistar‐Kyoto rats were exposed to WAS and thereafter randomized to either voluntary exercise for 3 weeks or sedentary groups. Voiding parameters were assessed at baseline, post‐WAS, and weekly for 3 weeks. Before euthanasia, the animals underwent cystometrogram (CMG), external urinary sphincter electromyography, and assessment of visceromotor response (VMR) to isotonic bladder distension (IBD).

Results

WAS exposure resulted in adverse changes in voiding parameters. Compared with sedentary animals, animals in the voluntary exercise group had improved voiding parameters during metabolic cage and CMG testing, as well as improved bladder sensory thresholds as determined by VMR during IBD.

Conclusion

Voluntary exercise in an animal model of chronic stress leads to improvement in voiding function and visceral bladder hyperalgesia.
Global cracking elements: A novel tool for Galerkin‐based approaches simulating quasi‐brittle fracture
Authors: Zhang Yiming , Mang Herbert A.
Published: January 2020

Following the so‐called cracking elements method (CEM), we propose a novel Galerkin‐based numerical approach for simulating quasi‐brittle fracture, named global cracking elements method (GCEM). For this purpose the formulation of the original CEM is reorganized. The new approach is embedded in the standard framework of the Galerkin‐based finite‐element method (FEM), which uses disconnected element‐wise crack openings for capturing crack initiation and propagation. The similarity between the proposed global cracking elements (GCEs) and the standard nine‐node quadrilateral element (Q9) suggests a special procedure: the degrees of freedom of the center node of the Q9, originally defining the displacements, are “borrowed” to describe the crack openings of the GCE. The proposed approach does not need remeshing, enrichment, or a crack‐tracking strategy, and it avoids a precise description of the crack tip. Several benchmark tests provide evidence that the new approach inherits from the CEM most of the advantages. The numerical stability and robustness of the GCEM are better than the ones of the CEM. However, presently only quadrilateral elements with nonlinear interpolations of the displacement field can be used.
Optimizing Patient Outcomes with PD‐1/PD‐L1 Immune Checkpoint Inhibitors for the First‐Line Treatment of Advanced Non–Small Cell Lung Cancer
Authors: La‐Beck Ninh M. , Nguyen Dung T. , Le Alex D. , Alzghari Saeed K. , Trinh Saralinh T.
Published: January 2020

The rapidly expanding repertoire of immune checkpoint inhibitors (ICIs) now includes two agents, pembrolizumab and atezolizumab, approved for first‐line treatment of advanced non–small cell lung cancer (aNSCLC) as monotherapy or as part of chemoimmunotherapy. This review summarizes the clinical evidence supporting these indications, with a focus on strategies to optimize patient outcomes. These strategies include patient and tumor factors, adverse‐effect profiles, pharmacokinetic and pharmacodynamic drug interactions, and quality of life and cost‐effectiveness considerations. We performed a systematic literature search of the PubMed, Scopus, and Google Scholar databases, as well as a search of the conference proceedings of the American Society of Clinical Oncology, European Society for Medical Oncology, and American Association for Cancer Research (through August 31, 2019). The addition of ICIs to conventional chemotherapy as first‐line treatment against aNSCLC is now part of the standard of care options. However, even though ICIs may be cost‐effective in patients with aNSCLC, high drug and other associated costs can still be a barrier to treatment for patients. Moreover, the adverse‐effect profiles of ICIs differ significantly from conventional chemotherapy, and some immune‐related adverse effects may have a lasting impact on quality of life. Therefore, in adhering to a patient‐centered model of care, clinicians should be mindful of patient‐ and treatment‐specific factors when considering therapeutic options for patients with aNSCLC. Although the role of the immune system in cancer progression and regression has not been fully elucidated, the full clinical potential of immunotherapeutics in the treatment of cancer likely remains to be unleashed.
Emerging Roles and Research Tools of Atypical Ubiquitination
Authors: Huang Qiuling , Zhang Xiaofei
Published: January 2020

Ubiquitination is a posttranslational modification characterized by the covalent attachment of ubiquitin molecules to protein substrates. The ubiquitination modification process is reversible, dynamic, and involved in the regulation of various biological processes, such as autophagy, inflammatory responses, and DNA damage responses. The forms of ubiquitin modification are very diverse, incorporating either a single ubiquitin molecule or a complicated ubiquitin polymer, and different types of ubiquitination usually elicit corresponding cellular responses. The development of research tools and strategies has afforded more detailed insight into atypical ubiquitin signaling pathways that were previously poorly understood. Here, an update on the understanding of atypical ubiquitin chain signaling pathways is provided and the recent development of representative research tools for ubiquitin systems is discussed. In addition, the future challenges in ubiquitin research are reflected on and summarized.
A complex interprofessional intervention to improve the management of painful procedures in neonates
Authors: Balice‐Bourgois Colette , Newman Christopher J. , Simonetti Giacomo D. , Zumstein‐Shaha Maya
Published: January 2020

During hospitalization, neonates are exposed to a stressful environment and a high number of painful procedures. If pain is not treated adequately, short‐ and long‐term complications may develop. Despite evidence about neonatal pain and available guidelines, procedural pain remains undertreated. This gap between research and practice is mostly due to limited implementation of evidence‐based knowledge and time constraints. This study describes in detail the development process of a complex interprofessional intervention to improve the management of procedural pain in neonates called NEODOL© (NEOnato DOLore). The framework of the Medical Research Council (MRC) for the development and evaluation of complex interventions was used as a methodological guide for the design of the NEODOL© intervention. The development of the intervention is based on several steps and multiple methods. To report this process, we used the Criteria for Reporting the Development of Complex Interventions in Healthcare (CReDECI 2). Additionally, we evaluated the content of the intervention using a Delphi method to obtain consensus from experts, stakeholders, and parents. The complex interprofessional intervention, NEODOL©, is developed and designed for three groups: healthcare professionals, parents, and neonates for a level IIb neonatal unit at a regional hospital in southern Switzerland. A total of 16 panelists participated in the Delphi process. At the end of the Delphi process, the panelists endorsed the NEODOL© intervention as important and feasible. Following the MRC guidelines, a multimethod process was used to develop a complex interprofessional intervention to improve the management of painful procedures in newborns. Complex interprofessional interventions need theoretical bases, careful development, and integration of stakeholders to provide a comprehensive approach. The NEODOL intervention consists of promising components and has the potential to improve the management of painful procedures and should facilitate the knowledge translation into practice.
Site‐specific rapid deamidation and isomerization in human lens αA‐crystallin in vitro
Authors: Takata Takumi , Ha Seongmin , Koide Tamaki , Fujii Noriko
Published: January 2020

Recent studies have suggested that the isomerization/racemization of aspartate residues in proteins increases in aged tissues. One such residue is Asp151 in lens‐specific αA‐crystallin. Although many isomerization/racemization sites have been reported in various proteins, the factors that lead to those modifications in proteins in vivo remain obscure. Therefore, an in vitro system is needed to assess the mechanisms of modifications of Asp under various conditions. Deamidation of Asn to Asp in proteins occurs more rapidly than isomerization/racemization of Asp, although the reaction passes through the same intermediate in both pathways. Here, therefore, we replaced Asp151 in human lens αA‐crystallin with Asn by using site‐directed mutagenesis. The recombinant protein was expressed in Escherichia coli and used to investigate the deamidation/isomerization/racemization of Asn151 after incubation at 50°C for various durations and under different pH. After incubation, the mutant αA‐crystallin was subjected to enzymatic digestion followed by liquid chromatography–MS/MS to evaluate the ratio of modifications in Asn151‐containing peptides. The Asp151Asn αA‐crystallin mutant showed rapid deamidation to Asp with the formation of specific Asp isomers. In particular, deamidation increased greatly under basic conditions. By contrast, subunit–subunit interactions between αA‐crystallin and αB‐crystallin had little effect on the modification of Asn151. Our findings suggest that the Asp151Asn αA‐crystallin mutant represents a good in vitro model protein to assess deamidation, isomerization, and the racemization intermediates. Furthermore, our in vitro results show a different trend from in vivo data, implying the presence of specific factors that induce racemization from L‐Asp to D‐Asp residues in vivo.
Allosteric inhibitors of Mycobacterium tuberculosis tryptophan synthase
Authors: Michalska Karolina , Chang Changsoo , Maltseva Natalia I. , Jedrzejczak Robert , Robertson Gregory T. , Gusovsky Fabian , McCarren Patrick , Schreiber Stuart L. , Nag Partha P. , Joachimiak Andrzej
Published: January 2020

Global dispersion of multidrug resistant bacteria is very common and evolution of antibiotic‐resistance is occurring at an alarming rate, presenting a formidable challenge for humanity. The development of new therapeuthics with novel molecular targets is urgently needed. Current drugs primarily affect protein, nucleic acid, and cell wall synthesis. Metabolic pathways, including those involved in amino acid biosynthesis, have recently sparked interest in the drug discovery community as potential reservoirs of such novel targets. Tryptophan biosynthesis, utilized by bacteria but absent in humans, represents one of the currently studied processes with a therapeutic focus. It has been shown that tryptophan synthase (TrpAB) is required for survival of Mycobacterium tuberculosis in macrophages and for evading host defense, and therefore is a promising drug target. Here we present crystal structures of TrpAB with two allosteric inhibitors of M. tuberculosis tryptophan synthase that belong to sulfolane and indole‐5‐sulfonamide chemical scaffolds. We compare our results with previously reported structural and biochemical studies of another, azetidine‐containing M. tuberculosis tryptophan synthase inhibitor. This work shows how structurally distinct ligands can occupy the same allosteric site and make specific interactions. It also highlights the potential benefit of targeting more variable allosteric sites of important metabolic enzymes.
Quantitative analysis of the relationship between structure and antioxidant activity of tripeptides
Authors: Uno Shinya , Kodama Daisuke , Yukawa Hiroko , Shidara Hiroyuki , Akamatsu Miki
Published: January 2020

Peptides from enzymatic hydrolysates of food proteins exhibit significant antioxidant activity. Several studies have attempted to determine the factors contributing to the antioxidant activity of peptides; however, the physicochemical properties and factors essential for the antioxidant activity of peptides are still unclear. In this study, in order to clarify the factors important for peptide antioxidant activity based on the properties of component amino acids, 55 tripeptides were synthesized from 20 natural amino acids and their antioxidant activity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay system. The tripeptides were divided into two data sets: a training set comprising 50 compounds and a validated set comprising five compounds. The structure‐activity relationship of the training set was then analyzed using classical quantitative structure‐activity relationship (QSAR) analysis. The study findings demonstrate that the presence of a cysteine residue at any position, an aromatic amino acid at the C‐terminus, higher hydrophobicity of the N‐terminal residue, and smaller HOMO‐LUMO energy gap of the middle residue can significantly enhance the antioxidant activity. The activities of the five validated compounds were predicted using the constructed QSAR model, and a good correlation between measured and predicted activities was observed. The information obtained from the QSAR model could be useful for effective production of antioxidant peptides from food proteins such as egg white proteins.
Electronic and Ionic Electric Field Screening and Persistent Built‐In Electric Field in Carbon Nanotube/PCBM Films
Authors: Jašinskas Vidmantas , Oberndorfer Florian , Hertel Tobias , Gulbinas Vidmantas
Published: January 2020

The application of carbon nanotubes in electronic devices requires detailed knowledge of their electrical properties. Herein, the long‐lasting electric field‐induced polarization of single‐wall carbon nanotube (SWCNT) networks is demonstrated. It is found that electric voltage applied to the films of SWCNTs and their blends with [6,6]‐phenyl‐C61‐butyric acid methyl ester (PCBM) creates persistent polarization that partly screens the external electric field and creates a built‐in electric field of the opposite direction remaining for several days. The built‐in electric field has caused the appearance of an open‐circuit photovoltage and a short‐circuit photocurrent under the sample illumination at zero applied voltage. The built‐in field showed a clearly bicomponential decay. The short tens of microseconds component is attributed to the electronic polarization, while the long‐lived component, which decreases at low temperatures, is attributed to the temperature‐assisted motion of ions.
Enhanced Strain Relaxation in AlGaN Layers Grown on Sputter‐Based AlN Templates
Authors: Mogami Yosuke , Osawa Atsushi , Ozaki Kazuto , Tanioka Yukitake , Maeoka Atsushi , Itokazu Yuri , Kuwaba Shunsuke , Jo Masafumi , Maeda Noritoshi , Yaguchi Hiroyuki , Hirayama Hideki
Published: January 2020

Strain plays a crucial role in the performance of ultraviolet (UV) optoelectronic devices. The strain states of AlGaN layers grown on different AlN templates are investigated. Two types of AlN templates are prepared: one is grown solely by metal‐organic chemical vapor deposition (MOCVD), and the other is fabricated with the combination of direct current (DC) sputtering, high‐temperature annealing, and MOCVD growth. The qualities of 4 μm‐thick MOCVD AlN and 1.2 μm‐thick sputter‐based AlN are almost equivalent in terms of dislocation density and surface morphology. However, the strain relaxation ratio of the AlGaN layer is higher for the 1.2 μm sputter‐based AlN than the 4 μm MOCVD AlN, indicating that the strain state depends on the total thickness of the epilayers on the sapphire substrate. In addition, it is found that the curvature of the sample at room temperature is governed mainly by the thickness of the AlGaN layer. As a result, sputter‐based AlN templates allow for the enhanced strain relaxation of the AlGaN layer with a small sample bowing.
Effects of an engineered log jam on spatial variability of the flow field across submergence depths
Authors: L'Hommedieu William , Tullos Desirée , Jones Julia
Published: January 2020

Engineered log jams (ELJs) are commonly implemented in rivers to diversify fish habitat, but few studies have verified the hydraulic benefits of ELJs by assessing their effects on the spatial variability and turbulence structure of the flow field. This field and modelling study assessed the effects of an ELJ on various characteristics of the flow field with increasing submergence. A 2‐D hydrodynamic model was applied to simulate flow conditions of the Calapooia River, Oregon, with an ELJ installed at the upstream end of a meander. Output was analyzed using coherent flow structure identification, maps of turbulence measures, and wavelet analysis along linear transects. At the highest discharge (62% ELJ submergence), more and smaller coherent flow structures were identified than in the no ELJ model run, but the magnitudes of turbulence metrics were unaffected. At low flow (1% jam submergence), the presence of the ELJ did not affect the number of coherent flow structures identified and produced only small and localized effects on turbulence measures. Taken together, results indicate that the ELJ primarily affected the flow field by increasing the number of flow structures at higher discharges and submergence depths. However, these changes were small and local to the ELJ. The limited effects of this wood jam over limited spatial scales raise questions about the conditions under which such structures increase hydraulic diversity and highlight the need for more detailed understanding on spatial variability around habitat structures with complex shapes.
Asymptotic normality in random graphs with given vertex degrees
Authors: Janson Svante
Published: January 2020

We consider random graphs with a given degree sequence and show, under weak technical conditions, asymptotic normality of the number of components isomorphic to a given tree, first for the random multigraph given by the configuration model and then, by a conditioning argument, for the simple uniform random graph with the given degree sequence. Such conditioning is standard for convergence in probability, but much less straightforward for convergence in distribution as here. The proof uses the method of moments, and is based on a new estimate of mixed cumulants in a case of weakly dependent variables. The result on small components is applied to give a new proof of a recent result by Barbour and Röllin on asymptotic normality of the size of the giant component in the random multigraph; moreover, we extend this to the random simple graph.
Evolutionary analysis on structural characteristics of water resource system in basins of Northern China
Authors: Lu Shibao , Zhang Xiaoling , Tang Yao
Published: January 2020

The overdevelopment of water resources has caused the deterioration of the river ecology and environment, resulting in increasing water shortages. This has become one of the key factors that restricts the sustainable development of the social economy and ecological environment of the region. The water network system of the Songhua, Liaohe, Yellow, and Haihe river basins is analyzed by using ecological network analysis for the period 2004–2017. According to our findings, the network structures of various river basins present a relevant gap from its equilibrium value; thus, the water resources have not reached the state of sustainable use. By comparing the value of the water system in Songliao, Yellow, and Haihe river basins with aopt, we found that only the water network structure of the Songliao River Basin is close to the point of equilibrium. Therefore, we recommend to improve water‐use efficiency and reduce production and domestic water consumption by adjusting water prices, carrying out agricultural water‐saving irrigation, and increasing the use of industrial circulating water. This set of measures would ensure sufficient ecological water consumption in the basin, in order to meet the needs of a healthy and sustainable development of the ecological environment.
NanoSIMS image enhancement by reducing random noise using low‐rank method
Authors: Lin Yi , Hao Jialong , Miao Zhongzheng , Zhang Jinhai , Yang Wei
Published: January 2020

NanoSIMS images are usually affected by random noises because of various types of sources, which degrade the quality of ion images and increase the uncertainty of the geochemical interpretations. Here, we applied the weighted nuclear norm minimization (WNNM) method to reduce the random noise in the NanoSIMS image. The low‐rank property of the image is fully considered to suppress random noise while retaining reliable details of weak signals. Numerical experiments on four different kinds of NanoSIMS ion images show that the denoising ability of the WNNM method is superior to that of the median filter, no matter the size of the filtering windows used (eg, 3 × 3, 5 × 5, and 7 × 7). The WNNM method can reduce random noise while preserving the most critical details in the original NanoSIMS observations, which can significantly enhance reliability when distinguishing critical boundaries and structures.
Facile Synthesis of 1,4‐Disubstituted 1,2,3‐Triazoles Using Tetraaza‐coordinated Copper(II) Complexes as Efficient Catalysts
Authors: Green Samuel Angel , Jebasingh Bhagavathsingh
Published: January 2020

We report the class of tetraaza coordinated copper(II) complexes of 1,10‐phenanthroline ([CuII(L1)2]ClO4), 2,2’‐bipyridine ([CuII(L2)2]ClO4) and 1,4,7,10‐tetraazacyclo‐dodecane ([CuII(L3)](ClO4)2) are employed as efficient catalysts for the Copper Catalyzed Azide Acetylene Cycloaddition (CuIIAAC) reaction. The complex [CuII(L1)2]ClO4 showed high catalytic activity with the reductant for [3+2] Huisgen cycloaddition of terminal alkyne and various azides due to its structural orientation. The corresponding 1,4‐disubstituted‐1,2,3‐triazoles are isolated in good yield (12 examples) at room temperature without the impact of additives. These complexes also facilitate the stabilization of in‐situ generated Cu(I)L species to a greater extent due to their ligand framework.
System of Diagnostic Systems framework and its application to the disharmony in Indonesian national security
Authors: Muhammad Ade , Putro Utomo S. , Siallagan Manahan , Kijima Kyoichi , Wasesa Meditya
Published: January 2020

Although many strategic problems are highly complex and dynamic, available strategic frameworks fail to provide satisfactory solution recommendation. To provide a strategic solution to this highly complex and dynamic problem contexts, we propose a new strategic framework called the System of Diagnostic Systems (SODS). As an empirical case, we apply the SODS framework to analyse the highly complex disharmony issue in the national security of the Republic of Indonesia. Using SODS, we can analyse the problem contexts of three phases of Indonesian security development in a precise manner. Based on the problem's parameterization (i.e., participants, complexity level, comprehensibility, and rationality), the SODS framework can provide the appropriate strategy and tools to mitigate the complex issue. The SODS recommendations were validated by a number of problem domain experts.