bluuebunny/crossref_metadata_2025 huggingface dataset:
Peacebuilding and transformational change in Nigeria's oil region
Authors: Okoi Obasesam
Published: October 2019

This article draws on primary sources to examine postconflict transformations in Nigeria's oil region. The overarching goal of the article is to evaluate the impact of Nigeria's disarmament, demobilization, and reintegration program and its effectiveness as a vehicle for peacebuilding in the oil region, focusing specifically on the changes it has brought to the lives of former insurgents at the cultural, intrapersonal, structural, and interpersonal (CISI) levels. This study introduces the CISI model of conflict transformation to put these changes into context and explain why they are crucial for understanding peacebuilding and transformational change.
Successful treatment of idiopathic mast cell activation syndrome with low‐dose Omalizumab
Authors: Berry Renee , Hollingsworth Peter , Lucas Michaela
Published: October 2019

Objectives

Idiopathic mast cell disorders, a recently defined and recognised syndrome in clinical practice, are similar to the previously termed non‐clonal mast cell disorder. Patients with idiopathic mast cell activation syndrome (MCAS) suffer all the classical signs of mast cell activation but do not have evidence of mast cell clonality. Furthermore, treatment of these patients can be limited and burdensome in those with refractory symptoms.

Methods

Here, we describe treatment of a patient with idiopathic MCAS utilising a single monthly subcutaneous injection of omalizumab and review the current classification and therapeutic options for clonal and non‐clonal MCAS.

Results

Low‐dose omalizumab treatment has successfully led to a 5‐year, sustained clinical response, controlled debilitating symptoms of mast cell activation and allowed for reintroduction and long‐term maintenance of bee venom subcutaneous immunotherapy.

Conclusion

Low‐dose omalizumab of 150 mg monthly should be considered for maintenance management of patients with idiopathic MCAS for its cost and quality‐of‐life benefits.
Book Review
Authors: Sanford Amy Aldridge
Published: October 2019

Top Ten Ways to Be a Great Leader
Spatial scale affects novel and disappeared climate change projections in Alaska
Authors: Morrison Bailey D. , Heath Katy , Greenberg Jonathan A.
Published: October 2019

The formation of novel and disappeared climates between the last glacial maximum (LGM) and the present is important to consider to understand the expansion and contraction of species niches and distributions, as well as the formation and loss of communities and ecological interactions over time. Our choice in climate data resolution has the potential to complicate predictions of the ecological impacts of climate change, since climate varies from local to global scales and this spatial variation is reflected in climate data. To address this issue, we downscaled LGM and modern (1975–2005) 30‐year averaged climate data to 60‐m resolution for the entire state of Alaska for 10 different climate variables, and then upsampled each variable to coarser resolutions (60 m to 12 km). We modeled the distributions of novel and disappeared climates to evaluate the locations and fractional area of novel and disappeared climates for each of our climate variables and resolutions. Generally, novel and disappeared climates were located in southern Alaska, although there were cases where some disappeared climates existed within coastal and interior Alaska. Climate resolution affected the fractional area of novel and disappeared climates in three patterns: As the spatial resolution of climate became coarser, the fractional area of novel and disappeared climates (a) increased, (b) decreased, or (c) had no explainable relationship. Overall, we found the use of coarser climate data increased the fractional area of novel and disappeared climates due to decreased environmental variability and removal of climate extremes. Our results reinforce the importance of downscaling coarse climate data and suggest that studies analyzing the effects of climate change on ecosystems may overestimate or underestimate their conclusions when utilizing coarse climate data.
Fine‐scale substrate heterogeneity in green roof plant communities: The constraint of size
Authors: Vasl Amiel , Schindler Bracha Y. , Kadas Gyongyver J. , Blaustein Leon
Published: October 2019

Heterogeneity–diversity relationship (HDR) is commonly shown to be positive in accordance with classic niche processes. However, recent soil‐based studies have often found neutral and even negative HDRs. Some of the suggested reasons for this discrepancy include the lack of resemblance between manipulated substrate and natural settings, the treated areas not being large enough to contain species' root span, and finally limited‐sized plots may not sustain focal species’ populations over time. Vegetated green roofs are a growing phenomenon in many cities that could be an ideal testing ground for this problem. Recent studies have focused on the ability of these roofs to sustain stable and diverse plant communities and substrate heterogeneity that would increase niches on the roof has been proposed as a method to attain this goal. We constructed an experimental design using green roof experimental modules (4 m2) where we manipulated mineral and organic substrate component heterogeneity in different subplots (0.25 m2) within the experimental module while maintaining the total sum of mineral and organic components. A local annual plant community was seeded in the modules and monitored over three growing seasons. We found that plant diversity and biomass were not affected by experimentally created substrate heterogeneity. In addition, we found that different treatments, as well as specific subplot substrates, had an effect on plant community assemblages during the first year but not during the second and third years. Substrate heterogeneity levels were mostly unchanged over time. The inability to retain plant community composition over the years despite the maintenance of substrate differences supports the hypothesis that maintenance of diversity is constrained at these spatial scales by unfavorable dispersal and increased stochastic events as opposed to predictions of classic niche processes.
Bayesian model selection for spatial capture–recapture models
Authors: Dey Soumen , Delampady Mohan , Gopalaswamy Arjun M.
Published: October 2019

A vast amount of ecological knowledge generated over the past two decades has hinged upon the ability of model selection methods to discriminate among various ecological hypotheses. The last decade has seen the rise of Bayesian hierarchical models in ecology. Consequently, commonly used tools, such as the AIC, become largely inapplicable and there appears to be no consensus about a particular model selection tool that can be universally applied. We focus on a specific class of competing Bayesian spatial capture–recapture (SCR) models and apply and evaluate some of the recommended Bayesian model selection tools: (1) Bayes Factor—using (a) Gelfand‐Dey and (b) harmonic mean methods, (2) Deviance Information Criterion (DIC), (3) Watanabe‐Akaike's Information Criterion (WAIC) and (4) posterior predictive loss criterion. In all, we evaluate 25 variants of model selection tools in our study. We evaluate these model selection tools from the standpoint of selecting the “true” model and parameter estimation. In all, we generate 120 simulated data sets using the true model and assess the frequency with which the true model is selected and how well the tool estimates N (population size), a parameter of much importance to ecologists. We find that when information content is low in the data, no particular model selection tool can be recommended to help realize, simultaneously, both the goals of model selection and parameter estimation. But, in general (when we consider both the objectives together), we recommend the use of our application of the Bayes Factor (Gelfand‐Dey with MAP approximation) for Bayesian SCR models. Our study highlights the point that although new model selection tools are emerging (e.g., WAIC) in the applied statistics literature, those tools based on sound theory even under approximation may still perform much better.
Diet‐based assortative mating through sexual imprinting
Authors: Delaney Emily K. , Hoekstra Hopi E.
Published: October 2019

Speciation is facilitated by “magic traits,” where divergent natural selection on such traits also results in assortative mating. In animal populations, diet has the potential to act as a magic trait if populations diverge in consumed food that incidentally affects mating and therefore sexual isolation. While diet‐based assortative mating has been observed in the laboratory and in natural populations, the mechanisms causing positive diet‐based assortment remain largely unknown. Here, we experimentally created divergent diets in a sexually imprinting species of mouse, Peromyscus gossypinus (the cotton mouse), to test the hypothesis that sexual imprinting on diet could be a mechanism that generates rapid and significant sexual isolation. We provided breeding pairs with novel garlic‐ or orange‐flavored water and assessed whether their offspring, exposed to these flavors in utero and in the nest before weaning, later preferred mates that consumed the same flavored water as their parents. While males showed no preference, females preferred males of their parental diet, which is predicted to yield moderate sexual isolation. Thus, our experiment demonstrates the potential for sexual imprinting on dietary cues learned in utero and/or postnatally to facilitate reproductive isolation and potentially speciation.

Open Research Badges

This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at https://doi.org/10.5061/dryad.n1qq6v3.
Structural Studies, Antimicrobial Activity and Protein Interaction of Photostable Terpyridine Silver(I) Complexes
Authors: Mansour Ahmed M. , Radacki Krzysztof
Published: October 2019

Photostable mono‐ and binuclear silver(I) complexes derived from terpyridine ligands (4′‐(2‐pyridyl)‐2,2′:6′,2′′‐terpyridine (LPY) (1), 4′‐(4‐phenyl morpholine)‐2,2′:6′,2′′‐terpyridine (Lmorph) (2) and 1,4‐bis (2,2′:6′,2′′‐terpyridin‐4′yl) benzene (LDB) (3)) were synthesized and fully characterized in the solution and solid‐state including [1H–15N] heteronuclear multiple bond coherence (HMBC) NMR analysis and single‐crystal X‐ray analysis of five‐coordinates [Ag2(LPY)2(CH3CN)2](SO3CF3)2. Based on the NMR and ESI‐MS data, complex 1 exists as dimeric species, formed by head‐to‐tail interaction, while monomeric species of 3 predominantly exist in the same solvents. The protein binding affinity of 1–3 was investigated by using hen white egg lysozyme (HEWL). To explore where the metalation site of HEWL is, the interactions between the complexes and histidine were studied by NMR. The morpholine ligand and its Ag(I) complex (2) exhibited interesting antimicrobial activity. In comparison with AgOSO2CF3, compounds 1–3 displayed lower cytotoxicity to non‐malignant human embryonic kidney (HEK293) cells, and induced negligible haemoglobin release.
Human values and ideological beliefs as predictors of attitudes toward immigrants across 20 countries: The country‐level moderating role of threat
Authors: Araújo Rafaella de C. R. , Bobowik Magdalena , Vilar Roosevelt , Liu James H. , Gil de Zuñiga Homero , Kus‐Harbord Larissa , Lebedeva Nadezhda , Gouveia Valdiney V.
Published: October 2019

Immigration is a worldwide subject of interest, and studies about attitudes toward immigrants have been frequent due to immigration crises in different locations across the globe. We aimed at understanding individual‐level effects of human values and ideological beliefs (Right‐Wing Authoritarianism—RWA, and Social Dominance Orientation—SDO) on attitudes toward immigrants, and whether country‐level variables (perception of Islamic fundamentalism as a threat, perception of immigrants as a threat, and international migrant stock) moderate these relations. With representative samples from 20 countries (N = 21,362; the Americas, Europe, Asia, and Oceania), and using Multilevel Bayesian regressions, results showed the negative effect of RWA, SDO, and existence values on attitudes toward immigrants, and the positive effects of suprapersonal and interactive values. Cross‐level interactions indicated that the effects of RWA, SDO, and suprapersonal and existence values were intensified in countries with societally high levels of perceiving Islamic fundamentalism as a threat. International migrant stock served as a country‐level moderator for the effects of SDO and RWA only. When country‐level moderators were included simultaneously, Islamic fundamentalism as a threat was the most consistent moderator. Framing theory is offered as a plausible explanation of these results.
Modification of Gold Electrode via Electrografting of the in situ Generated 3‐Carboxy‐1,2,4‐triazoldiazonium Salt for Label‐free Determination of Carcinoembryonic Antigen
Authors: Svalova T. S. , Saigushkina A. A. , Medvedeva M. V. , Malysheva N. N. , Zhdanovskikh V. O. , Kozitsin I. V. , Kozitsina A. N.
Published: October 2019

In present study electrografting of the in situ generated 3‐carboxy‐1,2,4‐triazoldiazonium chloride on the Au disk electrode have been studied. The electrode film thickness differences between electrodeposited due to the aryl radical structure 3‐carboxy‐1,2,4‐triazoldiazonium chloride and 4‐carboxyphenyldiazonium salt was shown. The mechanism of 3‐carboxy‐1,2,4‐triazoldiazonium chloride electrografting has been proposed. 4‐nitroanilin was used to investigate the carbodiimide crosslinking capacity. It was established that electrodeposited films are suitable for carbodiimide crosslinking but the reaction proceed only on the “external” electrografted layer. Under the chosen optimal parameters, the label‐free electrochemical immunosensor have been developed. 3‐carboxy‐1,2,4‐triazoldiazonium chloride electrografting provided improvement of analytical characteristics in respect to electrodeposited 4‐carboxyphenyldiazonium salt. The linear range for carcinoembryonic antigen (CEA) detection is 10–104 ng ⋅ ml−1, the limit of detection estimated as 0.2 ng ⋅ ml−1. The developed immunosensor is stable during 30 day′s storage and selective against excess of bovine serum albumin as an interfering reagent.
Engineered disulfide bonds improve thermostability and activity of L‐isoleucine hydroxylase for efficient 4‐HIL production in Bacillus subtilis 168
Authors: Qiao Zhina , Xu Meijuan , Shao Minglong , Zhao Youxi , Long Mengfei , Yang Taowei , Zhang Xian , Yang Shangtian , Nakanishi Hideki , Rao Zhiming
Published: October 2019

4‐Hydroxyisoleucine, a promising drug, has mainly been applied in the clinical treatment of type 2 diabetes in the pharmaceutical industry. l‐Isoleucine hydroxylase specifically converts l‐Ile to 4‐hydroxyisoleucine. However, due to its poor thermostability, the industrial production of 4‐hydroxyisoleucine has been largely restricted. In the present study, the disulfide bond in l‐isoleucine hydroxylase protein was rationally designed to improve its thermostability to facilitate industrial application. The half‐life of variant T181C was 4.03 h at 50°C, 10.27‐fold the half‐life of wild type (0.39 h). The specific enzyme activity of mutant T181C was 2.42 ± 0.08 U/mg, which was 3.56‐fold the specific enzyme activity of wild type 0.68 ± 0.06 U/mg. In addition, molecular dynamics simulation was performed to determine the reason for the improvement of thermostability. Based on five repeated batches of whole‐cell biotransformation, Bacillus subtilis 168/pMA5‐idoT181C recombinant strain produced a cumulative yield of 856.91 mM (126.11 g/L) 4‐hydroxyisoleucine, which is the highest level of productivity reported based on a microbial process. The results could facilitate industrial scale production of 4‐hydroxyisoleucine. Rational design of disulfide bond improved l‐isoleucine hydroxylase thermostability and may be suitable for protein engineering of other hydroxylases.
Contribution of GO System Glycosylases to Mutation Prevention in Caulobacter crescentus
Authors: Fernández‐Silva Frank S. , Schulz Mariane L. , Alves Ingrid Reale , Freitas Rubia R. , da Rocha Raquel Paes , Lopes‐Kulishev Carina O. , Medeiros Marisa H. G. , Galhardo Rodrigo S.
Published: October 2019

8‐oxo‐7,8‐dihydroguanine, commonly referred to as 8‐oxoG, is considered one of the most predominant oxidative lesions formed in DNA. Due to its ability to pair with adenines in its syn configuration, this lesion has a strong mutagenic potential in both eukaryotes and prokaryotes. Escherichia coli cells are endowed with the GO system, which protects them from the mutagenic properties of this lesion when formed both in cellular DNA and the nucleotide pool. MutY and MutM (Fpg) DNA glycosylases are crucial components of the GO system. A strong mutator phenotype of the Escherichia coli mutM mutY double mutant underscores the importance of 8‐oxoG repair for genomic stability. Here, we report that in Caulobacter crescentus, a widely studied alpha‐proteobacterium with a GC‐rich genome, the combined lack of MutM and MutY glycosylases produces a more modest mutator phenotype when compared to E. coli. Genetic analysis indicates that other glycosylases and other repair pathways do not act synergistically with the GO system for spontaneous mutation prevention. We also show that there is not a statistically significant difference in the spontaneous levels 8‐oxodGuo in E. coli and C. crescentus, suggesting that other yet to be identified differences in repair or replication probably account for the differential importance of the GO system between these two species. Environ. Mol. Mutagen. 61:246–255, 2020. © 2019 Wiley Periodicals, Inc.
In vivo localization and postmortem stability of benzo[a]pyrene‐DNA adducts
Authors: Poirier Miriam C. , Beland Frederick A. , Divi Kathyayini V. , Damon Alyssa L. , Ali Mehnaz , Vanlandingham Michelle M. , Churchwell Mona I. , Von Tungeln Linda S. , Dwyer Jennifer E. , Divi Rao L. , Beauchamp Guy , Martineau Daniel
Published: October 2019

DNA adducts of carcinogenic polycyclic aromatic hydrocarbons (PAHs) play a critical role in the etiology of gastrointestinal tract cancers in humans and other species orally exposed to PAHs. Yet, the precise localization of PAH‐DNA adducts in the gastrointestinal tract, and the long‐term postmortem PAH‐DNA adduct stability are unknown. To address these issues, the following experiment was performed. Mice were injected intraperitoneally with the PAH carcinogen benzo[a]pyrene (BP) and euthanized at 24 h. Tissues were harvested either at euthanasia (0 time), or after 4, 8, 12, 24, 48, and 168 hr (7 days) of storage at 4°C. Portions of mouse tissues were formalin‐fixed, paraffin‐embedded, and immunohistochemically (IHC) evaluated by incubation with r7,t8‐dihydroxy‐t‐9,10‐epoxy‐7,8,9,10‐tetrahydrobenzo[a]pyrene (BPDE)‐DNA antiserum and H‐scoring. The remaining tissues were frozen, and DNA was extracted and assayed for the r7,t8,t9‐trihydroxy‐c‐10‐(N
2‐deoxyguanosyl)‐7,8,9,10‐tetrahydrobenzo[a]pyrene (BPdG) adduct using two quantitative assays, the BPDE‐DNA chemiluminescence immunoassay (CIA), and high‐performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC‐ES‐MS/MS). By IHC, which required intact nuclei, BPdG adducts were visualized in forestomach basal cells, which included gastric stem cells, for up to 7 days. In proximal small intestine villus epithelium BPdG adducts were visualized for up to 12 hr. By BPDE‐DNA CIA and HPLC‐ES‐MS/MS, both of which used DNA for analysis and correlated well (P= 0.0001), BPdG adducts were unchanged in small intestine, forestomach, and lung stored at 4°C for up to 7 days postmortem. In addition to localization of BPdG adducts, this study reveals the feasibility of examining PAH‐DNA adduct formation in wildlife species living in colder climates. Environ. Mol. Mutagen. 61:216–223, 2020. © 2019 Wiley Periodicals, Inc.
Reconstructing large‐scale karst paleogeomorphology at the top of the Ordovician in the Ordos Basin, China: Control on natural gas accumulation and paleogeographic implications
Authors: Xiao Di , Tan Xiucheng , Fan Liyong , Zhang Daofeng , Nie Wancai , Niu Tong , Cao Jian
Published: October 2019

Karstification in carbonate successions has an important influence on hydrocarbon accumulation. Taking the Ordos Basin, currently the largest petroliferous basin in China, as an example, this study examines the large‐scale, long‐term (~120 Myr) paleokarst at the top of the Ordovician. The objectives of the study are to characterize the karst paleogeomorphology of this area, to explain the inconsistency between existing understandings of karst paleogeomorphology and exploration in the eastern Ordos Basin, and to reveal the control of paleokarst on natural gas accumulation and its paleogeographic significance. A total of 860 exploration wells were used for detailed stratigraphic correlation and analysis, along with core observations, well‐logging analyses, physical property characterization, and isotope analyses. Results of residual thickness and moldic thickness reconstruction reveal variation in karst paleogeomorphology between north and south in the eastern Ordos Basin, differing from the traditionally recognized E‐W variation. Two geomorphic units are classified as follows: the karst highland and the karst slope from north to south, with the karst slope being subdivided into northern and southern slope areas. The karst highland area has negligible reservoir capacity and hydrocarbon accumulation owing to the enhanced denudation that occurred there. In contrast, the northern karst slope shows favorable reservoir properties and has abundant gas wells according to well‐logging interpretations, whereas the southern karst slope is of poor reservoir quality and hosts mainly water wells. Differences in dissolution‐filling effects controlled by the surface paleodrainage system are suggested to be the main contributor to differential reservoir space preservation, which, together with the variable width and depth of source rocks in the grooves (thereby variably exposing source rock), further promoted differential gas accumulation. The Ordos Basin and its periphery in the southwestern North China Craton (NCC) show inheritance of sedimentary‐tectonic patterns from the Middle Ordovician to the Late Carboniferous. These results should provide a reference for hydrocarbon exploration in the Ordovician of other basins in the NCC in which karst occurs and karst basins worldwide, and deepens understanding of the paleogeographic framework in the context of regional uplift of the North China Platform.
Effects of microwave blanching conditions on the quality of green asparagus (Asparagus officinalis L.) butt segment
Authors: Nguyen Thi Van Linh , Tran Thi Yen Nhi , Lam Duc Tri , Bach Long Giang , Nguyen Duy Chinh
Published: October 2019

Blanching is a pretreatment method that is often applied in fruit and vegetable processing to inhibit enzyme activity and reduce loss of food quality. It was recently discovered that well‐controlled microwave volumetric heating could improve the blanching efficiency and retain nutritional and sensorial values of product. This study was conducted to investigate effects of microwave blanching conditions on the quality of green asparagus (Asparagus officinalis L.) butt segments, a rich source of fiber and antioxidants but are often discarded during processing. The experiments were designed by one‐factor‐at‐a‐time method with two varying factors including blanching time (2, 4, 6, and 8 min) and microwave power output (150, 300, 450, and 600 W). Quality of product was evaluated by sensory, retention of phenolics, and free‐radical scavenging activity retention. The results showed that longer blanching time or higher microwave power was associated with reduced quality of green asparagus butt segment. Besides, the appropriate parameters for microwave blanching of the green asparagus butt segment was found at 300 W for 4 min.
Molecular simulation of equal density temperature in CCS under geological sequestration conditions
Authors: Yuan Lei , Zhang Yi , Zhao Jiafei , Song Yongchen , Chi Yuan
Published: October 2019

Storing carbon dioxide (CO2) in geological reservoirs, principally saline aquifers, is one of the main methods proposed to address the issue of anthropogenic CO2 emissions. With the aim of ensuring long‐term CO2 storage in geological reservoirs, the density of the CO2–brine solution is an important property that controls brine buoyancy. In this study, molecular dynamics simulations were performed to investigate the density of CO2–water solutions at temperatures in the range 60–240°C, pressures in the range 10–100 MPa, varying CO2 mass fractions (1%, 2%, and 3%), and varying CO2–NaCl–water solution salinities (2 and 4 mol/kg), all of which are crucial parameters for CO2 geological sequestration. The optimal combination model of CO2(TraPPE)–NaCl(OPLS)–water(TIP4P/2005) was determined by comparing experimental values with simulate density under geological conditions. The simulation results reproduced the trends of the experimental values. The equal density temperature (Te) indicated that solution density decreases upon CO2 dissolution in water when the temperature increases to a certain point. According to the simulation results, Te increases with increasing pressure and decreases with increasing salinity. Further, the results of analysis of the structural properties of the solution to determine the causes of Te showed that, with increasing temperature, the distance between CO2 molecules and adjacent atoms increases significantly, which reduces the local density around the CO2 molecules. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Upgrading without formal integration in M&A: The role of social integration
Authors: Torres de Oliveira Rui , Sahasranamam Sreevas , Figueira Sandra , Paul Justin
Published: October 2019

Research summary

By adopting a phenomenon‐based research approach, we examine the case of an emerging market (EM) supplier upgrading its position in the automotive global value chain (GVC) through the acquisition of a technologically advanced firm from a developed market (DM). Drawing on GVC and social integration literature, we explore the role of social integration adopted by the EM acquirer to achieve upgrading through acquisition. We develop a conceptual framework where we explain the different social integration mechanisms that EM multinationals employ before and after acquisitions to achieve upgrading.

Managerial summary

When analyzing an EM firm acquiring a DM firm we found that social integration is a key factor that enables knowledge transfer, particularly if no formal or structural integration occurs. This suggests that the development of mechanisms to facilitate strong socially integrated relationships with acquired firms is central for such type of acquisitions. Our research shows that EM firm managers need to put in place combinations of social integration mechanisms during different phases of the acquisition. Environmental and cognitive social integration mechanisms are crucial for gaining initial legitimacy. Furthermore, affective social integration is important for initiating process and functional upgrading, while cognitive social integration mechanisms become important for initiating intersectorial upgrading.
Potential of on‐scalp MEG: Robust detection of human visual gamma‐band responses
Authors: Iivanainen Joonas , Zetter Rasmus , Parkkonen Lauri
Published: October 2019

Electrophysiological signals recorded intracranially show rich frequency content spanning from near‐DC to hundreds of hertz. Noninvasive electromagnetic signals measured with electroencephalography (EEG) or magnetoencephalography (MEG) typically contain less signal power in high frequencies than invasive recordings. Particularly, noninvasive detection of gamma‐band activity (>30 Hz) is challenging since coherently active source areas are small at such frequencies and the available imaging methods have limited spatial resolution. Compared to EEG and conventional SQUID‐based MEG, on‐scalp MEG should provide substantially improved spatial resolution, making it an attractive method for detecting gamma‐band activity. Using an on‐scalp array comprised of eight optically pumped magnetometers (OPMs) and a conventional whole‐head SQUID array, we measured responses to a dynamic visual stimulus known to elicit strong gamma‐band responses. OPMs had substantially higher signal power than SQUIDs, and had a slightly larger relative gamma‐power increase over the baseline. With only eight OPMs, we could obtain gamma‐activity source estimates comparable to those of SQUIDs at the group level. Our results show the feasibility of OPMs to measure gamma‐band activity. To further facilitate the noninvasive detection of gamma‐band activity, the on‐scalp OPM arrays should be optimized with respect to sensor noise, the number of sensors and intersensor spacing.
Novel immune‐modulating drugs for advanced head and neck cancer
Authors: Chen Tien‐Hua , Chang Peter M. ‐H. , Yang Muh‐Hwa
Published: October 2019

Background

Recently, two anti‐PD‐1 immune checkpoint inhibitors, pembrolizumab and nivolumab, have been approved by the US Food and Drug Administration for patients who fail on platinum‐based chemotherapy. However, overall response and progression‐free survival are still limited, and multiple novel agents are under development to fulfill this unmet clinical need.

Methods

Publications between 1992 and 2019 regarding the immunological/biological mechanisms and early phase clinical trial outcomes of immunomodulatory agents for head and neck cancer were described in this review article.

Results

Eleven immunomodulatory agents for advanced head and neck, including small molecules, antibodies, and therapeutic vaccines were described. Treatment responses were noted in nearly all 11 agents, as monotherapy or combination therapy.

Conclusions

Potentials of the novel immunomodulatory agents to improve treatment efficacy of head and neck cancer and to maintain tolerable safety profile have been disclosed.
Effects of infant negative affect and contextual factors on infant regulatory capacity: The moderating role of infant sex
Authors: Petrenko Anton , Kanya Meghan J. , Rosinski Leanna , McKay Erin R. , Bridgett David J.
Published: October 2019

Infants' abilities to orient and regulate are directly linked to self‐regulatory capacity in childhood, which is subsequently associated with indicators of health and well‐being. However, relatively little is known regarding factors affecting early orienting and regulation. The current study evaluated the effects of infant negative affect and household chaos when children were 4 months old and parenting at 6 months of age on subsequent regulatory capacity at 8 months of age in a sample of 179 mother‐infant dyads. The potential moderating role of infant sex was examined in consideration of the viability–vulnerability tradeoff theory, which posits that females may be more susceptible to the impact of stressful environments in early development. Analyses indicated that early household chaos was related to subsequently lower orienting/regulatory abilities at 8 months of age. Additionally, there were significant sex‐by‐negative affectivity and sex‐by‐household chaos interactions, such that boys' regulatory capacity was negatively impacted by early negative affectivity and girls' was adversely affected by household chaos. Findings indicate some support for the viability–vulnerability tradeoff theory.

Highlights

The current study evaluated whether early negative affect and contextual factors impacted infant orienting/regulation at 8 months of age, and whether they influenced boys and girls differently.

Results indicate that chaotic household environments negatively impact infants' ability to orient/regulate, and that male and female infants are differently affected by early negative affectivity and household chaos.

This study suggests that parents should aim to decrease levels of home chaos to promote optimal regulatory development, and finds some support for the viability‐vulnerability tradeoff theory.
An updated single center experience with plerixafor and granulocyte colony‐stimulating factor for stem cell mobilization in light chain amyloidosis
Authors: Badar Talha , Dhakal Binod , Szabo Aniko , Padmanabhan Anand , Johnson Bryon D. , Heidtke Sarah , Esselmann Jean , Chhabra Saurabh , Hamadani Mehdi , Hari Parameswaran , D'Souza Anita
Published: October 2019

The use of granulocyte‐colony stimulating factor (G‐CSF) with or without chemotherapy to mobilize hematopoietic progenitor cells (HPCs) can result in significant morbidity in light chain (AL) amyloidosis patients. Plerixafor, a strong inducer and mobilizer of HPCs, can be used as an adjunct to G‐CSF to improve mobilization efficiency. We describe the outcomes for combined G‐CSF/plerixafor mobilized patients with AL amyloidosis. We reviewed data of 53 consecutive AL amyloidosis patients who underwent combined G‐CSF/plerixafor HPC mobilization between May 2011 and October 2017 at our institution. We evaluated patients for HPC collection efficiency, perimobilization toxicity and postautologous hematopoietic cell transplantation (autoHCT) outcomes. Median CD34+ cell collection was 12.4 × 106 cells/kg (range 2.5 × 106 to 34.1 × 106 cells/kg) and 45 (85%) patients had collections of ≥5.0 × 106 CD34+ cells/kg. There were no mobilization failures or perimobilization mortality. During mobilization, 37 (70%) patients had weight gain (median 1.3 kg, range 0.1‐4) but none >10% body weight, 5 (10%) patients had diarrhea, and one patient each had hypotension and cardiac arrhythmia. Among the 31 patients analyzed for CD34 collection efficiency (CE), the median CD34 CE was 47% (range 36‐62). At 5 years follow‐up 82% and 84% of patients were progression‐free and alive, respectively. Our results suggest that G‐CSF/plerixafor mobilization is safe, well tolerated, and effective in AL amyloidosis.
Mechanism and Stereoselectivity of the Elementometalation Process of Activated Alkyne RCCR(RCO2Me) by Cp2TaH3
Authors: Wang Jia , Li Xiaoyan , Zheng Shijun , Meng Lingpeng
Published: October 2019

The elementometalation process is a fundamental chemical step in several catalytic cycles. In this work, density functional theory computations have elucidated the detailed elementometalation mechanism of activated alkyne RCCR(RCO2Me) by Cp2TaH3and rationalized the selectivity in experimental findings. The calculated results show that in the formation process of (E)‐olefin monohydride((E)‐Pro), the Gibbs free energy barrier is low and the entire reaction is spontaneous and exothermic; thus, (E)‐Pro can be formed easily. The formation of (Z)‐η2‐olefin monohydride complex ((Z)‐Pro) is difficult due to its high Gibbs free energy barrier. The formation process (E)‐Pro consists of the following five steps: hydride H1‐shift, conformational isomerism 1, hydride H2‐shift, conformational isomerism 2, and olefin coordination process. Topological analysis shows that there is a five‐membered ring plane structure in the reaction pathway and that the final product (E)‐Pro belongs to a typicalη2‐olefin monohydride complex. Our calculated results provide an explanation for experimental observations and useful insights for further development of olefin functionalization. © 2019 Wiley Periodicals, Inc.
TITAN: A Code for Modeling and Generating Electric Fields—Features and Applications to Enzymatic Reactivity
Authors: Stuyver Thijs , Huang Jing , Mallick Dibyendu , Danovich David , Shaik Sason
Published: October 2019

We present here a versatile computational code named “elecTric fIeld generaTion And maNipulation (TITAN),” capable of generating various types of external electric fields, as well as quantifying the local (or intrinsic) electric fields present in proteins and other biological systems according to Coulomb's Law. The generated electric fields can be coupled with quantum mechanics (QM), molecular mechanics (MM), QM/MM, and molecular dynamics calculations in most available software packages. The capabilities of the TITAN code are illustrated throughout the text with the help of examples. We end by presenting an application, in which the effects of the local electric field on the hydrogen transfer reaction in cytochrome P450 OleTJE enzyme and the modifications induced by the application of an oriented external electric field are examined. We find that the protein matrix in P450 OleTJE acts as a moderate catalyst and that orienting an external electric field along the Fe─O bond of compound I has the biggest impact on the reaction barrier. The induced catalysis/inhibition correlates with the calculated spin density on the O‐atom. © 2019 Wiley Periodicals, Inc.
Systematic Interaction Analysis of Anti‐Human Immunodeficiency Virus Type‐1 Neutralizing Antibodies with High Mannose Glycans Using Fragment Molecular Orbital and Molecular Dynamics Methods
Authors: Kusumoto Miyu , Ueno‐Noto Kaori , Takano Keiko
Published: October 2019

A series of broadly neutralizing antibodies called PGT have been shown to be bound directly to human immunodeficiency virus type‐1 via high mannose glycans on glycoprotein gp120. Despite the sequence similarities of amino acids of the antibodies, their affinities to the glycan differ. Glycan–antibody interactions among these antibodies are systematically compared with quantum chemical fragment molecular orbital calculations and molecular dynamics simulations. The differences among structural stability of the glycan in the active site of the complexes and total interaction energies as well as binding free energies between the glycan and antibodies agree well with the experimentally shown affinities of the glycan to the antibodies. The terminal saccharide, Man D3, is structurally stable and responsible for the glycan–antibody binding through electrostatic and dispersion interactions. The structural stability of nonterminal saccharides such as Man 4 or Man C plays substantial roles in the interaction via direct hydrogen bonds. © 2019 Wiley Periodicals, Inc.
A proof‐of‐concept study on the effects of low total cfDNA content and solutions to increase the NIPT trisomy 21 detection rate
Authors: Du Yang , Chen Ailing , Yang Rui , Zhou Tao , Zhou Qin , Yang Lan , Wang Juan , Hong Yan , Chen Chen , Wan Qian , Yang Lin , Chen Ying
Published: October 2019

Background

Non‐invasive prenatal testing (NIPT) is routinely used in clinical practice for fetal trisomy screening, but low total cfDNA content and low fetal fraction (LFF) are two factors that affect the detection rate. Samples with low total cfDNA or LFF usually end up with “no‐call” results, followed by the blood redraw and re‐testing, which is inconvenient for pregnant women and clinicians.

Methods

We created mock trisomy 21 (T21) samples to investigate the effects of low total cfDNA with low LFF and possible solutions to increase their detection rate.

Results

Samples with low total cfDNA resulted in the decreased unique reads number and increased duplication rate. Abnormal correlations between library concentration and raw reads number and the coverage fluctuation value, ZsdNorm, were also discovered, suggesting that low total cfDNA could lead to the overestimation of the library concentration. Additionally, a non‐reference‐based derivative value method (DV method) was evaluated and the data demonstrated that the detection sensitivity of trisomy 21 was increased from 33.33% (6/18) to 94.44% (17/18) in samples with 5% fetal fraction comparing with the z‐score approach, whereas for LFF (3.5%) group, the performance was raised from 0% to 35.29% (6/17).

Conclusion

Low total cfDNA has significant impacts on NIPT performance by altering sequencing quality. The non‐reference‐based DV method could increase the T21 detection rate in samples with limited cfDNA content and 5% fetal fraction, but it was not as effective for those with LFF.
Attachment and social support in romantic dyads: A systematic review
Authors: McLeod Saul , Berry Katherine , Hodgson Catherine , Wearden Alison
Published: October 2019

Objective

Taking a dyadic perspective, this systematic review examined the relationship between attachment constructs and differences in support behavior in romantic couples.

Method

Four databases were searched including PsychINFO, Embase, OVOID MEDLINE, and AMED. Out of 2,401 unique references, 43 met the study inclusion criteria.

Results

The review findings offer validation for an attachment‐based model of support processes in couples. Maladaptive support behaviors were more likely to occur when one or both members of a romantic dyad had an insecure attachment. Individuals with an avoidant or anxious attachment were more likely to provide poor quality support, and when receiving support, to interpret it in a negative manner.

Conclusion

We recommend therapeutic interventions to help individuals with insecure attachments to follow more adaptive ways of support seeking, so social relationships are more able to offer a buffering effect against the development of mental health problems.
Long noncoding RNA MIAT2 alleviates lipopolysaccharide‐induced inflammatory damage in WI‐38 cells by sponging microRNA‐15
Authors: Zhang Hong , Zhao Jing , Shao Peng
Published: October 2019

Neonatal pneumonia is a high neonatal mortality disease. We studied the function and mechanism of long noncoding RNA myocardial infarction‐associated transcript 2 (lncRNA MIAT2) on lipopolysaccharide (LPS)‐induced inflammation in WI‐38 cells. Cell Counting Kit‐8 and apoptosis assay were respectively used to detect the functions of LPS, MIAT2, and microRNA‐15 (miR‐15) on viability and apoptosis. MIAT2 and miR‐15 expressions were changed by cell transfection. Moreover, reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR), western blot, and enzyme‐linked immunosorbent assay were used to detect the expressions of interleukin (IL)‐6 and monocyte chemoattractant protein‐1 (MCP‐1). The levels of Bax, cleaved‐caspase‐3, and cell pathways‐related proteins were tested by western blot. Besides, the levels of miR‐15 and MIAT2 were tested by RT‐qPCR. We found that LPS declined cell viability and heightened apoptosis and levels of Bax, cleaved‐caspase‐3, IL‐6, and MCP‐1. MIAT2 was negatively regulated by LPS and it alleviated LPS‐induced damage. Furthermore, MIAT2 reversely regulated miR‐15 and miR‐15 mimic could reverse the effects of MIAT2. Finally, MIAT2 restrained the p38MAPK and NF‐κB pathways by downregulating miR‐15. In conclusion, MIAT2 alleviated LPS‐induced inflammation damage in WI‐38 cells by sponging miR‐15 via p38MAPK and NF‐κB pathways.
β-Catenin stabilization in NOD dendritic cells increases IL-12 production and subsequent induction of IFN-γ-producing T cells
Authors: Zirnheld Arin L , Villard Marine , Harrison Alisha M , Kosiewicz Michele M , Alard Pascale
Published: October 2019

Dendritic cells (DC) from diabetes-prone NOD mice and patients with type 1 diabetes (T1D) produce excess IL-12 that drives development of β-cell-destroying IFN-γ-producing T cells. The molecular mechanisms that control IL-12 production in T1D are unclear. In this study, we report that β-catenin, a multifunctional protein involved in inflammation, is dramatically increased in DC from NOD mice. We further investigated the mechanisms leading to accumulation of β-catenin in NOD DC and its role in the inflammatory pathogenic responses associated with T1D. Hyperphosphorylation of β-catenin at a stabilizing residue, serine 552, mediated by activation of Akt, appears to lead to β-catenin accumulation in NOD DC. Elevated β-catenin in DC correlated with IL-12 production and induction of IFN-γ-producing CD4 cells. On the one hand, knockdown/inhibition of β-catenin significantly reduced NOD DC production of IL-12 and their ability to induce IFN-γ-producing CD4 cells. On the other hand, overexpression of β-catenin in control DC resulted in increased IL-12 production and induction of IFN-γ-production in T cells. Additionally, we found that β-catenin inhibitors decreased NF-κB activation in NOD DC and IFN-γ production by NOD T cells in vivo. These data strongly suggest that accumulation of β-catenin in DC from NOD mice drives IL-12 production, and consequently, development of pathogenic IFN-γ-producing T cells. Targeting the defect responsible for β-catenin accumulation and subsequent overproduction of pro-inflammatory cytokines by NOD DC could be an effective therapeutic strategy for the prevention and/or treatment of T1D.
A mutation in mannose‐phosphate‐dolichol utilization defect 1 reveals clinical symptoms of congenital disorders of glycosylation type I and dystroglycanopathy
Authors: van Tol Walinka , Ashikov Angel , Korsch Eckhard , Abu Bakar Nurulamin , Willemsen Michèl A. , Thiel Christian , Lefeber Dirk J.
Published: October 2019

Congenital disorders of glycosylation type I (CDG‐I) are inborn errors of metabolism, generally characterized by multisystem clinical manifestations, including developmental delay, hepatopathy, hypotonia, and skin, skeletal, and neurological abnormalities. Among others, dolichol‐phosphate‐mannose (DPM) is the mannose donor for N‐glycosylation as well as O‐mannosylation. DOLK‐CDG, DPM1‐CDG, DPM2‐CDG, and DPM3‐CDG are defects in the DPM synthesis showing both CDG‐I abnormalities and reduced O‐mannosylation of alpha‐dystroglycan (αDG), which leads to muscular dystrophy‐dystroglycanopathy. Mannose‐phosphate‐dolichol utilization defect 1 (MPDU1) plays a role in the utilization of DPM. Here, we report two MPDU1‐CDG patients without skin involvement, but with massive dilatation of the biliary duct system and dystroglycanopathy characteristics including hypotonia, elevated creatine kinase, dilated cardiomyopathy, buphthalmos, and congenital glaucoma. Biochemical analyses revealed elevated disialotransferrin in serum, and analyses in fibroblasts showed shortened lipid linked oligosaccharides and DPM, and reduced O‐mannosylation of αDG. Thus, MPDU1‐CDG can be added to the list of disorders with overlapping biochemical and clinical abnormalities of CDG‐I and dystroglycanopathy.

Synopsis

Mannose‐phosphate‐dolichol utilization defect 1 patients can have overlapping biochemical and clinical abnormalities of congenital disorders of glycosylation type I and dystroglycanopathy.