bluuebunny/crossref_metadata_2025 huggingface dataset:
An analytical expression for R50% dependent on PTV surface area and volume: a lung SBRT comparison
Authors: Desai Dharmin D. , Johnson E. L. , Cordrey Ivan L.
Published: September 2020

In stereotactic body radiation therapy (SBRT), R50% is a common metric for intermediate dose spill and is defined in RTOG 0915 as the ratio of 50% isodose cloud volume (IDC50%) to the planning target volume (PTV). By coupling sound physical principles with the basic definition of intermediate dose spill, we derive an exact analytical expression for R50% for the case of a spherical volume. This expression for R50% depends on three quantities: the surface area of PTV (SAPTV), the volume of PTV (VPTV), and the dose gradient Δr. Validity of our analytical expression for R50% was confirmed via direct comparison to peer‐reviewed, multi‐institutional, diverse clinical data. The comparison of our R50% values computed from our analytical expression to the clinical data yielded an average percent difference of 3.8 ± 4.5%.
Retrospective analysis of the impact of respiratory motion in treatment margins for frameless lung SBRT based on respiratory‐correlated CBCT data‐sets
Authors: Thengumpallil Sheeba , Racine Damien , Germond Jean‐François , Péguret Nicolas , Bourhis Jean , Bochud François , Moeckli Raphaël
Published: September 2020

Purpose

To investigate the impact of respiratory motion in the treatment margins for lung SBRT frameless treatments and to validate our treatment margins using 4D CBCT data analysis.

Methods

Two hundred and twenty nine fractions with early stage NSCLC were retrospectively analyzed. All patients were treated in frameless and free breathing conditions. The treatment margins were calculated according to van Herk equation in Mid‐Ventilation. For each fraction, three 4D CBCT scans, pre‐ and postcorrection, and posttreatment, were acquired to assess target baseline shift, target localization accuracy and intra‐fraction motion errors. A bootstrap analysis was performed to assess the minimum number of patients required to define treatment margins.

Results

The retrospectively calculated target‐baseline shift, target localization accuracy and intra‐fraction motion errors agreed with the literature. The best tailored margins to our cohort of patients were retrospectively computed and resulted in agreement with already published data. The bootstrap analysis showed that fifteen patients were enough to assess treatment margins.

Conclusions

The treatment margins applied to our patient’s cohort resulted in good agreement with the retrospectively calculated margins based on 4D CBCT data. Moreover, the bootstrap analysis revealed to be a promising method to verify the reliability of the applied treatment margins for safe lung SBRT delivery.
Targeting foam cell formation in inflammatory brain diseases by the histone modifier MS‐275
Authors: Zierfuss Bettina , Weinhofer Isabelle , Buda Agnieszka , Popitsch Niko , Hess Lena , Moos Verena , Hametner Simon , Kemp Stephan , Köhler Wolfgang , Forss‐Petter Sonja , Seiser Christian , Berger Johannes
Published: September 2020

Objective

To assess class I‐histone deacetylase (HDAC) inhibition on formation of lipid‐accumulating, disease‐promoting phagocytes upon myelin load in vitro, relevant for neuroinflammatory disorders like multiple sclerosis (MS) and cerebral X‐linked adrenoleukodystrophy (X‐ALD).

Methods

Immunohistochemistry on postmortem brain tissue of acute MS (n = 6) and cerebral ALD (n = 4) cases to analyze activation and foam cell state of phagocytes. RNA‐Seq of in vitro differentiated healthy macrophages (n = 8) after sustained myelin‐loading to assess the metabolic shift associated with foam cell formation. RNA‐Seq analysis of genes linked to lipid degradation and export in MS‐275‐treated human HAP1 cells and RT‐qPCR analysis of HAP1 cells knocked out for individual members of class I HDACs or the corresponding enzymatically inactive knock‐in mutants. Investigation of intracellular lipid/myelin content after MS‐275 treatment of myelin‐laden human foam cells. Analysis of disease characteristic very long‐chain fatty acid (VLCFA) metabolism and inflammatory state in MS‐275‐treated X‐ALD macrophages.

Results

Enlarged foam cells coincided with a pro‐inflammatory, lesion‐promoting phenotype in postmortem tissue of MS and cerebral ALD patients. Healthy in vitro myelin laden foam cells upregulated genes linked to LXRα/PPARγ pathways and mimicked a program associated with tissue repair. Treating these cells with MS‐275, amplified this gene transcription program and significantly reduced lipid and cholesterol accumulation and, thus, foam cell formation. In macrophages derived from X‐ALD patients, MS‐275 improved the disease‐associated alterations of VLCFA metabolism and reduced the pro‐inflammatory status of these cells.

Interpretation

These findings identify class I‐HDAC inhibition as a potential novel strategy to prevent disease promoting foam cell formation in CNS inflammation.
Cryopreservation and Laser Nanowarming of Zebrafish Embryos Followed by Hatching and Spawning
Authors: Khosla Kanav , Kangas Joseph , Liu Yilin , Zhan Li , Daly Jonathan , Hagedorn Mary , Bischof John
Published: September 2020

This study shows for the first time the ability to rewarm cryopreserved zebrafish embryos that grow into adult fish capable of breeding normally. The protocol employs a single injection of cryoprotective agents (CPAs) and gold nanorods (GNRs) into the yolk and immersion in a precooling bath to dehydrate the perivitelline space. Then embryos are encapsulated within CPA and GNR droplets, plunged into liquid nitrogen, cryogenically stabilized, and rewarmed by a laser pulse. Postlaser nanowarming, embryos (n = 282) exhibit intact structure by 1 h (40%), continued development after 3 h (22%), movement after 24 h (11%), hatching after 48 h (9%), and swimming after Day 5 (3%). Finally, from fish that survives till Day 5, two larvae are grown to adulthood and spawned, yielding survival comparable to an unfrozen control. Future efforts will focus on improving the survival to adulthood and developing methods to cryopreserve large numbers of embryos for research, aquaculture, and biodiversity preservation.
One‐Pot Mannich, Aza‐Wittig and Dehydrofluorinative Aromatization Reactions for Direct Synthesis of 2,3‐Disubstituted 4‐Aminoquinolines
Authors: Zhang Xiaofeng , Ma Xiaoming , Qiu Weiqi , Awad JohnMark , Evans Jason , Zhang Wei
Published: September 2020

One‐pot synthesis of 2,3‐disubstituted 4‐aminoquinolines is developed through a three‐component reaction of 2‐azidobenzaldehydes, α‐fluoro‐β‐ketoesters and amines involving cascade Mannich, aza‐Wittig and dehydrofluorinative aromatization. The method is applicable to other functionalized quinolines. It is a pot, atom and step economy (PASE) synthesis of biologically interesting 4‐aminoquinolines relevant to hydroxychloroquine and chloroquine.

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HDL Nanoparticles Have Wound Healing and Anti‐Inflammatory Properties and Can Topically Deliver miRNAs
Authors: Wang Junyi , Calvert Andrea E. , Kaplan Nihal , McMahon Kaylin M. , Yang Wending , Lu Kurt Q. , Peng Han , Thaxton Colby Shad , Lavker Robert M.
Published: September 2020

microRNAs regulate numerous biological processes, making them potential therapeutic agents. Problems with delivery and stability of these molecules have limited their usefulness as treatments. It is demonstrated that synthetic high‐density lipoprotein nanoparticles (HDL NPs) topically applied to the intact ocular surface are taken up by epithelial and stromal cells. microRNAs complexed to HDL NPs (miR‐HDL NPs) are similarly taken up by cells and tissues and retain biological activity. Topical treatment of diabetic mice with either HDL NPs or miR‐HDL NPs significantly improves corneal reepithelialization following wounding compared with controls. Mouse corneas with alkali burn‐induced inflammation, topically treated with HDL NPs, display clinical, morphological, and immunological improvement. These results yield a novel HDL NP‐based eye drop for patients with compromised wound healing ability (diabetics) and/or corneal inflammatory diseases (e.g., dry eye).
Social cohesion revisited: Policy and practice in migrant concentration areas of Sydney and Melbourne
Authors: Sharples Rachel , Colic‐Peisker Val
Published: September 2020

This paper examines the understanding of social cohesion by policymakers, practitioners and residents, with particular reference to migrant concentration areas in Sydney and Melbourne. Ten suburbs we focus on had a high proportion of Muslim Australian residents and were socioeconomically disadvantaged at the time of the 2016 Australian Census. The paper is based on 52 in‐depth, semi‐structured interviews, mainly with professionals delivering local programmes and services, but also with residents. Based on interview data, the paper seeks to unpack the concept of social cohesion, particularly as it is applied to local programmes and discuss the understandings of the relationship of social cohesion with ethnic diversity and socioeconomic disadvantage. We found that most respondents considered “social cohesion” a positive feature of local and broader society, but the concept was variously understood. The understanding of its relationship with ethnic diversity and socioeconomic status of a local area also varied, but the predominant view was that social cohesion is put under stress by socioeconomic disadvantage. In some cases, “social cohesion” was understood, and criticised, as a coded policy formula for “preventing violent extremism” policies, especially in Muslim concentration areas, therefore with a potential to alienate local communities instead of helping them.
Evaluating multi‐step oxidative stabilization behavior of coal tar pitch‐based fiber
Authors: Niu Hao , Zuo Pingping , Shen Wenzhong , Qu Shijie
Published: September 2020

Oxidative stabilization is an important step for isotropic pitch‐based carbon fiber preparation; coal tar pitch‐based fiber is treated by multi‐step oxidative stabilization under various conditions to investigate the oxidative stabilization mechanism. The chemical structure changes of isotropic pitch‐based fiber during the oxidative stabilization and carbonization stage are systematically characterized by In‐situ diffuse reflectance infrared Fourier transform, elemental analysis, mass spectroscopy, X‐ray photoelectron spectroscopy, nuclear magnetic resonance, scanning electron microscope with an energy dispersive X‐ray spectrometer. These results show that the oxygen distribution gradient in oxidative stabilized fiber radial direction become homogeneously with the increasing of oxidation temperature and time under multi‐step oxidative stabilization. The resultant carbon fiber shows tensile strength of 942 ± 42 MPa and Young's modulus of 42.8 ± 3.1 GPa due to appropriate oxygen content, homogeneous oxygen distribution, more cross‐link bond (C‐O‐C) content, higher aromaticity and lower weight loss introduced in multi‐step oxidative stabilized pitch fiber. The multi‐step oxidative stabilization provides synergy effect between reaction rate and the oxygen diffusion rate as well as eliminates the oxygen concentration gradient, it provides an time‐saving and energy‐effective method for the oxidative stabilization of isotropic pitch‐based carbon material (pitch fiber, pitch microsphere, etc.) and improve the resultant carbon material performance.
Understanding and predicting future research impact at different career stages—A social network perspective
Authors: Zuo Zhiya , Zhao Kang
Published: September 2020

Performance assessment is ubiquitous and crucial in people analytics. Scientific impact, particularly, plays a significant role in the academia. This paper attempts to understand researchers' career trajectories by considering the research community as a social network, where individuals build ties with each other via coauthorship. The resulting linkage facilitates information flow and affects researchers' future impact. Consequently, we systematically investigate the career trajectories of researchers with respect to research impact using the social capital theory as our theoretical foundation. Specifically, for early‐stage and mid‐career academics, we find that connections with prominent researchers associate with greater impact. Brokerage positions, in addition, are beneficial to a researcher's research impact in the long run. For senior researchers, however, the only social network feature that significantly affects their future impact is the reputation of their recently built ties. Finally, we build predictive models on future research impact which can be leveraged by both organizations and individuals. This paper provides empirical evidence for how social networks provide signals on researchers' career dynamics guided by social capital theory. Our findings have implications for individual researchers to strategically plan and promote their careers and for research institutions to better evaluate current as well as prospective employees.
Reactive Oxygen Species: Potential Regulatory Molecules in Response to Hypomagnetic Field Exposure
Authors: Zhang Bingfang , Tian Lanxiang
Published: September 2020

Organisms, including humans, could be exposed to hypomagnetic fields (HMFs, intensity <5 μT), e.g. in some artificially shielded magnetic environments and during deep‐space flights. Previous studies have demonstrated that HMF exposure could have negative effects on the central nervous system and embryonic development in many animals. However, the underlying mechanisms remain unknown. Studies have revealed that HMFs affect cellular reactive oxygen species (ROS) levels and thereby alter physiological and biological processes in organisms. ROS, the major component of highly active free radicals, which are ubiquitous in biological systems, were hypothesized to be the candidate signaling molecules that regulate diverse physiological processes in response to changes in magnetic fields. Here, we summarize the recent advances in the study of HMF‐induced negative effects on the central nervous system and early embryonic development in animals, focusing on cellular ROS and their role in response to HMFs. Furthermore, we discuss the potential mechanism through which HMFs regulate ROS levels in cells. © 2020 Bioelectromagnetics Society
Effects of childhood trauma experience and COMT Val158Met polymorphism on brain connectivity in a multimodal MRI study
Authors: Tian Tian , Li Jia , Zhang Guiling , Wang Jian , Liu Dong , Wan Changhua , Fang Jicheng , Wu Di , Zhou Yiran , Zhu Wenzhen
Published: September 2020

Childhood adversity may act as a stressor to produce a cascade of neurobiological effects that irreversibly alter neural development, setting the stage for developing psychopathology in adulthood. The catechol‐O‐methyltransferase (COMT) Val158Met polymorphism has received much attention as a candidate gene associated with environmental adversity, modifying risk for psychopathology. In this study, we aim to see how gene × brain × environment models give a more integrative understanding of brain modifications that contribute to predicting psychopathology related to childhood adversity. A large nonclinical sample of young adults completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal magnetic resonance imaging (MRI) scans, and genotyping. We utilized graph‐based connectivity analysis in morphometric similarity mapping and resting‐state functional MRI to investigate brain alterations. Relationships among COMT genotypes, CTQ score, imaging phenotypes, and behavioral scores were identified by multiple regression and mediation effect analysis. Significant main effect of CTQ score was found in anatomic connectivity of orbitofrontal cortex that was an outstanding mediator supporting the relationship between CTQ score and anxiety/harm‐avoiding personality. We also noted the main effect of childhood trauma on reorganization of functional connectivity within the language network. Additionally, we found genotype × CTQ score interactions on functional connectivity of the right frontoparietal network as well as anatomic connectivity of motor and limbic regions. Our data demonstrate childhood adversity and COMT genotypes are associated with abnormal brain connectivity, structurally and functionally. Early identification of individuals at risk, assessment of brain abnormality, and cognitive interventions may help to prevent or limit negative outcomes.
A deep learning nomogram kit for predicting metastatic lymph nodes in rectal cancer
Authors: Ding Lei , Liu Guangwei , Zhang Xianxiang , Liu Shanglong , Li Shuai , Zhang Zhengdong , Guo Yuting , Lu Yun
Published: September 2020

Background

Preoperative diagnoses of metastatic lymph nodes (LNs) by the most advanced deep learning technology of Faster Region‐based Convolutional Neural Network (Faster R‐CNN) have not yet been reported.

Materials and Methods

In total, 545 patients with pathologically confirmed rectal cancer between January 2016 and March 2019 were included and were randomly allocated with a split ratio of 2:1 to the training and validation sets, respectively. The MRI images for metastatic LNs were evaluated by Faster R‐CNN. Multivariate regression analyses were used to develop the predictive models. Faster R‐CNN nomograms were constructed based on the multivariate analyses in the training sets and were validated in the validation sets.

Results

The Faster R‐CNN nomogram for predicting metastatic LN status contained predictors of age, metastatic LNs by Faster R‐CNN and differentiation degrees of tumors, with areas under the curves (AUCs) of 0.862 (95% CI: 0.816‐0.909) and 0.920 (95% CI: 0.876‐0.964) in the training and validation sets, respectively. The Faster R‐CNN nomogram for predicting LN metastasis degree contained predictors of metastatic LNs by Faster R‐CNN and differentiation degrees of tumors, with AUCs of 0.859 (95% CI: 0.804‐0.913) and 0.886 (95% CI: 0.822‐0.950) in the training and validation sets, respectively. Calibration plots and decision curve analyses demonstrated good calibrations and clinical utilities. The two nomograms were used jointly as a kit for predicting metastatic LNs.

Conclusion

The Faster R‐CNN nomogram kit exhibits excellent performance in discrimination, calibration, and clinical utility and is convenient and reliable for predicting metastatic LNs preoperatively.

Clinical trial registration: ChiCTR‐DDD‐17013842.
Recent Advances in Applying Carbonyl‐stabilized Phosphorus Ylides for Catalysis
Authors: Shi Yang , Pan Bo‐Wen , Yu Jin‐Sheng , Zhou Ying , Zhou Jian
Published: September 2020

The exploration of new catalytic properties of the known functionalities would facilitate the exploitation of new ligands and/or organocatalysts that are able to achieve reactivity and selectivity unattainable by known ones. In this context, carbonyl‐stabilized phosphorus ylides have emerged as a type of novel ligand motifs and organocatalysts, exhibiting versatile catalytic activity towards some important organic reactions such as cross‐couplings, cyanation, CO2 fixation. This Minireview summarizes these recent advances, highlights the advantages and limitations, and outlines synthetic opportunities still open for further investigation.
Regioselective Gas‐Phase n‐Butane Transfer Dehydrogenation via Silica‐Supported Pincer‐Iridium Complexes
Authors: Sheludko Boris , Castro Cristina F. , Khalap Chaitanya A. , Emge Thomas J. , Goldman Alan S. , Celik Fuat E.
Published: September 2020

The production of olefins via on‐purpose dehydrogenation of alkanes allows for a more efficient, selective and lower cost alternative to processes such as steam cracking. Silica‐supported pincer‐iridium complexes of the form [(≡SiO−R4POCOP)Ir(CO)] (R4POCOP=κ3‐C6H3‐2,6‐(OPR2)2) are effective for acceptorless alkane dehydrogenation, and have been shown stable up to 300 °C. However, while solution‐phase analogues of such species have demonstrated high regioselectivity for terminal olefin production under transfer dehydrogenation conditions at or below 240 °C, in open systems at 300 °C, regioselectivity under acceptorless dehydrogenation conditions is consistently low. In this work, complexes [(≡SiO−tBu4POCOP)Ir(CO)] (1) and [(≡SiO−iPr4PCP)Ir(CO)] (2) were synthesized via immobilization of molecular precursors. These complexes were used for gas‐phase butane transfer dehydrogenation using increasingly sterically demanding olefins, resulting in observed selectivities of up to 77 %. The results indicate that the active site is conserved upon immobilization.
A Local D4h Symmetric Dysprosium(III) Single‐Molecule Magnet with an Energy Barrier Exceeding 2000 K**
Authors: Ding Xia‐Li , Zhai Yuan‐Qi , Han Tian , Chen Wei‐Peng , Ding You‐Song , Zheng Yan‐Zhen
Published: September 2020

Three six‐coordinate DyIII single‐molecule magnets (SMMs) [Dy(OtBu)2(L)4]+ with local D4h symmetry are obtained by optimizing the equatorial ligands. One of the compounds with L=4‐phenylpyridine shows an energy barrier (Ueff) of 2075(11) K, which is the third largest Ueff, and the first Ueff>2000 K for SMMs with axial‐type symmetry so far. Ab initio analysis indicates that the exceptional uniaxial magnetic anisotropy is deeply related to the axially compressed octahedral geometry. This work provides a new insight into the local D4h symmetry for high‐performance SMMs.
Halogen‐Bonded BODIPY Frameworks with Tunable Optical Features**
Authors: Özcan Emrah , Dedeoglu Burcu , Chumakov Yuri , Gürek Ayşe Gül , Zorlu Yunus , Çoşut Bünyemin , Menaf Ayhan Mehmet
Published: September 2020

The ability to tune the optical features of BODIPY materials in the solid state is essential for their photorelated application and requires efficient control of the crystal packing. In this study, such control of BODIPY supramolecular assemblies was achieved by deliberate design and synthesis of a BODIPY containing a strong halogen‐bond (XB) acceptor (−NO2) and donor (I, Br) to mediate XB interactions. The di‐halogenated structures formed isostructural mono‐coordinate motif B3, B4 (1D tubular structure) and symmetric bifurcated motif B4‐II (1D zigzag chains structure) through N−O⋅⋅⋅I, Br XB interactions. These XB interactions promote singlet‐to‐triplet intersystem crossing and triplet‐to‐singlet reverse intersystem crossing due to partial delocalization of oxygen electrons onto Br and I, which leads to unexpected fluorescence enhancement of B4‐II. Finally, the indirect optical band gaps of B3, B4 and B4‐II were amenable to tuning in the range of 1.85–2.50  eV by XB‐driven crystal packings.
Anion Receptors for the Discrimination of ATP and ADP in Biological Media
Authors: Butler Stephen J. , Jolliffe Katrina A.
Published: September 2020

The design and synthesis of molecular receptors for the selective binding of nucleoside phosphate anions (e. g. ATP, ADP, GTP, GDP, UDP) in aqueous media at physiological pH is a valuable research endeavour, which could lead to new sensing tools for biomedical and drug discovery research. However, this target is very challenging due to similarities in anion size, structure and charge. This Minireview provides an account of the development of receptors capable of discriminating between ATP and ADP, and their utilisation in biological sensing applications. Particular focus is given to the application of receptors for the determination of ATP or ADP concentrations in biological media, tracking ATP levels (or the ATP/ADP ratio) in cells using fluorescence microscopy, or real‐time monitoring of enzyme reactions involving ATP and ADP in vitro.
Tandem Homometallic or Multimetallic Catalysis for Assembly of Base‐Modified Nucleosides
Authors: Shet Harshita , Bhilare Shatrughn , Sanghvi Yogesh S. , Kapdi Anant R.
Published: September 2020

Tandem catalysis has been at the forefront of synthesis in the past decade due to the reduction in the number of steps and purification needed for the synthesis of commercially relevant molecules. With the right combination of catalyst systems, which could be homometallic or multimetallic, one can construct complex structural motifs in a one‐pot procedure without the requirement for the isolation of the intermediates, reducing both reagent waste and time. Over the years, application of tandem catalysis has certainly extended towards arene and heteroarene motifs; nucleoside modification using such a strategy has been rare. In this regard, we would like to report herein the development of numerous homometallic and multimetallic tandem catalytic protocols for the modification of nucleosides, providing efficient access to a diverse range of molecules with promising fluorescent properties, as well as pharmaceutically relevant antiviral drugs such as FV‐100. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Double tandem one‐pot Sonogashira/cyclization of 5‐IdU for the synthesis of FV‐100 and analogs

Basic Protocol 2: Double tandem one‐pot Heck/Suzuki–Miyaura of 5‐IdU for the synthesis of fluorescent nucleoside analogs

Basic Protocol 3: Double tandem one‐pot Suzuki–Miyaura cross‐coupling of 5‐IdU for the synthesis of fluorescent nucleoside analogs

Basic Protocol 4: Double tandem one‐pot amination/amidation for the synthesis of Sangivamycin precursor

Basic Protocol 5: Triple tandem one‐pot chemoselective etherification/Sonogashira coupling/cyclization for synthesis of BCNA analogs

Basic Protocol 6: Triple tandem one‐pot sequential Heck/borylation/Suzuki‐Miyaura reaction
Histone Purification Combined with High‐Resolution Mass Spectrometry to Examine Histone Post‐Translational Modifications and Histone Variants in Caenorhabditis elegans
Authors: Millan‐Ariño Lluís , Yuan Zuo‐Fei , Oomen Marlies E. , Brandenburg Simone , Chernobrovkin Alexey , Salignon Jérôme , Körner Lioba , Zubarev Roman A. , Garcia Benjamin A. , Riedel Christian G.
Published: September 2020

Histones are the major proteinaceous component of chromatin in eukaryotic cells and an important part of the epigenome, affecting most DNA‐related events, including transcription, DNA replication, and chromosome segregation. The properties of histones are greatly influenced by their post‐translational modifications (PTMs), over 200 of which are known today. Given this large number, researchers need sophisticated methods to study histone PTMs comprehensively. In particular, mass spectrometry (MS)−based approaches have gained popularity, allowing for the quantification of dozens of histone PTMs at once. Using these approaches, even the study of co‐occurring PTMs and the discovery of novel PTMs become feasible. The success of MS‐based approaches relies substantially on obtaining pure and well‐preserved histones for analysis, which can be difficult depending on the source material. Caenorhabditis elegans has been a popular model organism to study the epigenome, but isolation of pure histones from these animals has been challenging. Here, we address this issue, presenting a method for efficient isolation of pure histone proteins from C. elegans at good yield. Further, we describe an MS pipeline optimized for accurate relative quantification of histone PTMs from C. elegans. We alkylate and tryptically digest the histones, analyze them by bottom‐up MS, and then evaluate the resulting data by a C. elegans−adapted version of the software EpiProfile 2.0. Finally, we show the utility of this pipeline by determining differences in histone PTMs between C. elegans strains that age at different rates and thereby achieve very different lifespans. © 2020 The Authors.

Basic Protocol 1: Large‐scale growth and harvesting of synchronized C. elegans

Basic Protocol 2: Nuclear preparation, histone extraction, and histone purification

Basic Protocol 3: Bottom‐up mass spectrometry analysis of histone PTMs and histone variants
Development of near‐infrared reflectance spectroscopy calibration for sugar content in ground soybean seed using Perten DA7250 analyzer
Authors: Lord Nick , Shang Chao , Rosso Luciana , Zhang Bo
Published: September 2020

There is growing interest in developing calibrations for soybean [Glycine max (L.) Merr.] seed sugars on near‐infrared reflectance spectroscopy (NIRS) instruments to increase the efficiency of sugar profiling. In this study, a set of 253 samples from Virginia Tech's soybean germplasm with a wide range of sugar content were used to create prediction models for sucrose, raffinose, and stachyose in ground soybean seed on the Perten DA7250 NIRS instrument. Following acquisition of spectral data, seed sugars were extracted from ground samples and analyzed using high‐performance liquid chromatography (HPLC) to obtain reference data. Spectral and HPLC data were modeled using partial least squares regression (PLSR) on CAMO Unscrambler X software and internally cross‐validated using the same software. Resulting calibrations showed high quantitative accuracy with the coefficient of determination of calibration (R2C) = .901, the coefficient of determination of cross‐validation (R2CV) = .869, root mean squared error of calibration (RMSEC) = .516, and root mean squared error of cross‐validation (RMSECV) of .596 for sucrose and R2C = .911, R2CV = .891, RMSEC = .361, and RMSECV of .405 for stachyose. These calibrations appear suitable for use in breeding operations. Meanwhile, performance of the raffinose calibration remained poor with R2C = .568, R2CV = .476, RMSEC = .129, and RMSECV = .143. Alternative methods for more accurate and rapid quantification of raffinose concentration in soybean seed should be investigated.
Antiparasitic activities of novel pyrimidine N‐acylhydrazone hybrids
Authors: Poletto Julia , da Silva Michael J. V. , Jacomini Andrey P. , Bidóia Danielle L. , Volpato Hélito , Nakamura Celso Vataru , Rosa Fernanda A.
Published: September 2020

In this article, a series of 29 new pyrimidine N‐acylhydrazone hybrids were synthesized and evaluated in vitro against Leishmania amazonensis and Trypanosoma cruzi protozoa that cause the neglected diseases cutaneous leishmaniasis and Chagas disease, respectively. Eight of the target compounds showed significant antiprotozoal activities with IC50 values in 4.3–33.6 μM range. The more active compound 4f exhibited selectivity index greater than 15 and drug‐like properties based on Lipinski's rule.
Monitoring soil erosion on agricultural land: results and implications for the Rother valley, West Sussex, UK
Authors: Boardman John , Burt Tim , Foster Ian
Published: September 2020

Monitoring has played a key role in understanding the rates, extent and frequency of erosion on agricultural land and this includes projects in Switzerland, Germany and the UK. In this case we focus on highly erodible soils in the Rother valley, West Sussex, southern England on which grow a range of arable crops throughout the year. Erosion rates and extent are high, particularly in response to exceptionally wet periods in the early winter. In the monitored period, rates on summer crops were relatively low due to an absence of intense summer storms. In the years 2015–2020, erosion was localized to where limited areas of bare ground coincided with heavy winter rainfall. Issues of river pollution, associated with excessive sedimentation, off‐site flooding and a high degree of connectivity between arable fields and the river, are of increasing concern. Mitigation measures need to be expanded to protect freshwater systems and properties. This study has implications for similar programmes in intensely farmed regions. © 2020 John Wiley & Sons, Ltd.
Application of Bioavailability Models to Derive Chronic Guideline Values for Nickel in Freshwaters of Australia and New Zealand
Authors: Stauber Jenny , Golding Lisa , Peters Adam , Merrington Graham , Adams Merrin , Binet Monique , Batley Graeme , Gissi Francesca , McKnight Kitty , Garman Emily , Middleton Ellie , Gadd Jennifer , Schlekat Chris
Published: September 2020

There has been an increased emphasis on incorporating bioavailability-based approaches into freshwater guideline value derivations for metals in the Australian and New Zealand water quality guidelines. Four bioavailability models were compared: the existing European biotic ligand model (European Union BLM) and a softwater BLM, together with 2 newly developed multiple linear regressions (MLRs)—a trophic level-specific MLR and a pooled MLR. Each of the 4 models was used to normalize a nickel ecotoxicity dataset (combined tropical and temperate data) to an index condition of pH 7.5, 6 mg Ca/L, 4 mg Mg/L, (i.e., approximately 30 mg CaCO3/L hardness), and 0.5 mg DOC/L. The trophic level-specific MLR outperformed the other 3 models, with 79% of the predicted 10% effect concentration (EC10) values within a factor of 2 of the observed EC10 values. All 4 models gave similar normalized species sensitivity distributions and similar estimates of protective concentrations (PCs). Based on the index condition water chemistry proposed as the basis of the national guideline value, a protective concentration for 95% of species (PC95) of 3 µg Ni/L was derived. This guideline value can be adjusted up and down to account for site-specific water chemistries. Predictions of PC95 values for 20 different typical water chemistries for Australia and New Zealand varied by >40-fold, which confirmed that correction for nickel bioavailability is critical for the derivation of site-specific guideline values. Environ Toxicol Chem 2021;40:100–112. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Derivation of bioavailability-based guidelines for nickel in freshwaters after normalization of ecotoxicity data using trophic level-specific multiple linear regression (MLRs). SSD = species sensitivity distribution.
Influence of sample size and analytic approach on stability and interpretation of brain‐behavior correlations in task‐related fMRI data
Authors: Grady Cheryl L. , Rieck Jenny R. , Nichol Daniel , Rodrigue Karen M. , Kennedy Kristen M.
Published: September 2020

Limited statistical power due to small sample sizes is a problem in fMRI research. Most of the work to date has examined the impact of sample size on task‐related activation, with less attention paid to the influence of sample size on brain‐behavior correlations, especially in actual experimental fMRI data. We addressed this issue using two large data sets (a working memory task, N = 171, and a relational processing task, N = 865) and both univariate and multivariate approaches to voxel‐wise correlations. We created subsamples of different sizes and calculated correlations between task‐related activity at each voxel and task performance. Across both data sets the magnitude of the brain‐behavior correlations decreased and similarity across spatial maps increased with larger sample sizes. The multivariate technique identified more extensive correlated areas and more similarity across spatial maps, suggesting that a multivariate approach would provide a consistent advantage over univariate approaches in the stability of brain‐behavior correlations. In addition, the multivariate analyses showed that a sample size of roughly 80 or more participants would be needed for stable estimates of correlation magnitude in these data sets. Importantly, a number of additional factors would likely influence the choice of sample size for assessing such correlations in any given experiment, including the cognitive task of interest and the amount of data collected per participant. Our results provide novel experimental evidence in two independent data sets that the sample size commonly used in fMRI studies of 20–30 participants is very unlikely to be sufficient for obtaining reproducible brain‐behavior correlations, regardless of analytic approach.
Deglobalization and talent sourcing: Cross‐national evidence from high‐tech firms
Authors: Farndale Elaine , Thite Mohan , Budhwar Pawan , Kwon Bora
Published: September 2020

As corporate globalization is restricted through changes in macro‐environments, firms traditionally reliant on global talent pools are suffering. This is particularly true for high‐tech firms' seeking to source high‐skilled STEM (science, technology, engineering, and mathematics) talent. The aim of this study, in line with the special issue, is to explore the impact of macro‐level trends in national government policy and political climates on high‐tech firms seeking to source high‐skilled STEM talent. By applying coevolutionary reasoning, we develop propositions that link the macro environment with corporate strategizing. A multi‐respondent, qualitative research design is adopted, involving interviews and focus groups with 40 practitioners and industry experts. Through qualitative data analysis, we identify emergent adaptations to corporate talent sourcing activities for dealing with increasing STEM shortages linked to deglobalization. As the data highlight, the adaptations are a consequence of both internal strategic factors as well as external institutional forces and the interplay between the two. Implications for future research and practice are discussed.
Frequency and molecular characteristics of PALB2‐associated cancers in Russian patients
Authors: Preobrazhenskaya Elena V. , Shleykina Alla U. , Gorustovich Olga A. , Martianov Alexandr S. , Bizin Ilya V. , Anisimova Elena I. , Sokolova Tatjana N. , Chuinyshena Svetlana A. , Kuligina Ekatherina Sh. , Togo Alexandr V. , Belyaev Alexey M. , Ivantsov Alexandr O. , Sokolenko Anna P. , Imyanitov Evgeny N.
Published: September 2020

PALB2 is а high‐penetrance gene for hereditary breast cancer (BC). Our study aimed to investigate the spectrum of PALB2 mutations in Russian cancer patients. PALB2 sequencing revealed pathogenic variants in 3/190 (1.6%) young‐onset and/or familial and/or bilateral BC cases but none in 96 ovarian cancer (OC) or 172 pancreatic cancer patients. Subsequently, seven recurrent PALB2 pathogenic alleles were selected from this and previous Slavic studies and tested in an extended patient series. PALB2 pathogenic variants were detected in 5/585 (0.9%) “high‐risk” BC, 10/1508 (0.7%) consecutive BC and 5/1802 (0.3%) OC cases. Haplotyping suggested that subjects with Slavic alleles c.509‐510delGA (n = 10) and c.172‐175delTTGT (n = 4) as well as carriers of Finnish c.1592delT mutation (n = 4) originated from a single founder each, while PALB2 p.R414X allele (n = 4) had at least two independent founders. Somatic loss of heterozygosity (LOH) was revealed in 5/10 chemonaive BCs and in 0/2 BC samples obtained after neoadjuvant therapy. Multigene sequencing identified somatic PALB2 inactivating point mutation in one out of two tumors without PALB2 LOH but in none of four BCs with PALB2 LOH. Genomic instability, as determined by NGS, was observed in four out of five tumors with biallelic PALB2 inactivation but not in the BC sample with the preserved wild‐type PALB2 allele. PALB2 germ‐line mutations contribute to a small fraction of cancer cases in Russia. The majority although not all PALB2‐driven BCs have somatic inactivation of the remaining PALB2 allele and therefore potential sensitivity to platinum compounds and PARP inhibitors.
A potential role for aspirin in the prevention and treatment of cholangiocarcinoma
Authors: Shen Xizi , Shen Xingping
Published: September 2020

Cholangiocarcinoma is the second most common primary hepatic cancer, with a rising incidence worldwide. Owing to late diagnosis and limited treatment options, the prognosis for cholangiocarcinoma remains dismal, compelling a search for new treatments. As aspirin exhibits a well‐supported chemopreventive effect on common cancers, researchers have proposed using aspirin as a potential preventive and adjuvant agent for cholangiocarcinoma. In the present review of the literature, we provide a background on cholangiocarcinoma and potential mechanisms of action underlying the anticancer effect of aspirin. Although the exact mode of action remains unclear, multiple downstream effects of aspirin may interfere with cholangiocarcinogenesis, tumour growth and metastasis—including inhibiting the COX‐2 pathway, preventing platelet aggregation and modulating certain proteins and signalling. This review also summarises evidence to support the chemopreventive effects of aspirin on common cancers, particularly colorectal cancer and discusses studies that report a positive outcome of aspirin in cholangiocarcinoma. Regular use of aspirin is associated with a reduced incidence of colorectal cancers as well as cholangiocarcinomas, and improved survival. Aspirin thus appears to play a role in the primary prevention and treatment of cholangiocarcinoma. However, further studies are needed to confirm these benefits and to establish a cause‐and‐effect relationship.
A generic Systems Engineering process tailoring methodology, based on lessons from MeerKAT
Authors: Küsel Thomas W.
Published: September 2020

Each system is unique and requires tailoring of the systems engineering process to ensure that it is applied effectively and efficiently. The concept of tailoring is well recognized, but there is limited literature on generic tailoring methodologies. In this paper, a simple yet effective generic tailoring methodology is proposed. The paper identifies the system characteristics that should be considered during the tailoring process and key performance indicators. The MeerKAT project is used as a case study to derive the methodology and is used to illustrate its application.
Towards a Common Systems Engineering Methodology to Cover a Complete System Development Process
Authors: Morkevicius Aurelijus , Aleksandraviciene Aiste , Armonas Andrius , Fanmuy Gauthier
Published: September 2020

Model‐Based System Engineering (MBSE) provides the ability to experience systems early from conceptual phases, and is one of the masterpieces of the Industry Renaissance. We see now in many Industries that we are leaving the world of experimentation to an effective and growing deployment of MBSE. One of the common challenges in industry is to bridge the gap between systems engineering studies and product development in a digital continuity and providing a seamless system experience. This paper presents an end‐to‐end systems engineering methodology, MagicGrid, extending the MBSE Grid methodology, to consider all the viewpoints of engineering of a cyber‐physical system.
Reverse architecting conventional footwear. Towards an A3 Architecture Overview that supports development of alternative footwear architectures.
Authors: Dankers Winnie , Bonnema Gerrit Maarten
Published: September 2020

The architecture of contemporary footwear is the result of a long history of footwear development. In this history, part of the argumentation behind the architecture has been lost, causing footwear developers to make decisions based on habits and badly underpinned assumptions. New insights on the negative influence of most conventional footwear on human (foot) health and the design freedom that arises from modern manufacturing techniques, create the urge to reconsider the common way of developing. By reverse architecting conventional footwear, this paper derives an A3 Architecture Overview of conventional footwear. In the future this overview should provide a tool for enabling product evolution towards healthy footwear, by allowing developers to consciously and purposefully deviate from ‘the standard architecture’ while taking into account the consequences of design decisions they make. The approach that is described in this paper is also applicable to the development of architecture overviews for other product families.
Managing Integration and Verification Risks of the SKA Radio Telescope
Authors: Lord Richard T. , Gammon Donald
Published: September 2020

The Square Kilometre Array (SKA) project is an international effort to build the world's largest radio telescope (SKAO 2020). A brief overview of the SKA project is provided, outlining some of the major challenges that such a project needs to manage. These challenges give rise to risk, which could lead to schedule delays, cost overruns and degraded performance of the final system. This paper describes how the integration and verification (I&V) of this radio telescope has been planned, and how the objective of mitigating risk has been an underlying motivation throughout this planning effort.
Risk and Opportunity Management for Project Selection in the Road Construction Industry
Authors: Stisen Martha , Syverud Elisabet
Published: September 2020

Road Construction projects failing to meet deadlines or budget costs puts burden on the construction company. The consequence may be economically unprofitable projects that significantly weaken the company's financial performance. To avoid unnecessary use of resources, the companies must identify and filter out unprofitable projects as early as possible. This paper lays out a process for use with road construction companies to improve their ability to choose profitable projects. The focus is on active management of risk and opportunity in the pre‐selection phase.

The research is based on a case study at a road construction company. We interviewed key personnel to understand their main needs. We validated the proposed solution through a survey of nine employees at the same company.

Our research resulted in a new method targeted to guide construction companies through the project selection process. The developed process flow illustrates the sequence and interaction of the different process stages. The risk and opportunity process is complemented with a check list, a risk and opportunity register, and the associated risk and opportunity matrix.
Creating and Applying Total Cost Model: A Case Study at Maritime Company for Last Time Buy Estimation
Authors: Sletaker Lasse Andre , Gonsholt Arild , Muller Gerrit , Kokkula Satyanarayana
Published: September 2020

Kongsberg Maritime (KM) experiences growth in the number of reactive obsolescence events. Time constraints in the decision‐making process limit options on how to resolve obsolescence. The total cost trajectory of labor and money consumed to resolve obsolescence is not sustainable for KM going forward.

Last time buy (LTB) is one of many tools in obsolescence management. LTB is attractive because it does not require reengineering, requalification, or redesign. Despite its benefits, LTB should only be used if the total cost of LTB outweighs other alternatives.

In this study a model was created to predict component obsolescence and quantifying the total cost of LTB. The research assumes obsolescence management less effective when dominated by LTBs. By proactively using this model, decision‐makers can evaluate alternatives compared to LTB selecting the most cost‐effective solution. Feedback from decision‐makers confirms a need to have, and willingness to use, the model.
Addressing Cognitive Bias in Systems Engineering Teams
Authors: McDermott Thomas A. , Folds Dennis J. , Hallo Leonie
Published: September 2020

Cognitive bias is a general issue in human decision making. It is easy to assume there is less bias in engineering, systems engineering, and program management, as these are generally considered rational processes. However, human decision making is almost always affected by bias. In the systems engineering practice as well as training systems engineers, we find directly addressing principles of human cognition, decision‐making, and bias to be an important part of individual and team learning. In the context of systems engineering competencies, these principles are core to mastery of systems and critical thinking, facilitation, and team dynamics. This paper discusses the characteristics of thinking, cognition, and decision‐making; conceptual approaches in psychology that frame these characteristics in the context of human decisions; common biases that affect decisions in the domain of systems engineering; and application of systems thinking tools to help overcome these issues.