bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical Characterization and Phytotoxic Effects of the Aerial Parts of Ruzigrass (Urochloa ruziziensis)
Authors: Pereira Moreno Beatriz , Mantovanelli Gislaine Cristiane , Lopes Ricardo Letycia , Silva Adriano Antônio , Silvério De Oliveira Rubem , Ishii‐Iwamoto Emy Luiza , Sarragiotto Maria Helena , Baldoqui Debora Cristina
Published: February 2020

Studies of the phytotoxic effects between plants can be a crucial tool in the discovery of innovative compounds with herbicide potential. In this sense, we can highlight ruzigrass (Urochloa ruziziensis), which is traditionally used in the crop rotation system in order to reduce weed emergence. The aim of this work was to characterize the secondary metabolites of ruzigrass and to evaluate its phytotoxic effects. In total, eight compounds were isolated: friedelin, oleanolic acid, α‐amyrin, 1‐dehydrodiosgenone, sitosterol and stigmasterol glycosides, tricin and p‐coumaric acid. Phytotoxic effects of the crude methanolic extract and fractions of ruzigrass were assessed using germination rate, initial seedling growth, and biomass of Bidens pilosa, Euphorbia heterophylla and Ipomoea grandifolia. Chemometric analysis discriminated the weed species into three groups, and B. pilosa was the most affected by fractions of ruzigrass. The phytotoxic activities of 1‐dehydrodiosgenone, tricin, and p‐coumaric acid are also reported, and p‐coumaric acid and 1‐dehydrodiosgenone were active against B. pilosa.
Identification of a Unique Azaphilone Produced by Chaetomium globosum Isolated from Polygonatum sibiricum
Authors: Song Chenggang , Ding Gang , Wu Gang , Yang Jian , Zhang Mingzhe , Wang Haoyu , Wei Dongsheng , Qin Jianchun , Guo Lanping
Published: February 2020

A new azaphilone, chaephilone E, eight azaphilone derivatives, and three chaetoglobosins were isolated from endophytic fungi Chaetomium globosum. The structures of the compounds were elucidated by 1D and 2D NMR as well as HR‐ESI‐MS data, and the absolute configuration of chaephilone E was established on the basis of electronic circular dichroism and NOESY spectrum. The activity of chaephilone E was evaluated via the cytotoxic assay (human hepatoma cell lines HepG‐2) and brine shrimp (Artemia salina) bioassay.
Hijacking Translation Initiation for Synthetic Biology
Authors: Tharp Jeffery M. , Krahn Natalie , Varshney Umesh , Söll Dieter
Published: February 2020

Genetic code expansion (GCE) has revolutionized the field of protein chemistry. Over the past several decades more than 150 different noncanonical amino acids (ncAAs) have been co‐translationally installed into proteins within various host organisms. The vast majority of these ncAAs have been incorporated between the start and stop codons within an open reading frame. This requires that the ncAA be able to form a peptide bond at the α‐amine, limiting the types of molecules that can be genetically encoded. In contrast, the α‐amine of the initiating amino acid is not required for peptide bond formation. Therefore, including the initiator position in GCE allows for co‐translational insertion of more diverse molecules that are modified, or completely lacking an α‐amine. This review explores various methods which have been used to initiate protein synthesis with diverse molecules both in vitro and in vivo.
Predicting the risk of late futile outcome after transcatheter aortic valve implantation
Authors: Zusman Oren , Barbash M. Israel , Guetta Victor , Finkelstein Ariel , Assali Abid , Segev Amit , Orvin Katia , Barsheshet Alon , Younis Arwa , Witberg Guy , Kornowski Ran , Danenberg Haim , Landes Uri
Published: February 2020

Background

Transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) risk assessment is still developing and mostly concerned with mortality in the periprocedural period. We therefore sought to develop and then validate a score to predict 1‐year adverse outcome.

Methods

Patients that underwent TAVI for severe AS in the Israeli registry. Patients with unsuccessful/suboptimal implantation were excluded. The cohort was split to derivation/validation cohorts by a ratio of 70:30. The outcome was defined as 1‐year composite of mortality, stroke, and no improvement in NYHA class (vs. baseline). Logistic regression was used to fit the prediction model.

Results

Out of 2,440 patients meeting inclusion criteria, 276 were excluded, leaving 2,160 patients for both cohorts. At 1 year, 299 (14%) patients experienced the adverse (“futile”) outcome. The derived prediction model included mean aortic valve (AV) gradient, previous pacemaker, previous oncological disease, need for diuretics, baseline NYHA class, hemoglobin and creatinine levels, and nonfemoral access site. The model's area under the curve (AUC) was 0.69 in the derivation and 0.70 in the validation cohort. Performance of other scores in the validation cohort were lower (0.60 for STS, 0.55 for Euroscore2, 0.56 for TVT score, and 0.53 for TAVI2‐score, p = .03). Based on three risk tiers, patients had a low risk (20/306, 7% futility), a medium risk (50/304, 17%), and high risk (18/37, 49%) for futility.

Conclusions

The TAVI futility risk model can be used to provide further insight regarding prediction measures and/or patients' outcomes outside of the periprocedural period (NCT02023060).
Antenatal diagnosis of absence of septum pellucidum
Authors: Ben M'Barek Imane , Tassin Mikael , Guët Agnes , Simon Isabelle , Mairovitz Valerie , Mandelbrot Laurent , Picone Olivier
Published: February 2020

The absence of septum pellucidum (ASP) is a rare disease, which affects the structure of the brain. It is either isolated or associated with various congenital brain malformations. The diagnosis of ASP can be performed by second‐trimester ultrasound. When the ASP is isolated, prenatal counseling is optimistic regarding neurological outcome, but there is a 20% risk of septo‐optic dysplasia in the neonate.
Much faster cross‐validation in PLSR‐modelling by avoiding redundant calculations
Authors: Liland Kristian Hovde , Stefansson Petter , Indahl Ulf Geir
Published: February 2020

A novel formulation of the wide kernel algorithm for partial least squares regression (PLSR) is proposed. We show how the elimination of redundant calculations in the traditional applications of PLSR helps in speeding up any choice of cross‐validation strategy by utilizing precalculated lookup matrices.

The proposed lookup approach is combined with some additional computational shortcuts resulting in highly effective and numerically accurate cross‐validation results. The computational advantages of the proposed method are demonstrated by comparisons to the classical NIPALS and the bidiag2 algorithms for calculating cross‐validated PLSR models. Problems including both one and several responses, double/nested cross‐validated, and one‐vs‐all classification are among the considered applications.
A chemometric study combined with spectroscopy for the quantification of secondary structure of flagellar‐associated protein 174 (FAP174)
Authors: M. Yogesha , Rao Venkatramanan G. , Devangad Praveen , D'Souza Jacinta S. , Chidangil Santhosh
Published: February 2020

The secondary structure analyses of proteins hold immense importance in the field of protein science because it plays a vital role in its hierarchical classification. It is the most important transitional step in the prediction of the three‐dimensional structure of any protein. The aim of the current study is to quantitatively determine the secondary structure of an important ciliary protein, viz, an MYC‐binding protein‐1 (MYCBP‐1) orthologue, viz, flagellar‐associated protein 174 (FAP174) from the green alga, Chlamydomonas reinhardtii. FAP174 binds to A‐kinase anchoring protein 240 (AKAP240) and has a crucial role to play in ciliary motility. Hence, the biochemical characterization of FAP174 becomes more vital in understanding its molecular function. The accurate secondary structure of FAP174 was investigated through circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) combined with partial least square regression (PLSR) methods. The far‐UV CD spectrum of FAP174 exhibited a positive band at 192 nm and negative bands at 208 and 221 nm, whereas quantification through BeStSel web server revealed 65% α‐helix, approximately 2% of antiparallel β‐sheets, 6% of β‐turns, and 27% of unordered structures. These results were further confirmed by FTIR spectrum of FAP174 that revealed amide I and II bands at 1654 and 1547 cm−1, respectively. And the PLSR calibration models led to the quantification of the secondary structure for FAP174 protein that fairly corroborated with the values obtained by quantifying CD spectrum, these being approximately 54% α‐helix, 0% β‐sheets, approximately 12% β‐turns, and approximately 34% other structures. The recombinant FAP174 protein is therefore considerably α‐helical and has negligible or no β‐sheets.
Synthesis and Characterization of Thiophene‐based Donor–Acceptor–Donor Heptameric Ligands for Spectral Assignment of Polymorphic Amyloid‐β Deposits
Authors: Lantz Linda , Shirani Hamid , Klingstedt Therése , Nilsson K. Peter R.
Published: February 2020

Protein deposits are associated with many devastating diseases and fluorescent ligands able to visualize these pathological entities are essential. Here, we report the synthesis of thiophene‐based donor–acceptor–donor heptameric ligands that can be utilized for spectral assignment of distinct amyloid‐β (Aβ) aggregates, one of the pathological hallmarks in Alzheimer's disease. The ability of the ligands to selectively distinguish Aβ deposits was abolished when the chemical composition of the ligands was altered. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between aggregated proteinaceous species consisting of the same peptide or protein. In addition, such ligands might aid in interpreting the potential role of polymorphic Aβ deposits in the pathogenesis of Alzheimer's disease.
Boron–Nitrogen‐Doped Nanographenes: A Synthetic Tale from Borazine Precursors
Authors: Dosso Jacopo , Battisti Tommaso , Ward Benjamin D. , Demitri Nicola , Hughes Colan E. , Williams P. Andrew , Harris Kenneth D. M. , Bonifazi Davide
Published: February 2020

In this work, a comprehensive account of the authors’ synthetic efforts to prepare borazino‐doped hexabenzocoronenes by using the Friedel–Crafts‐type electrophilic aromatic substitution is reported. Hexafluoro‐functionalized aryl borazines, bearing anorthofluoride leaving group on each of the N‐ and B‐aryl rings, was shown to lead to cascade‐type electrophilic aromatic substitution events in the stepwise C−C bond formation, giving higher yields of borazinocoronenes than those obtained with borazine precursors bearing fluoride leaving groups at theorthopositions of the B‐aryl substituents. By using this pathway, an unprecedented boroxadizine‐doped PAH featuring a gulf‐type periphery could be isolated, and its structure proven by single‐crystal X‐ray diffraction analysis. Mechanistic studies on the stepwise Friedel–Crafts‐type cyclization suggest that the mechanism of the planarization reaction proceeds through extension of the π system. To appraise the doping effect of the boroxadizine unit on the optoelectronic properties of topology‐equivalent molecular graphenes, the all‐carbon and pyrylium PAH analogues, all featuring a gulf‐type periphery, were also prepared. As already shown for the borazino‐doped hexabenzocoronene, the replacement of the central benzene ring by its B3N2O congener widens the HOMO–LUMO gap and dramatically enhances the fluorescence quantum yield.
Feinstzerkleinerung von CFK‐Abfällen und Charakterisierung der Zerkleinerungsprodukte
Authors: Krampitz Thomas , Zöllner Mareen , Lieberwirth Holger , Kamptner Andre , Friedrich Jens
Published: February 2020

Die Zerkleinerung von kohlenstofffaserverstärkten Kunststoffen (CFK) stellt für fast alle Recyclingprozesse einen zentralen Prozessschritt dar. Mit der Zerkleinerung wird spezifische Oberfläche geschaffen, die insbesondere bei Feingütern als Maß für den Zerkleinerungserfolg dient. Im Artikel wird die Zerkleinerung von 1 m Kantenlänge im Aufgabegut bis auf Zielproduktgröße von kleiner 100 µm mittels einer dreistufigen Zerkleinerung aufgezeigt. Dabei wird auf die Herausforderungen bei der granulometrischen Charakterisierung der Zerkleinerungsprodukte und die damit verbundene Bewertung des Zerkleinerungserfolges gezielt eingegangen.
High‐temperature CO2 adsorption over Li4SiO4 sorbents derived from different lithium sources
Authors: Fang Yuan , Zou Renjie , Chen Xiaoxiang
Published: February 2020

Li4SiO4 is a promising sorbent for high temperature CO2 capture. It could be synthesized from three different Li sources (LiNO3, LiOH, and Li2CO3) by using the solid state reaction method. The effects of Li sources on the structure and CO2 adsorption/desorption properties of Li4SiO4 sorbents were analyzed in this work. The results showed that Li4SiO4 sorbents could be synthesized at a lower temperature by using LiNO3 and LiOH as the starting materials, which could reduce the sintering during the synthesis process and increase the surface area of synthesized Li4SiO4. During the CO2 adsorption/desorption cycles, Li4SiO4 sorbents derived from LiNO3 and LiOH presented higher initial CO2 adsorption capacities than those from Li2CO3. After 15 cycles, the adsorption efficiency of Li4SiO4 derived from LiNO3 showed no or slight decrease, while that from LiOH rapidly decreased to 20% of the initial value. This was because Li4SiO4 derived from LiNO3 had high surface area and porosity before CO2 adsorption/desorption cycles, and its surface area even increased after cycles. However, the surface area of Li4SiO4 derived from LiOH decreased greatly due to serious sintering. For Li4SiO4 derived from Li2CO3, its morphology and surface area were almost unchanged before and after CO2 adsorption/desorption cycles.
Biodegradable Periodic Mesoporous Organosilica (BPMO) Loaded with Daunorubicin: A Promising Nanoparticle‐Based Anticancer Drug
Authors: Mai Ngoc Xuan Dat , Birault Albane , Matsumoto Kotaro , Ta Hanh Kieu Thi , Intasa‐ard Soontaree Grace , Morrison Kendall , Thang Phan Bach , Doan Tan Le Hoang , Tamanoi Fuyuhiko
Published: February 2020

Biodegradable periodic mesoporous organosilica (BPMO) nanoparticles have emerged as a promising type of nanocarrier for drug delivery, given the biodegradable feature is advantageous for clinical translation. In this paper, we report synthesis and characterization of daunorubicin (DNR) loaded BPMO. DNR was loaded onto rhodamine B‐labeled BPMO that contain tetrasulfide bonds. Tumor spheroids and chicken egg tumor models were used to characterize the activity in biological settings. In the first experiment we examined the uptake of BPMO into tumor spheroids prepared from ovarian cancer cells. BPMO were efficiently taken up into tumor spheroids and inhibited their growth. In the chicken egg tumor model, intravenous injection of DNR‐loaded BPMO led to the elimination of ovarian tumor. Lack of adverse effect on organs such as lung appears to be due to excellent tumor accumulation of BPMO. Thus, DNR‐loaded BPMO represents a promising nanodrug compared with free DNR currently used in cancer therapy. OK
Further Investigations into Rigidity‐Activity Relationships in BisQAC Amphiphilic Antiseptics
Authors: Leitgeb Austin J. , Feliciano Javier A. , Sanchez Hugo A. , Allen Ryan A. , Morrison Kelly R. , Sommers Kyle J. , Carden Robert G. , Wuest William M. , Minbiole Kevin P. C.
Published: February 2020

Thirty‐six biscationic quaternary ammonium compounds were efficiently synthesized in one step to examine the effect of molecular geometry of two‐carbon linkers on antimicrobial activity. The synthesized compounds showed strong antimicrobial activity against a panel of both Gram‐positive and Gram‐negative bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA). While the linker geometry showed only a modest correlation with antimicrobial activity, several of the synthesized bisQACs are promising potential antiseptics due to good antimicrobial activity (MIC≤2 μM) and their higher therapeutic indices compared to previously reported QACs.
Triphenylphosphonium (TPP)‐Based Antioxidants: A New Perspective on Antioxidant Design
Authors: Wang Jiayao Y. , Li Jiaqi Q. , Xiao Yumei M. , Fu Bin , Qin Zhaohai H.
Published: February 2020

Mitochondrial oxidative damage and dysfunction contribute to a wide range of human diseases. Considering the limitation of conventional antioxidants and that mitochondria are the main source of reactive oxygen species (ROS) which induce oxidative damage, mitochondria‐targeted antioxidants which can selectively block mitochondrial oxidative damage and prevent various types of cell death have been widely developed. As a lipophilic cation, triphenylphosphonium (TPP) has been commonly used in designing mitochondria‐targeted antioxidants. Conjugated with the TPP moiety, antioxidants can achieve more than 1000‐fold higher mitochondrial concentration depending on cell membrane potentials and mitochondrial membrane potentials. Herein we discuss the deficiencies of conventional antioxidants and the advantages of mitochondrial targeting, and review various types of TPP‐based mitochondria‐targeted antioxidants. These provide theoretical and background support for the design of new anti‐oxidant.
Design, Synthesis, and Pharmacological Evaluation of First‐in‐Class Multitarget N‐Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors
Authors: Rodrigues Daniel A. , Guerra Fabiana S. , Sagrillo Fernanda S. , de Sena M. Pinheiro Pedro , Alves Marina A. , Thota Sreekanth , Chaves Lorrane S. , Sant'Anna Carlos M. R. , Fernandes Patrícia D. , Fraga Carlos A. M.
Published: February 2020

Targeting histone deacetylases (HDACs) and phosphatidylinositol 3‐kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N‐acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
A randomized, phase 1, placebo‐controlled trial of APG‐157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor‐associated microbes
Authors: Basak Saroj K. , Bera Alakesh , Yoon Alexander J. , Morselli Marco , Jeong Chan , Tosevska Anela , Dong Tien S. , Eklund Michael , Russ Eric , Nasser Hassan , Lagishetty Venu , Guo Rong , Sajed Dipti , Mudgal Sharmila , Mehta Parag , Avila Luis , Srivastava Meera , Faull Kym , Jacobs Jonathan , Pellegrini Matteo , Shin Daniel Sanghoon , Srivatsan Eri S. , Wang Marilene B.
Published: February 2020

Background

Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG‐157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target.

Methods

A double‐blind, randomized, placebo‐controlled, phase 1 clinical trial was conducted with APG‐157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity.

Results

Treatment with APG‐157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL‐1β, IL‐6, and IL‐8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T‐cell recruitment to the tumor microenvironment.

Conclusions

The results of the current study suggested that APG‐157 could serve as a therapeutic drug in combination with immunotherapy.

Lay Summary

Curcumin has been shown to suppress tumor cells because of its antioxidant and anti‐inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally.

Subjects with oral cancer were given oral APG‐157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue.

APG‐157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs.
Core needle biopsy versus incisional biopsy for differentiation of soft‐tissue sarcomas: A systematic review and meta‐analysis
Authors: Birgin Emrullah , Yang Cui , Hetjens Svetlana , Reissfelder Christoph , Hohenberger Peter , Rahbari Nuh N.
Published: February 2020

Background

Controversies exist regarding the biopsy technique of choice for the accurate diagnosis of soft‐tissue sarcoma (STS). The objective of this systematic review and meta‐analysis was to compare the diagnostic accuracy of core needle biopsy (CNB) versus incisional biopsy (IB) in STS with reference to the final histopathological result.

Methods

Studies regarding the diagnostic accuracy of CNB and IB in detecting STS were searched systematically in the MEDLINE and EMBASE databases. Estimates of sensitivity and specificity with associated 95% CIs for diagnostic accuracy were calculated. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS‐2).

Results

A total of 17 studies comprising 2680 patients who underwent 1582 CNBs and 241 IBs with subsequent tumor resection met the inclusion criteria. The sensitivity and specificity of CNB and IB to detect the dignity of lesions were 97% (95% CI, 95%‐98%) and 99% (95% CI, 97%‐99%), respectively, and 96% (95% CI, 92%‐99%) and 100% (95% CI, 94%‐100%), respectively. Estimates of the sensitivity and specificity of CNB and IB to detect the STS histotype were 88% (95% CI, 86%‐90%) and 77% (95% CI, 72%‐81%), respectively, and 93% (95% CI, 87%‐97%) and 65% (95% CI, 49%‐78%), respectively. Patients who underwent CNB had a significantly reduced risk of complications compared with patients who underwent IB (risk ratio, 0.14; 95% CI, 0.03‐0.56 [P ≤ .01). Quality assessment of studies revealed a high risk of bias.

Conclusions

CNB has high accuracy in diagnosing the dignity of lesions and STS histotype in patients with suspected STS with fewer complications compared with IB. Therefore, CNB should be regarded as the primary biopsy technique.
A comparative analysis of the dopaminergic innervation of the executive caudal nidopallium in pigeon, chicken, zebra finch, and carrion crow
Authors: von Eugen Kaya , Tabrik Sepideh , Güntürkün Onur , Ströckens Felix
Published: February 2020

Despite the long, separate evolutionary history of birds and mammals, both lineages developed a rich behavioral repertoire of remarkably similar executive control generated by distinctly different brains. The seat for executive functioning in birds is the nidopallium caudolaterale (NCL) and the mammalian equivalent is known as the prefrontal cortex (PFC). Both are densely innervated by dopaminergic fibers, and are an integration center of sensory input and motor output. Whereas the variation of the PFC has been well documented in different mammalian orders, we know very little about the NCL across the avian clade. In order to investigate whether this structure adheres to species‐specific variations, this study aimed to describe the trajectory of the NCL in pigeon, chicken, carrion crow and zebra finch. We employed immunohistochemistry to map dopaminergic innervation, and executed a Gallyas stain to visualize the dorsal arcopallial tract that runs between the NCL and the arcopallium. Our analysis showed that whereas the trajectory of the NCL in the chicken is highly comparable to the pigeon, the two Passeriformes show a strikingly different pattern. In both carrion crow and zebra finch, we identified four different subareas of high dopaminergic innervation that span the entire caudal forebrain. Based on their sensory input, motor output, and involvement in dopamine‐related cognitive control of the delineated areas here, we propose that at least three morphologically different subareas constitute the NCL in these songbirds. Thus, our study shows that comparable to the PFC in mammals, the NCL in birds varies considerably across species.
Isolation of Highly Migratory and Invasive Cells in Three‐Dimensional Gels
Authors: Takino Takahisa , Suzuki Takeshi , Seiki Motoharu
Published: February 2020

We developed a modified invasion assay in three‐dimensional (3D) gels that permits isolation of invading cells as living cells, termed an invading cell–trapping (iCT) assay. A small cell strainer consisting of nylon mesh with pores of 40‐µm square is used in this assay. A layer of gel composed of extracellular‐matrix components is formed on each side of the nylon mesh, which permits cell migration or invasion from one gel layer to the other. At the end of the assay, the two gel layers are removed from the apparatus and easily separated from each other. Invading cells from the primary gel are trapped in the secondary gel, which maintains the morphology and other properties of the invasive cells in a 3D matrix. The cells that have invaded are observed and counted with a standard light microscope without cell staining. There is no need for a specialized microscope, imaging analysis software, or advanced cell‐biological technical knowledge in this assay. This assay can also reduce measurement of nonspecific cell invasion by monitoring the upward invasion of cells. The viability of both invading and non‐invading cells trapped in the gels can be assessed by typical colorimetric assays, if desired. This assessment characterizes the total number of cells (invading and non‐invading cells) and the ratio of invading cells to total cells. By repeating the iCT assay, further enrichment of invasive and noninvasive cells can be attained. Thus, this assay improves comparative analyses between invasive and noninvasive cells. © 2020 by John Wiley & Sons, Inc.

Basic Protocol 1: Measuring upward cell invasion into collagen gel

Basic Protocol 2: Measuring cell invasion from Matrigel into collagen gel

Basic Protocol 3: Isolation and enrichment of highly invasive cells
Risk of Opioid Overdose Associated With Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population‐Based Cohort Study
Authors: Li Yan , Delcher Chris , Wei Yu‐Jung Jenny , Reisfield Gary M. , Brown Joshua D. , Tighe Patrick , Winterstein Almut G.
Published: February 2020

The recent opioid prescribing guideline cautions about the concomitant prescribing of opioids and skeletal muscle relaxants (SMRs) given the additive central nervous system depressant effect. However, the clinical relevance remains unclear. In this retrospective cohort study, we compared the risk of opioid overdose associated with concomitant use of opioids and SMRs vs. opioid use alone. Adjusted hazard ratios were 1.09 (95% confidence interval (CI), 0.74–1.62) and 1.26 (95% CI, 1.00–1.58) in the incident and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21 (95% CI, 1.00–1.48). This risk seemed to increase with treatment duration (≤ 14 days: 0.91 and 95% CI, 0.67–1.22; 15–60 days: 1.37 and 95% CI, 0.81–2.37; >60 days: 1.80 and 95% CI, 1.30–2.48) and for baclofen (1.83 and 95% CI, 1.11–3.04) and carisoprodol (1.84 and 95% CI, 1.34–2.54). Concomitant users with daily opioid dose ≥50 mg (1.50 and 95% CI, 1.18–1.92) and benzodiazepine use (1.39 and 95% CI, 1.08–1.79) also had elevated risk. Clinicians should be cautious about these potentially unsafe practices to optimize pain care and improve patient safety.
Recovery Behavior of the Luminescence Peak from Graphitic Carbon Nitride as a Function of the Synthesis Temperature
Authors: Chubenko Eugene B. , Denisov Nikita M. , Baglov Aleksey V. , Bondarenko Vitaly P. , Uglov Vladimir V. , Borisenko Viktor E.
Published: February 2020

Graphitic carbon nitride (g‐C3N4) is synthesized by thermal decomposition of thiourea and subsequent in situ polymerization of the products in the oxygen‐containing ambient at 450–625 °C and studied with scanning electron microscopy, X‐ray diffraction, energy‐dispersive X‐ray spectroscopy, Fourier‐transform infrared spectroscopy, and photoluminescence techniques. The synthesized material contains oxygen at a concentration increasing with the processing temperature from 4.8 to 9.8 at %. The photoluminescence peak is found to be red‐shifted with the temperature increased to 575 °C becoming then blue‐shifted at higher temperatures. The observed red‐shift of the photoluminescence peak is supposed to be caused by band‐gap narrowing in g‐C3N4 doped by oxygen while its recovery behavior is controlled by thermally induced oxygen‐assisted disruption of sp2 bonds in C‐N π‐orbital conjugated system of tri‐s‐triazine units building polymer sheets in g‐C3N4.
A High‐Power Aqueous Zinc–Organic Radical Battery with Tunable Operating Voltage Triggered by Selected Anions
Authors: Luo Yuwen , Zheng Feipeng , Liu Luojia , Lei Kaixiang , Hou Xuesen , Xu Gang , Meng Hui , Shi Jifu , Li Fujun
Published: February 2020

In contrast to traditional rechargeable rock‐chair metal‐ion batteries, dual‐ion batteries (DIBs) involve redox reactions with anions rather than cations in p‐type cathodes. In principle, regulating the electrochemical performance of the DIB by different anion species is highly feasible. Herein, the anion effect on the electrochemical performance of a DIB, the aqueous Zn– organic radical battery (Zn‐ORB), consisting of a poly(2,2,6,6tetramethylpiperidinyloxy‐4‐yl vinyl ether) cathode and a Zn anode, was investigated by DFT calculations. SO42−, CF3SO3−, and ClO4− with different molecular electrostatic potential values were selected as anion models. DFT calculations revealed that a stronger electrostatic interaction of the anion with the organic radical resulted in a higher operating voltage of the Zn‐ORB, which was consistent with experimental results. These results bring new insight into the redox chemistry of p‐type organic radicals with anions and will promote the development of high‐power aqueous Zn‐ORBs as well as inspire more investigations into the anion effect towards novel battery designs.
Linear distribution of capacitance in Dickson charge pumps to reduce rise time
Authors: Ballo Andrea , Grasso Alfio Dario , Palumbo Gaetano , Tanzawa Toru
Published: February 2020

This paper introduces a design strategy to reduce rise time of charge pumps maintaining equal the silicon area, which is effective when the load capacitance is lower than the total charge pump capacitance. The strategy relies on an unconventional pumping capacitors sizing, which set them not equal and follows a linear distribution. The approach is based on a theoretical analysis and is validated through post‐layout simulations using a 130‐nm complementary metal‐oxide semiconductor (CMOS) standard technology. The simulations demonstrate the advantages of the proposed design strategy and the accuracy of the theory.
A subtree‐based transformation model for cryptosystem using chaotic maps under cloud computing environment for fuzzy user data sharing
Authors: Meshram Chandrashekhar , Lee Cheng‐Chi , Ranadive Abhay S. , Li Chun‐Ta , Meshram Sarita Gajbhiye , Tembhurne Jitendra V.
Published: February 2020

Cloud computing technologies have been prospering in recent years and have opened an avenue for a wide variety of forms of adaptable data sharing. Taking advantage of these state‐of‐the‐art innovations, the cloud storage data owner must, however, use a suitable identity‐based cryptographic mechanism to ensure the safety prerequisites while sharing data to large numbers of cloud data users with fuzzy identities. As a successful way to guarantee secure fuzzy sharing of cloud data, the identity‐based cryptographic technology still faces an effectiveness problem under multireceiver configurations. The chaos theory is considered a reasonable strategy for reducing computational complexity while meeting the cryptographic protocol's security needs. In an identity‐based cryptographic protocol, public keys for individual clients are distributed, allowing the clients to separately select their own network identities or names as their public keys. In fact, in a public‐key cryptographic protocol, it is for the best that the confirmation of the public key is done in a safe, private manner, because this way the load of storage on the server's side can be considerably relieved. The objective of this paper is to outline and examine a conversion process that can transfer cryptosystems using Chebyshev's chaotic maps over the Galois field to a subtree‐based protocol in the cloud computing setting for fuzzy user data sharing, as opposed to reconcocting a different structure. Furthermore, in the design of our conversion process, no adjustment of the original cryptosystem based on chaotic maps is needed.
Insulin resistance and impaired lipid metabolism as a potential link between diabetes and Alzheimer's disease
Authors: Kulas Joshua A. , Weigel Thaddeus K. , Ferris Heather A.
Published: February 2020

Diabetes disrupts organs throughout the body including the brain. Evidence suggests diabetes is a risk factor for Alzheimer's disease (AD) and neurodegeneration. In this review, we focus on understanding how diabetes contributes to the progression of neurodegeneration by influencing several aspects of the disease process. We emphasize the potential roles of brain insulin resistance, as well as cholesterol and lipid disruption, as factors which worsen AD.
Investigating changes in estuarine ecosystem functioning under future scenarios
Authors: Hillman Jenny R. , Stephenson Fabrice , Thrush Simon F. , Lundquist Carolyn J.
Published: February 2020

Estuaries are subject to disturbance by land‐based sediment and nutrient inputs, resulting in changes to the ecosystems and the functions and services that they support. Spatial mapping tools that identify how functional hotspots in the estuary may shift in location and intensity under different disturbance scenarios highlight to managers the trajectory of change and the value of active management and restoration, but to date these tools are only available in the most intensively researched ecosystems. Using empirical data derived from long‐term monitoring and multi‐habitat field experiments we developed future scenarios representing different impacts of environmental degradation on estuarine ecosystem functions that are important for supporting ecosystem services. We used the spatial prioritization software Zonation in a novel fashion to assess effects of different disturbance scenarios on critical soft‐sediment ecosystem processes (nutrient fluxes and sediment erodibility measures) that are influenced by macrofaunal communities and local environment conditions. We compared estimates of current conditions with three scenarios linked to changes in land‐use and resulting downstream impacts on estuarine ecosystems to determine how disturbance influences the distribution of high value areas for ecosystem function. Scenarios investigated the implications of habitat degradation associated with sediment deposition and declines in large sediment‐dwelling animal abundance whose behavior has important influences on ecosystem function. Our analyses demonstrate decreases in the majority of ecosystem processes under scenarios associated with disturbances. These results suggest that it is important to restore biodiversity and ecosystem function and that the application of Zonation in this context offers a simple, rapid and cost‐effective way of identifying priority actions and locations for restoration, and how these shift due to multiple impacts.
Genomic signatures of host‐associated divergence and adaptation in a coral‐eating snail, Coralliophila violacea (Kiener, 1836)
Authors: Simmonds Sara E. , Fritts‐Penniman Allison L. , Cheng Samantha H. , Mahardika Gusti Ngurah , Barber Paul H.
Published: February 2020

The fluid nature of the ocean, combined with planktonic dispersal of marine larvae, lowers physical barriers to gene flow. However, divergence can still occur despite gene flow if strong selection acts on populations occupying different ecological niches. Here, we examined the population genomics of an ectoparasitic snail, Coralliophila violacea (Kiener 1836), that specializes on Porites corals in the Indo‐Pacific. Previous genetic analyses revealed two sympatric lineages associated with different coral hosts. In this study, we examined the mechanisms promoting and maintaining the snails’ adaptation to their coral hosts. Genome‐wide single nucleotide polymorphism (SNP) data from type II restriction site‐associated DNA (2b‐RAD) sequencing revealed two differentiated clusters of C. violacea that were largely concordant with coral host, consistent with previous genetic results. However, the presence of some admixed genotypes indicates gene flow from one lineage to the other. Combined, these results suggest that differentiation between host‐associated lineages of C. violacea is occurring in the face of ongoing gene flow, requiring strong selection. Indeed, 2.7% of all SNP loci were outlier loci (73/2,718), indicative of divergence with gene flow, driven by adaptation of each C. violacea lineage to their specific coral hosts.
Remotely sensed forest understory density and nest predator occurrence interact to predict suitable breeding habitat and the occurrence of a resident boreal bird species
Authors: Klein Julian , Haverkamp Paul J. , Lindberg Eva , Griesser Michael , Eggers Sönke
Published: February 2020

Habitat suitability models (HSM) based on remotely sensed data are useful tools in conservation work. However, they typically use species occurrence data rather than robust demographic variables, and their predictive power is rarely evaluated. These shortcomings can result in misleading guidance for conservation. Here, we develop and evaluate a HSM based on correlates of long‐term breeding success of an open nest building boreal forest bird, the Siberian jay. In our study site in northern Sweden, nest failure of this permanent resident species is driven mainly by visually hunting corvids that are associated with human settlements. Parents rely on understory nesting cover as protection against these predators. Accordingly, our HSM includes a light detection and ranging (LiDAR) based metric of understory density around the nest and the distance of the nest to the closest human settlement to predict breeding success. It reveals that a high understory density 15–80 m around nests is associated with increased breeding success in territories close to settlements (<1.5 km). Farther away from human settlements breeding success is highest at nest sites with a more open understory providing a favorable warmer microclimate. We validated this HSM by comparing the predicted breeding success with landscape‐wide census data on Siberian jay occurrence. The correlation between breeding success and occurrence was strong up to 40 km around the study site. However, the HSM appears to overestimate breeding success in regions with a milder climate and therefore higher corvid numbers. Our findings suggest that maintaining patches of small diameter trees may provide a cost‐effective way to restore the breeding habitat for Siberian jays up to 1.5 km from human settlements. This distance is expected to increase in the warmer, southern, and coastal range of the Siberian jay where the presence of other corvids is to a lesser extent restricted to settlements.
Untangling the positive association of phylogenetic, functional, and taxonomic diversity with alien bird species richness
Authors: Andrikou‐Charitidou A. , Boutsis G. , Karadimou E. , Kallimanis A. S.
Published: February 2020

Understanding the ecological mechanisms behind biological invasions remains a major focus of conservation biology and ecosystem management. Several hypotheses highlight that different facets of native biodiversity affect the establishment and spread of alien species. Here, we approach this question by examining the spatiotemporal relationship between alien bird species richness and different facets of biodiversity (taxonomic, functional, and phylogenetic) using breeding bird atlases for three U.S. states and for two time periods in each state. We associated native species richness, and functional and phylogenetic diversity with alien species richness, using generalized least squares models. Our results show that, consistently, across the three states and two time periods examined, alien species richness is positively associated with native diversity, and particularly with phylogenetic diversity. The relative importance of biodiversity metrics reflecting the functional or phylogenetic range occupied by the assemblage seems to advocate in favor of the importance of resource diversity as a main driver of both native and alien diversity. The secondary importance of biodiversity facets reflecting species functional or phylogenetic similarity, along with the lack of importance of functional or phylogenetic clustering or overdispersion, implies that if this relationship is shaped by biotic interactions, then biotic interactions facilitating coexistence (including even processes like predator‐mediated coexistence) are far more important than adversarial interactions like competition, at least at the scale of our analysis. Finally, the dominance of phylogenetic metrics over functional ones highlights the adaptive potential of a community accumulated over long lineage history may play an additional role as a source of information on evolutionary processes driving diversity patterns.
Beyond the numbers: understanding how a diversity mentoring program welcomes students into a scientific community
Authors: Ahern‐Dodson Jennifer , Clark Charlotte R. , Mourad Teresa , Reynolds Julie A.
Published: February 2020

Programs designed to broaden participation in science are often deemed “successful” based on quantitative evidence such as student participation rates, retention, and persistence. These numbers alone only explain that a program met its goals; they seldom critically explain how, specifically, the program achieved its success. To address this gap, we studied students’ perspectives about and experiences with the Ecological Society of America's award‐winning education and diversity mentoring program, Strategies for Ecology Education, Diversity and Sustainability (SEEDS). The persistence rate in ecology by SEEDS participants is three times greater than the national average, but the numbers alone do not explain the program's impact. We explored the reasons why this program has been so successful by gathering qualitative data as direct evidence explaining how SEEDS influenced participants’ decisions to study science and pursue science careers, and the resulting integration into a scientific community. We coded open‐ended survey responses from SEEDS alumni against a social influence theoretical framework that proposes three dominant processes that predict students’ integration into a scientific community: scientific self‐efficacy, scientific identity, and shared values with the scientific community. We not only found emergent evidence for all three processes, but we also gained a deeper understanding of how—in participants’ own words—SEEDS achieves its success. Specifically, SEEDS successfully welcomes students into a science community by (1) providing both breadth and depth of programming that offers flexible, multilayered approaches to developing self‐efficacy to fit the needs of diverse students, (2) enabling participants to integrate a science identity into other preexisting identities, and (3) implementing programming that intentionally helps participants to consciously connect their values with those of their communities.
Soil nutrients and precipitation are major drivers of global patterns of grass leaf silicification
Authors: Quigley Kathleen M. , Griffith Daniel M. , Donati George L. , Anderson T. Michael
Published: February 2020

Grasses accumulate high concentrations of silicon (Si) in their tissues, with potential benefits including herbivore defense, improved water balance, and reduced leaf construction costs. Although Si is one of the most widely varying leaf constituents among individuals, species, and ecosystems, the environmental forces driving this variation remain elusive and understudied. To understand relationships between environmental factors and grass Si accumulation better, we analyzed foliar chemistry of grasses from 17 globally distributed sites where nutrient inputs and grazing were manipulated. These sites span natural gradients in temperature, precipitation, and underlying soil properties, which allowed us to assess the relative importance of soil moisture and nutrients across variation in climate. Foliar Si concentration did not respond to large mammalian grazer exclusion, but significant variation in herbivore abundance among sites may have precluded the observation of defoliation effects at these sites. However, nutrient addition consistently reduced leaf Si, especially at sites with low soil nitrogen prior to nutrient addition. Additionally, a leaf‐level trade‐off between Si and carbon (C) existed that was stronger at arid sites than mesic sites. Our results suggest soil nutrient limitation favors investment in Si over C‐based leaf construction, and that fixing C is especially costly relative to assimilating Si when water is limiting. Our results demonstrate the importance of soil nutrients and precipitation as key drivers of global grass silicification patterns.
Highly Cumulated Radical Cascade Reaction of aza‐1,6‐Enyenes: Stereoselective Synthesis of exo‐Methylene Piperidines
Authors: Kamimura Akio , Itaya Tomoyuki , Yoshinaga Tatsuro , Nozawa Ryo , Kawamoto Takuji , Sumimoto Michinori , Uno Hidemitsu
Published: February 2020

Treatment of 1,6‐azaeneyne compounds with Ph3SnH resulted in the stereoselective formation of 5‐(E)‐alkylidene‐2,3‐cis‐piperidine in moderate to good yields. Intermediate products including methylenepyrrolidine and stannomethylene pyrrolidine were also detected in the reaction mixture, suggesting that the reaction progressed via a highly cumulated radical cascade process involving sequential six radical processes, i.e. radical addition, 5‐exo cyclization, substitution (1,4‐tin migration), 3‐exo cyclization, ring cleavage of cycloprolane, and hydrogen abstraction from Ph3SnH. The product distribution depended on the lower Ph3SnH concentration, resulting in higher piperidine yields. The E/Z selectivity of the exo‐methylene unit was also sensitive to the reaction temperature. The vinylic triphenyltin group was converted into hydrogen and iodine. A kinetic analysis of the reaction indicated that the 1,4‐tin migration and ring expansion progressed as irreversible reactions and that their reaction rates were large enough to progress the cascade reaction smoothly and to prevent side reactions such as hydrogen abstraction from Ph3SnH.