bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classifying molecular phenotypes of G6PC variants for pathogenic properties and to guide therapeutic development
Authors: Plona Kathleen L. , Eastman Jean F. , Drumm Mitchell L. 
Published: March 2021

AbstractDue to advances in sequencing technologies, identification of genetic variants is rapid. However, the functional consequences of most genomic variants remain unknown. Consequently, variants of uncertain significance (VUS) that appear in clinical DNA diagnostic reports lack sufficient data for interpretation. Algorithms exist to aid prediction of a variant's likelihood of pathogenicity, but these predictions usually lack empiric evidence. To examine the feasibility of generating functional evidence in vitro for a given variant's role in disease, a panel of 29 coding sequence variants in the G6PC gene was assessed. G6PC encodes glucose‐6 phosphatase enzyme, and reduction in its function causes the rare metabolic disease glycogen storage disease type 1a (GSD1a). Variants were heterologously expressed as fusion proteins in a hepatocyte‐derived cell line and examined for effects on steady‐state protein levels, biosynthetic processing, and intracellular distribution. The screen revealed variant effects on protein levels, N‐linked glycosylation status, and cellular distribution. Of the eight VUS tested, seven behaved similar to wild‐type protein while one VUS, p.Cys109Tyr, exhibited features consistent with pathogenicity for all molecular phenotypes assayed, including significantly reduced protein levels, alteration in protein glycosylation status, and abnormally diffuse protein localization pattern, and has recently been reported in a patient with GSD1a. Our results show that such a screen can add empiric evidence to existing databases to aid in diagnostics, and also provides further classification for molecular phenotypes that could be used in future therapeutic screening approaches for small molecule or gene editing strategies directed at specific variants.
Discovery and validation of quality markers of Fructus Aurantii against acetylcholinesterase using metabolomics and bioactivity assays
Authors: Wang Yi‐Kun , Zhou Zi‐Meng , Dai Man‐Yun , Ma Xiao‐Fang , Xiao Xue‐Rong , Zhang Shou‐Wen , Liu Hong‐Ning , Li Fei 
Published: March 2021

AbstractFructus Aurantii is a traditional medicated diet in East Asia. To determine the underlying chemical markers responsible for the quality and efficacy of Fructus Aurantii, a sensitive metabolomic method was applied to distinguish Fructus Aurantii in Jiangxi Province from other two geographical locations (Hunan Province and Chongqing City) in China. In the present study, multivariate analyses were adopted to compare chemical compositions in 21 batches of Fructus Aurantii samples. Among three geographical origins, 23 differential compounds were structurally identified. Serum pharmacochemistry exhibited that 22 components could be detected in rat serum. Six differential and absorbed components were selected as six potential markers. Statistical analysis revealed that the content of six markers varied widely in three origins of Fructus Aurantii. Six differential and absorbed components were evaluated further by biological activity. Neohesperidin, naringin, and meranzin showed inhibitory effect on acetylcholinesterase that regulates gastrointestinal motility in vitro and in silico, suggesting that these three components may be determined as the active biomarkers of Fructus Aurantii. These findings demonstrate the potential of biomarkers for identification and quality control of Fructus Aurantii.
The role of root‐associated microbes in growth stimulation of plants under saline conditions
Authors: Liu Han‐Qing , Lu Xiang‐Bin , Li Zi‐Han , Tian Chang‐Yan , Song Jie 
Published: March 2021

AbstractSoil salinization has adverse effects on plant growth due to direct ion toxicity or secondary damage, such as mineral nutrition imbalance and the water stress caused by low osmotic potential. The rhizosphere processes of plants are likely to play an important role in the biological improvement of saline soil. However, the understanding of this remains limited. This review summarizes the progress made recently in exploring the effects of root‐associated microbes especially from halophytic species on the growth stimulation of plants under salinity. For example, halophytes attract and absorb beneficial rhizosphere growth‐promoting bacteria by producing rhizosphere exudates such as organic acids and enzymes, which is conducive to plant growth under salt stress. The plant growth‐promoting exogenous rhizobacteria (PGPR), attached to the roots of halophytes, can promote the growth of plants mainly through the improved absorption of nutrients by the host plants or through producing plant growth regulators. In addition, the colonization of endophytes can regulate plant ion balance and produce secondary metabolites such as growth‐promoting hormone and extracellular enzymes, activating antioxidant systems, and inducing plant system resistance against pathogenic microorganisms, thus promoting the growth of plants under salt stress. The inoculation of arbuscular mycorrhizal fungi (AMF) under salt stress can facilitate plants to change the ion balance or obtain water from the soil, and that the formation of other hyphae may promote the transfer of water and nutrients to plants. Therefore, understanding the effects of root‐associated microbes on the growth stimulation of plants under salinity is of great significance to improving their salt tolerance, so as to improve saline‐alkali land for the construction of a more effective biological improvement model.
Comparison of 1064‐nm and Dual‐Wavelength (532/1064‐nm) Picosecond‐Domain Nd:YAG Lasers in the Treatment of Facial Photoaging: A Randomized Controlled Split‐Face Study
Authors: Zhang Mengli , Huang Yuqing , Wu Qiuju , Lin Tong , Gong Xiangdong , Chen Hao , Wang Yan 
Published: March 2021

Background and ObjectivesTo compare the efficacy and safety of 1064‐nm and dual‐wavelength (532/1064 nm) picosecond Nd:YAG lasers with a holographic optic in the treatment of facial photoaging.Study Design/Materials and MethodsIn this prospective, randomized split‐face study, each half of each participant′s face was randomly treated with a 1064‐nm or 532/1064‐nm picosecond laser. All participants underwent five treatment sessions and follow‐up visits 1 and 3 months after the final treatment. The primary outcomes were measured as the global photoaging scores, determined by two physicians who were blinded to the treatments. The secondary outcomes were the participant‐assessed Global Aesthetic Improvement Scale (GAIS) and satisfaction scores. Histopathological examinations were performed.ResultsGlobal photoaging scores decreased significantly after treatment with either laser. The global photoaging scores, GAIS scores, and satisfaction scores did not differ significantly between the 1064‐nm and 532/1064‐nm picosecond laser treatments. Histological changes were similar between the two groups. Intraepidermal vacuoles and dermal hemorrhaging were observed immediately and 24 h after treatment. After five treatments, neocollagenesis was observed in the upper dermis of both groups, and elastic fibers were more elongated and orderly.ConclusionsTreatments with 1064‐nm and 532/1064‐nm picosecond Nd:YAG lasers were comparably effective at improving photodamaged facial skin by remodeling the collagen and elastin network through laser‐induced optical degradation and vascular damage.
Revisions to the IASP definition of pain—What does this mean for children?
Authors: Stevens Bonnie 
Published: March 2021

AbstractThe complexity of the phenomenon of pain defies a simple and straightforward definition. Acute, chronic, nociplastic and neuropathic pain account for multiple pathologic mechanisms and forms of expression. Pain varies widely in intensity, duration and nature, often complicating description for those who are experiencing the pain and/ or those who are observing it. Assessment of pain in children can be challenging, especially in those who may be incapable of self‐report report due to development immaturity or disability. In these children the responsibility of assessing pain often falls to the professional or lay care provider, whose knowledge, expertise and beliefs influence their judgements. The experience of pain includes not only the physiologic and behavioural indicators most frequently included in pain assessment measures but also encompasses the social and cognitive components that often go unrecognized. The 1979 IASP definition of pain has been praised for its brevity, simplicity and attention to the multidimensional nature of the phenomenon. It has also been criticized for ignoring mind‐body interactions, disempowering and neglecting vulnerable populations, paying little attention to ethical dimensions, and excluding cognitive and social factors that are integral to the experience of pain. After four decades, the 1979 definition of pain and the accompanying notes were evaluated and revised by a 14‐member IASP presidential task force with representation from basic and clinical research, geographical location and populations served (Pain, 2020, 161, 1976). These revisions resulted in decreasing the emphasis of pain associated with tissue damage in the definition, and, by removing the word ‘described’, allowing those who were nonverbal to be assessed using other validated pain indicators. Important revisions were also made to the Notes. The revisions that are most relevant for pain in children are discussed.
Characterization of the Detonation Pressure of a PETN Based PBX with the Optical Active Method
Authors: Quaresma Joana , Deimling Lukas , Campos Jose , Mendes Ricardo 
Published: March 2021

AbstractDetonation metrology is essential for the development of energetic materials, to characterize existing explosives, and to characterize materials behavior under high pressures. The optical active method (OAM), based on PMMA optical fibers (250 μm diameter) and their radiation transmission loss when shocked, was used to characterize the detonation wave (DW) and shock wave (SW) in inert barriers and applied to measure the detonation pressure in condensed explosives. The detonation velocity and detonation pressure of a PBX based on PETN (86 % PETN, 14 % Sylgard), known as Seismoplast were measured. The OAM with protected optical probes (POP) was used to determine the mean detonation velocity (7337 m s−1), whereas the OAM with bare optical probes (BOP) was used to measure the induced shock velocities generated by Seismoplast on different thicknesses of PMMA (1–9 mm), aluminum and copper (1–7 mm). Based on the shock velocities at the interfaces between the explosive and the inert barriers, the CJ pressure of Seismoplast was determined as 21.2 GPa.
Influences of Bu‐NENA and BDNPA/F Plasticizers on the Properties of Binder for High‐Energy NEPE Propellants
Authors: Wang Yalun , Rong Hui , Zhang Xiuhui , Chen Yu , Luo Wen , Liu Yunfei , Yao Weishang , Tian Ye 
Published: March 2021

AbstractDesensitized energetic plasticizer (DEP) plays a crucial role in the properties of the binder, and thus can further influence the performances of desensitive Nitrate Ester Plasticized Polyether (NEPE) propellants, which represents the development direction of the next generation solid propellant composites. However, at present, a study on influencing mechanisms for curing properties of propellant binders at the atomic and molecular level was rarely reported. In the current study, based on the curing kinetics and mechanical properties of PET/N‐100 binder, the influencing mechanism of the DEPs, BDNPA/F, and Bu‐NENA, on the binder was determined by the Gaussian quantum chemical calculation and MD simulation at the chemical bond and polymer chain levels, as well as the characterizations of the curing network structure, glass transition temperature, and microphase separation of the binder system. The consistent results at both micro and macro levels offer important theoretical guidance for studying the structure‐mechanism‐performance relationship of propellant binder, as well as for exploring the strategies that can reveal the curing mechanism of the binder system in depth.
Insights into the mechanisms of light‐oxygen‐voltage domain color tuning from a set of high‐resolution X‐ray structures
Authors: Remeeva Alina , Nazarenko Vera V. , Kovalev Kirill , Goncharov Ivan M. , Yudenko Anna , Astashkin Roman , Gordeliy Valentin , Gushchin Ivan 
Published: March 2021

AbstractLight‐oxygen‐voltage (LOV) domains are widespread photosensory modules that can be used in fluorescence microscopy, optogenetics and controlled production of reactive oxygen species. All of the currently known LOV domains have absorption maxima in the range of ~440 to ~450 nm, and it is not clear whether they can be shifted significantly using mutations. Here, we have generated a panel of LOV domain variants by mutating the key chromophore‐proximal glutamine aminoacid of a thermostable flavin based fluorescent protein CagFbFP (Gln148) to asparagine, aspartate, glutamate, histidine, lysine and arginine. Absorption spectra of all of the mutants are blue‐shifted, with the maximal shift of 8 nm observed for the Q148H variant. While CagFbFP and its Q148N/D/E variants are not sensitive to pH, Q148H/K/R reveal a moderate red shift induced byacidic pH. To gain further insight, we determined high resolution crystal structures of all of the mutants studied at the resolutions from 1.07 Å for Q148D to 1.63 Å for Q148R. Whereas in some of the variants, the aminoacid 148 remains in the vicinity of the flavin, in Q148K, Q148R and partially Q148D, the C‐terminus of the protein unlatches and the side chain of the residue 148 is reoriented away from the chromophore. Our results explain the absence of color shifts from replacing Gln148 with charged aminoacids and pave the way for rational design of color‐shifted flavin based fluorescent proteins.
Research on interference avoidance effect of OneWeb satellite constellation's progressive pitch strategy
Authors: Li Ting , Jin Jin , Li Wei , Ren Zixuan , Kuang Linling 
Published: March 2021

SummaryDue to the scarcity of spectrum resources, the non‐geostationary orbit (NGSO) satellite constellations, which have achieved rapid development in recent years, have to deal with the challenge of spectral coexistence with geostationary orbit (GSO) satellite systems. OneWeb has put forward the “progressive pitch” strategy for GSO networks protection; however, the technical details are not exposed. Herein, we propose a method to obtain the exact progressive pitch parameters suitable for OneWeb system in terms of the technical route of this strategy. Constrained by GSO satellite system's interference protection criterion, an optimization problem is formulated by mathematical modeling of the spectral coexistence scenario between OneWeb system and a GSO satellite system. This optimization problem is resolved by a set of transformations, and the progressive pitch parameters with less loss of the system service capability are obtained. In addition, numerical simulation results verify the effectiveness of the progressive pitch strategy with our obtained parameters for interference avoidance in most parts of the world, but service blind areas of OneWeb system may appear in some time. Finally, we briefly analyze the causes and elimination ways of the blind areas.
Receiving Care Through Digital Health Technologies: Drivers and Implications of Old-Age Digital Health Exclusion
Authors: Poli Arianna , Kostakis Ioannis , Barbabella Francesco 
Published: March 2021

AbstractThe transition from traditional to progressively digitised health systems is leading to new forms of care including, for instance, telehealth and mobile health (mHealth) solutions. On the one hand, such solutions hold the potential for allowing easier, quicker and remote access to health care. On the other hand, digital health technologies can set new challenges for older people, especially for those who are not familiar with such technologies, in terms of receiving the care they need through good access and level of use of services. Furthermore, these services do not necessarily reflect everyone’s preferences and needs. This chapter aims to conceptualise and systematically discuss old-age digital health exclusion. First, we highlight key structural, environmental, individual and socio-technical drivers of the non-use and low-use of digital technologies, considering also the aspect of agency and personal preferences. Second, we point out the main individual and societal implications of old-age digital health exclusion. Third, we provide a conceptual framework for old-age digital health exclusion which includes older people, drivers and implications. Finally, we offer some reflections about digital health technologies in health care, highlighting related issues, risks and challenges for ageing societies.
Introduction: Framing Civic Exclusion
Authors: Torres Sandra 
Published: March 2021

AbstractThe topic of old-age social exclusion has received increased attention as studies that measure the prevalence of this multidimensional phenomenon have shown its spread across countries; see Ogg (2005) who focuses on Europe, Hrast et al. (2013) who considers Central and Eastern Europe, and Macleod et al. (2019) who measure exclusion in the UK. The three chapters that belong to this section pay specific attention to two of the domains which Walsh et al. (2017) refer to as civic participation and socio-cultural aspects in their framework on exclusion in later life. In this book, we refer to them as civic exclusion [see Walsh et al. this volume]. It is worth noting that this domain has received the least scholarly attention so far within the literature (van Regenmortel et al. 2016; Walsh et al. 2017), even though there is clear evidence that civic engagement and socio-cultural aspects of exclusion can have an impact on self-rated health (Poortinga 2006). Thus, the purpose of the chapter is to offer an abridged introduction to the topic of civic exclusion in later life in order to offer context to the three chapters in this section.
Unemployment at 50+: Economic and Psychosocial Consequences
Authors: Murdock Elke , Filbig Marceline , Borges Neves Rita 
Published: March 2021

AbstractThroughout the lifespan, unemployment has severe consequences in terms of economic exclusion, and overall social exclusion, but is compounded in older age. Within the EU, a growing number of older adults (50+) are affected by joblessness. Job loss at a later stage in a professional career may determine an early and permanent exit from the labour market with significant psychosocial consequences. Herein lies the age-specific risk for older unemployed adults: once becoming unemployed they are at greater risk at staying unemployed. As a result, older unemployed people may face income cuts, deprivation of a central adulthood role and their mental and physical health may suffer. In this chapter, we draw attention to the latent functions of work, and the psychosocial consequences of job loss in later life. Applying a life-course perspective, the aim of this chapter is to explore how job loss can be framed as a form of acute economic exclusion, and how this exclusion can have significant implications for poor mental health. In a context of rising retirement ages, and the lack of preparedness of the labour market to deal with an ageing workforce, it is essential to understand these dynamics to guide policy development.
Coping Mechanisms of Divorced and Widowed Older Women to Mitigate Economic Exclusion: A Qualitative Study in Turkey and Serbia
Authors: Barlin Hande , Vojvodic Katarina , Mercan Murat Anil , Milicevic-Kalasic Aleksandra 
Published: March 2021

AbstractMany old adults are faced with the risk of social exclusion, which inhibits them from enjoying a satisfactory quality of life. Accordingly, understanding this multidimensional and multifaceted complex phenomena is crucial for building an inclusive society. Hence, studies concentrating on vulnerable groups with higher probability of economic forms of exclusion, such as widowed or divorced materially deprived women, are valuable as exclusion necessitates different actions for different segments of the older population. Against this background, this chapter investigates resilience and coping mechanisms of materially deprived widowed and separated/divorced older women. Data is taken from a qualitative study in Turkey and Serbia, two EU candidate countries with different enabling environments and social protections for older people, but with a similar level of connectedness within extended families. Semi-structured in-depth interviews with materially deprived divorced and widowed women, aged 65 years and older were conducted. The data was analysed based on the framework method. The analysis identifies the economic exclusion experienced by these women, along with the resilience and the different coping mechanisms that they demonstrate. Furthermore, it makes a cross-country comparison between Turkey and Serbia laying out similarities and differences between the two nations on this topic.
Analytical Instruments for Studying TSEI
Authors: Huntjens Patrick 
Published: March 2021

AbstractThe findings from literature in the previous chapters have been brought together in a conceptual framework (see Sect.3.9) and an analytical framework for Transformative Social-Ecological Innovation (Sect. 5.1). It’s main purpose is to study the dynamic interplay between actors and institutional structures influencing and inducing institutional change. This chapter furthermore provides a further operationalization of the TSEI analytical framework for analysing shifts in power dynamics (Sect. 5.2), by investigating a series or cluster of closely related action situations and mapping how power dynamics change. An example of TSEI-framework application is provided in Sect. 6.6. Finally, Sect. 5.3 provides a framework for analysing different levels of collective learning, which is considered as one of the key variables for studying the outputs of TSEI. Finally, this chapter highlights some important insights on collaborative action research and related methods (Sect. 5.4).
Introduction
Authors: Lemke Claudia 
Published: March 2021

AbstractThe Atlantic hurricane season terminated for this term with category-5 hurricanes such as Dorian (National Weather Service, 2019). Because of climate change, intense and damaging hurricanes are three times more frequent nowadays than 100 years ago (Grinsted, Ditlevsen & Hesselbjerg, 2019; McGrath, 2019). Likewise, scientific evidence suggests that climate change made Europe's major heatwave in 2018 more than twice as likely to occur (Schiermeier, 2018; World Weather Attribution, 2018).
Empirical findings
Authors: Lemke Claudia 
Published: March 2021

AbstractIn this chapter, the previously developed methodology of the MLSDI (see Chapter 4) is computed for a sample region, and the empirical findings are presented and discussed. Thereby, the knowledge (see Section 2.3.3; e.g. Weitz et al., 2018) and the sustainability gap (see Section 2.3.4; e.g. Hall et al., 2017) are tackled.
Discussion and conclusion
Authors: Lemke Claudia 
Published: March 2021

AbstractThis chapter discusses and reflects on the accomplished theoretical (see Chapter 2 and Chapter 3), methodological (see Chapter 4), and the empirical research (see Chapter 5). The present work is part of Phase C of the transdisciplinary research agenda in sustainability science (see Section 2.3.4; e.g. Lang et al., 2012). It draws on previous studies and problem framings from research and practice (Phase A), makes use of prior disclosures from the scientific and the practitioner community (Phase B), and finally provides new results that are relevant for both research and practice (Phase C).