bluuebunny/crossref_metadata_2025 huggingface dataset:
Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology
Authors: Pradhan Shantanu , Banda Omar A. , Farino Cindy J. , Sperduto John L. , Keller Keely A. , Taitano Ryan , Slater John H.
Published: February 2020

The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.
Vision Statement: Materials in Motion
Authors: Feringa Ben L.
Published: February 2020

At the dawn of a new era of interactive and responsive materials and dynamic molecular systems there is ample opportunity to raise the level of complexity enabling mechanical motion, autonomous behavior, or interactive self‐regulatory functions. Some of the major challenges and opportunities are discussed with a brief perspective toward future developments on responsive materials.
Nanoclays‐Incorporated Thin‐Film Nanocomposite Membranes for Reverse Osmosis Desalination
Authors: Zhao Qipeng , Zhao Die Ling , Chung Tai‐Shung
Published: February 2020

A series of thin‐film nanocomposite (TFN) membranes with incorporation of Laponite nanoclays (NC‐LAP) is prepared and demonstrated for brackish water and seawater desalination. It is the first attempt to use poly(ethylene glycol) 200 (PEG200) assisted Laponite as nanofillers to improve the performance of TFN membranes for reverse osmosis (RO) seawater desalination. The influence of NC‐LAP loading and PEG200 as the dispersant on membrane properties is investigated. An increase in NC‐LAP loading results in an increase in water permeability without sacrificing the salt rejection. At the loading of 0.3 wt%, the TFN membrane shows a water permeability of 2.7 L m−2 h−1 bar−1 (LMH bar−1) and a salt rejection of 98.18% for brackish water desalination at 20 bar and 25 ± 1 °C. This water permeability is 53% higher than the conventional thin‐film composite (TFC) membrane. A steady water flux above 35 LMH is obtained when using seawater as the feed at 50 bar and 25 ± 1 °C. The existence of PEG200 to effectively disperse NC‐LAP nanoparticles is essential to fabricate the NC‐LAP incorporated TFN membranes for brackish water and seawater desalination.
Interfacial Force‐Focusing Effect in Mechanophore‐Linked Nanocomposites
Authors: Kim Tae Ann , Lamuta Caterina , Kim Hojun , Leal Cecilia , Sottos Nancy R.
Published: February 2020

Enhanced force transmission to mechanophores is demonstrated in polymer nanocomposite materials. Spiropyran (SP) mechanophores that change color and fluorescence under mechanical stimuli are functionalized at the interface between SiO2 nanoparticles and polymers. Successful mechanical activation of SP at the interface is confirmed in both solution and solid states. Compared with SP‐linked in bulk polymers, interfacial activation induces greater conversion of SP to its colored merocyanine form and also significantly decreases the activation threshold under tension. Experimental observations are supported by finite element simulation of the interfacial stress state. The interfacial force‐focusing strategy opens a new way to control the reactivity of mechanophores and also potentially indicates interfacial damage in composite materials.
Electrical and Elastic Properties of Individual Single‐Layer Nb4C3Tx MXene Flakes
Authors: Lipatov Alexey , Alhabeb Mohamed , Lu Haidong , Zhao Shuangshuang , Loes Michael J. , Vorobeva Nataliia S. , Dall'Agnese Yohan , Gao Yu , Gruverman Alexei , Gogotsi Yury , Sinitskii Alexander
Published: February 2020

2D carbides and nitrides (MXenes) are widely recognized for their exceptional promise for numerous applications. However, physical property measurements of their individual monolayers remain very limited despite their importance for revealing the intrinsic physical properties of MXenes. The first mechanical and electrical measurements of individual single‐layer flakes of Nb4C3Tx MXene, which are prepared via an improved synthetic method are reported. Characterization of field‐effect transistor devices based on individual single‐layer Nb4C3Tx flakes shows an electrical conductivity of 1024 ± 165 S cm−1, which is two orders of magnitude higher than the previously reported values for bulk Nb4C3Tx assemblies, and an electron mobility of 0.41 ± 0.27 cm2 V−1 s−1. Atomic force microscopy nanoindentation measurements of monolayer Nb4C3Tx membranes yield an effective Young's modulus of 386 ± 13 GPa, assuming a membrane thickness of 1.26 nm. This is the highest value reported for nanoindentation measurements of solution‐processable 2D materials, revealing the potential of Nb4C3Tx as a primary component for various mechanical applications. Finally, the agreement between the mechanical properties of 2D Nb4C3Tx MXene and cubic NbC suggests that the extensive experimental data on bulk carbides could be useful for identifying new MXenes with improved functional characteristics.
Straw strip mulching affects soil moisture and temperature for potato yield in semiarid regions
Authors: Chang Lei , Han Fanxiang , Chai Shouxi , Cheng Hongbo , Yang Delong , Chen Yuzhang
Published: February 2020

Straw mulching is widely used in agriculture to conserve soil water and improve crop productivity. The effects of straw strip mulching and film mulching on dryland soil water storage and temperature, potato (Solanum tuberosum L.) growth and yield, and water use efficiency (WUE) were examined from 2014 to 2015 in the rainfed semi‐arid regions of China. Field experiments were conducted with four treatments: (a) alternating strips mulched with maize (Zea mays L.) straw and bare plots with no ridges (SM); (b) alternating large ridges and small furrows with only the ridges mulched with black polyethylene film (PMP); (c) alternating narrows and wide ridges both mulched by black polyethylene film (PMF), and (d) traditional bare land planting without mulching (CK). The results indicated that film mulching had positive effects on soil water storage at the early stage of potato growth, while the SM significantly improved soil water storage at the late growth stage. Soil water storage (0–2‐m depth) was 11.3–35.4 mm greater with the SM than that with the other treatments, especially during the tuber bulking in summer drought period. Compared with the CK, the SM significantly decreased soil temperature by 0.8–1.4°C, and increased potato yield by 10.5–34.2%, WUE by 8.9–29.8%, and commodity rate by 14.7–38.8%. Compared with the PMP and PMF, the SM increased potato yield by 4.6–12.9 and 3.4–9.3%, respectively. This might be contributed to increased soil moisture and lower soil temperature, which promoted potato growth, yield, and commodity rates.
Highly Efficient Conversion of Propargylic Amines and CO2 Catalyzed by Noble‐Metal‐Free [Zn116] Nanocages
Authors: Cao Chun‐Shuai , Xia Shu‐Mei , Song Zhen‐Jun , Xu Hang , Shi Ying , He Liang‐Nian , Cheng Peng , Zhao Bin
Published: February 2020

The reaction of propargylic amines and CO2 can provide high‐value‐added chemical products. However, most of catalysts in such reactions employ noble metals to obtain high yield, and it is important to seek eco‐friendly noble‐metal‐free MOFs catalysts. Here, a giant and lantern‐like [Zn116] nanocage in zinc‐tetrazole 3D framework [Zn22(Trz)8(OH)12(H2O)9⋅8 H2O]n Trz=(C4N12O)4− (1) was obtained and structurally characterized. It consists of six [Zn14O21] clusters and eight [Zn4O4] clusters. To our knowledge, this is the highest‐nuclearity nanocages constructed by Zn‐clusters as building blocks to date. Importantly, catalytic investigations reveal that 1 can efficiently catalyze the cycloaddition of propargylic amines with CO2, exclusively affording various 2‐oxazolidinones under mild conditions. It is the first eco‐friendly noble‐metal‐free MOFs catalyst for the cyclization of propargylic amines with CO2. DFT calculations uncover that ZnII ions can efficiently activate both C≡C bonds of propargylic amines and CO2 by coordination interaction. NMR and FTIR spectroscopy further prove that Zn‐clusters play an important role in activating C≡C bonds of propargylic amines. Furthermore, the electronic properties of related reactants, intermediates and products can help to understand the basic reaction mechanism and crucial role of catalyst 1.
Targeted somatic mutagenesis through CRISPR/Cas9 ribonucleoprotein complexes in the olive fruit fly, Bactrocera oleae
Authors: Meccariello Angela , Tsoumani Konstantina T. , Gravina Andrea , Primo Pasquale , Buonanno Martina , Mathiopoulos Kostas D. , Saccone Giuseppe
Published: February 2020

The olive fruit fly, Bactrocera oleae (Diptera: Tephritidae), is the most destructive insect pest of olive cultivation, causing significant economic and production losses. Here, we present the establishment of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 methodology for gene disruption in this species. We performed targeted mutagenesis of the autosomal gene white (Bo‐we), by injecting into early embryos in vitro preassembled and solubilized Cas9 ribonucleoprotein complexes loaded with two gene‐specific single‐guide RNAs. Gene disruption of Bo‐we led to somatic mosaicism of the adult eye color. Large eye patches or even an entire eye lost the iridescent reddish color, indicating the successful biallelic mutagenesis in somatic cells. Cas9 induced either indels in each of the two simultaneously targeted Bo‐we sites or a large deletion of the intervening region. This study demonstrates the first efficient implementation of the CRISPR/Cas9 technology in the olive fly, providing new opportunities towards the development of novel genetic tools for its control.
Metal abundances in the MACER simulations of the hot interstellar medium
Authors: Pellegrini Silvia , Gan Zhaoming , Ostriker Jeremiah P. , Ciotti Luca
Published: February 2020

Hot plasma is the dominant phase of the interstellar medium of early‐type galaxies. It can originate from stellar mass losses, residual gas from the formation epoch, and accretion from outside the galaxies. Its evolution is linked to the dynamical structure of the host galaxy, to the supernova and active galactic nuclei (AGN) feedback, and to (late‐epoch) star formation in a way that has yet to be fully understood. Important clues about the origin and evolution of the hot gas come from the abundances of heavy metals that have been studied with increasing detail through XMM‐Newton and Chandra. We present recent high‐resolution hydrodynamical simulations of the hot gas evolution that include the above processes, where several chemical species, originating in asymptotic giant branch stars and supernovae of types Ia and II, have also been considered. The high resolution, of few parsecs in the central galactic region, allows us to track the metal enrichment, transportation, and dilution throughout the galaxy. The comparison of model results with observed abundances demonstrates good agreement for the region enriched by the AGN wind but also shows discrepancies for the diffuse hot gas; the latter indicates the need for a revision of standard assumptions and/or the importance of neglected effects due to the dust and/or residual uncertainties in deriving abundances from the X‐ray spectra.
MXene‐Based Anodes for Metal‐Ion Batteries
Authors: Greaves Michael , Barg Suelen , Bissett Mark A.
Published: February 2020

Invited for this month's cover picture is the group of Dr. Suelen Barg and Dr. Mark A. Bissett from the University of Manchester (U.K). The cover picture shows a schematic of how 2D layered materials such as MXenes can be used as anodes for the intercalation of metal ions for use in energy storage applications such as batteries. These novel materials are attracting great interest for energy storage applications and in this Review we summarise the state of the field and future directions. Read the full text of the Review at 10.1002/batt.201900165.
The association between risky decision making and attention‐deficit/hyperactivity disorder symptoms: A preregistered assessment of need for cognition as underlying mechanism
Authors: Zadelaar Jacqueline N. , Dekkers Tycho J. , Huizenga Hilde M.
Published: February 2020

Attention‐Deficit/Hyperactivity Disorder (ADHD) is related to suboptimal decision making in experimental tasks and to real‐life risk‐taking behavior (RTB) such as substance abuse and unsafe traffic conduct. In this preregistered study, we tested whether these associations are mediated by need for cognition—the extent to which one tends towards, and enjoys, analytical thought. In a large sample of young adults (N = 463, Mage = 19.7 years), we tested whether need for cognition mediated the association between self‐reported ADHD symptoms on the one hand and decision‐making strategy complexity on an experimental gambling task and self‐reported real‐life RTB on the other hand. Preregistered confirmatory analyses indicated first that ADHD symptoms were positively associated with real‐life RTB, but the association was not mediated by need for cognition. Second, ADHD symptoms were not related to decision‐making strategy complexity, and need for cognition was not a significant mediator. Explorative analyses revealed that (a) need for cognition was associated with higher decision‐making accuracy and slower reaction time; (b) need for cognition was related to inattentive but not to hyperactive/impulsive ADHD symptoms; (c) need for cognition was associated with health‐related RTB but not interpersonal RTB; and (4) only the association between inattention and health‐related RTB was mediated by need for cognition. We conclude that need for cognition is not a mediator in the association between ADHD symptoms and RTB. Additionally, we conclude that neither ADHD symptoms nor need for cognition predict decision‐making strategy complexity. Implications for both future research and clinical practice are discussed.
Sequential boost of intensity‐modulated radiotherapy with chemotherapy for inoperable esophageal squamous cell carcinoma: A prospective phase II study
Authors: Fan Xing‐Wen , Wang Hong‐Bing , Mao Jing‐Fang , Li Ling , Wu Kai‐Liang
Published: February 2020

Purpose

This prospective phase II study aimed to determine the efficacy and tolerability of sequential boost of intensity‐modulated radiation therapy (IMRT) with chemotherapy for patients with inoperable esophageal squamous cell carcinoma (ESCC).

Methods

Patients with histologically or cytologically proven inoperable ESCC were enrolled in this study (ChiCTR‐OIC‐17010485). A larger target volume for subclinical lesion was irradiated with 50 Gy, and then, a smaller target volume only including gross tumor was boosted to 66 Gy. The fraction dose was 2 Gy, and no elective node was irradiated. Concurrent and consolidation chemotherapy of fluorouracil (600 mg/m2, days 1‐3) plus cisplatin (25 mg/m2, days 1‐3) was administered every 4 weeks, for 4 cycles in total. The primary endpoint was 2‐year progression‐free survival (PFS).

Results

Eighty‐eight patients were enrolled in this study. The median age was 65 years (range: 45‐75 years), and 69 patients (78.4%) were men. With the median follow‐up of 26 (range: 3‐95) months, the 2‐ and 5‐year PFS were 39.3% and 36.9%, respectively, and overall survival (OS) were 57.1% and 39.2%, respectively. Tumor stage and concurrent chemotherapy were independent OS predictors. Major acute adverse events were myelosuppression and esophagitis, most of which were grades 1‐2. Nine percent and 2.3% of patients had grade 3 acute esophagitis and late esophageal strictures, respectively.

Conclusions

Sequential boost to 66 Gy by IMRT with chemotherapy was safe and effective for inoperable ESCC. A randomized phase III study to compare with standard dose of 50 Gy is warranted.
Blastomycosis presenting as an isolated progressive painless verrucous skin lesion
Authors: Butt Saira
Published: February 2020

A painless progressive verrucous skin plaque in an endemic area should raise suspicion for blastomycosis resulting in prompt biopsy with fungal stains and culture. Skin is a common extrapulmonary site. Itraconazole is treatment of choice.
A “happy ending” of mediastinal and abdominal lymphadenopathy associated with hepatosplenomegaly and pulmonary lesions
Authors: Ben Salem Fares , Triki Wafa , Belkhir Asma , Sbaihi Siwar , Boukriba Seif
Published: February 2020

Major diagnosis for mediastinal and abdominal lymphadenopathy is lymphoma and tuberculosis. Spontaneous remarkable evolution should discuss viral infection on the condition that no corticosteroids have been taken before as they could magically improve an authentic lymphoma. Trial of antituberculosis treatment that is used in some cases could lead to a misdiagnosis as the viral‐infected patient can spontaneously heal as it is described in this case.
Separate Sets of Mutations Enhance Activity and Substrate Scope of Amine Dehydrogenase
Authors: Franklin Robert D. , Mount Conner J. , Bommarius Bettina R. , Bommarius Andreas S.
Published: February 2020

Mutations were introduced into the leucine amine dehydrogenase (L‐AmDH) derived from G. stearothermophilus leucine dehydrogenase (LeuDH) with the goals of increased activity and expanded substrate acceptance. A triple variant (L‐AmDH‐TV) including D32A, F101S, and C290V showed an average of 2.5‐fold higher activity toward aliphatic ketones and an 8.0 °C increase in melting temperature. L‐AmDH‐TV did not show significant changes in relative activity for different substrates. In contrast, L39A, L39G, A112G, and T133G in varied combinations added to L‐AmDH‐TV changed the shape of the substrate binding pocket. L‐AmDH‐TV was not active on ketones larger than 2‐hexanone. L39A and L39G enabled activity for straight‐chain ketones as large as 2‐decanone and in combination with A112G enabled activity toward longer branched ketones including 5‐methyl‐2‐octanone.
FOx News: Towards Methanol‐driven Biocatalytic Oxyfunctionalisation Reactions
Authors: Willot Sébastien J.‐P. , Hoang Manh Dat , Paul Caroline E. , Alcalde Miguel , Arends Isabel W. C. E. , Bommarius Andreas S. , Bommarius Bettina , Hollmann Frank
Published: February 2020

The novel formate oxidase from Aspergillus oryzae (AoFOx) is a useful catalyst to promote H2O2‐dependent oxyfunctionalisation reactions. In this contribution we exploit the substrate promiscuity of AoFOx to fully oxidise methanol and formaldehyde to CO2 and drive peroxygenase‐catalysed stereoselective oxyfunctionalisation reactions. The highly atom efficient H2O2 generation system also enabled high catalytic turnover of the peroxygenase production enzyme.
Scalable Hybrid Synthetic/Biocatalytic Route to Psilocybin
Authors: Fricke Janis , Kargbo Robert , Regestein Lars , Lenz Claudius , Peschel Gundela , Rosenbaum Miriam A. , Sherwood Alexander , Hoffmeister Dirk
Published: February 2020

Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment‐resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis with the mushroom kinase PsiK. This enzyme was biochemically characterized and used to produce one gram of psilocybin from psilocin within 20 minutes. We also describe a pilot‐scale protocol for recombinant PsiK that yielded 150 mg enzyme in active and soluble form. Our work consolidates the simplicity of tryptamine chemistry with the specificity and selectivity of enzymatic catalysis and helps provide access to an important drug at potentially reasonable cost.
Ming‐Phos/Gold(I)‐Catalyzed Stereodivergent Synthesis of Highly Substituted Furo[3,4‐d][1,2]oxazines†
Authors: Zhou Lujia , Xu Bing , Ji Danting , Zhang Zhan‐Ming , Zhang Junliang
Published: February 2020

Summary of main observation and conclusion

A gold(I)‐catalyzed asymmetric intermolecular tandem [3+3]‐cyclization reaction of 2‐(1‐alkynyl)‐2‐ alken‐1‐ones with nitrones has been developed by using Ming‐Phos as a chiral ligand. This method enables access to the stereodivergent synthesis of highly substituted furo[3,4‐d][1,2]oxazines in excellent efficiency and stereoselectivity (up to 99% yield, 99% ee, >20 : 1 dr).
Significance of minimal residual disease monitoring by real‐time quantitative polymerase chain reaction in core binding factor acute myeloid leukemia for transplantation outcomes
Authors: Yalniz Fevzi F. , Patel Keyur P. , Bashir Qaiser , Marin David , Ahmed Sairah , Alousi Amin M. , Chen Julianne , Ciurea Stefan O. , Rezvani Katy , Popat Uday R. , Shpall Elizabeth J. , Champlin Richard E. , Oran Betül
Published: February 2020

Background

Despite the well‐defined role of minimal residual disease (MRD) monitoring by real‐time quantitative polymerase chain reaction (RT‐PCR) for RUNX1/RUNX1T1 and CBFB‐MYH11 transcripts in core binding factor (CBF) acute myeloid leukemia (AML) after intensive chemotherapy, there has been a paucity of data assessing the utility of MRD monitoring at and after allogeneic hematopoietic stem cell transplantation (HSCT).

Methods

Patients with CBF AML who underwent HSCT in complete remission (first or second) from January 2007 through December 2018 were included in this analysis.

Results

MRD by polymerase chain reaction at HSCT was assessed in 50 of 76 patients, and 44 (88%) had evidence of MRD (MRDpos). MRDpos patients had 3‐year overall survival (OS) and leukemia‐free survival (LFS) rates of 69.3% and 66.3%, respectively. Six MRD‐negative patients had 3‐year OS and LFS rates of 100% and 100%, respectively. Thirty‐five of the 70 evaluable patients (50%) had a day +100 MRD assessment by RT‐PCR, and 14 (40%) were MRDpos. The presence of MRD by RT‐PCR on day +100 was not associated with lower estimates of LFS (75% vs 82.2%; P = .3) but was associated with a higher relapse incidence, although the difference did not reach statistical significance (27.6% vs 9.7%; P = .2).

Conclusions

Durable complete remissions can be achieved in patients with CBF AML with HSCT even if they are MRDpos by RT‐PCR at HSCT. The clinical impact of frequent MRD monitoring for identifying a group at high risk for early relapse and then for determining the best time point for therapeutic interventions to prevent impending relapse warrants investigation in prospectively designed clinical trials.
Intermolecular Interactions between Halogen‐Substituted p‐Benzoquinones and Halide Anions: Anion‐π Complexes versus Halogen Bonding
Authors: Jalilov Almaz , Deats Spencer , Albukhari Muath , Zeller Matthias , Rosokha Sergiy V.
Published: February 2020

Intermolecular interactions between halo‐substituted p‐benzoquinones (BQ) and halide anions were examined in solution, solid‐state and/or in silico. While X‐ray crystallography revealed only halogen bonding (XB) between tetraiodo‐p‐benzoquinone (I4Q) and halides, the results of a UV‐Vis study in solutions were consistent with the formation of 1 : 1 anion‐π complexes. DFT computations showed that the anion‐π complexes of halides with most halo‐substituted BQ molecules were more stable (by 2–7 kcal/mol) than their XB analogues, but the stabilities of different complexes of I4Q were essentially the same. Thus, the structural features of the co‐crystals with I4Q were related to multicenter XB interactions between BQs and halides, thus leading to the formation of 3D networks. The observation of anion‐π complexes in solutions was attributed to their higher molar absorptivity (by more than an order of magnitude) than that of their XB analogues. Overall, the stabilities of anion‐π and XB complexes between BQs and halides were well correlated with the values of highest electrostatic potentials on the surfaces of BQ molecules when their polarizations were taken into account.
A hybrid fluid–kinetic neutral model based on a micro–macro decomposition in the SOLPS‐ITER plasma edge code suite
Authors: Horsten N. , Dekeyser W. , Blommaert M. , Samaey G. , Baelmans M.
Published: February 2020

We present a hybrid fluid–kinetic model for the hydrogenic atoms in the plasma edge that is implemented in SOLPS‐ITER. A micro–macro decomposition of the kinetic equation leads to a fluid model with a continuity and parallel momentum equation (implemented in B2.5) coupled to a kinetic correction equation (implemented in EIRENE). We assess the hybrid model for a high recycling fixed background plasma. The hybrid approach leads to a reduction of the Central Processing Unit(CPU) time required to obtain the same statistical error as the full kinetic Monte Carlo (MC) simulation with approximate factors of 1.7, 4.9, and 1.9 for the particle, parallel momentum, and electron energy source, respectively. However, there is an increase in CPU time for the ion energy source. By comparing the results with our in‐house plasma edge code, we conclude that the hybrid performance can be improved by adapting some default MC features in EIRENE.
Learning Pathway Dynamics from Single‐Cell Proteomic Data: A Comparative Study
Authors: Verrou Kleio‐Maria , Tsamardinos Ioannis , Papoutsoglou Georgios
Published: February 2020

Single‐cell platforms provide statistically large samples of snapshot observations capable of resolving intrercellular heterogeneity. Currently, there is a growing literature on algorithms that exploit this attribute in order to infer the trajectory of biological mechanisms, such as cell proliferation and differentiation. Despite the efforts, the trajectory inference methodology has not yet been used for addressing the challenging problem of learning the dynamics of protein signaling systems. In this work, we assess this prospect by testing the performance of this class of algorithms on four proteomic temporal datasets. To evaluate the learning quality, we design new general‐purpose evaluation metrics that are able to quantify performance on (i) the biological meaning of the output, (ii) the consistency of the inferred trajectory, (iii) the algorithm robustness, (iv) the correlation of the learning output with the initial dataset, and (v) the roughness of the cell parameter levels though the inferred trajectory. We show that experimental time alone is insufficient to provide knowledge about the order of proteins during signal transduction. Accordingly, we show that the inferred trajectories provide richer information about the underlying dynamics. We learn that established methods tested on high‐dimensional data with small sample size, slow dynamics, and complex structures (e.g. bifurcations) cannot always work in the signaling setting. Among the methods we evaluate, Scorpius and a newly introduced approach that combines Diffusion Maps and Principal Curves were found to perform adequately in recovering the progression of signal transduction although their performance on some metrics varies from one dataset to another. The novel metrics we devise highlight that it is difficult to conclude, which one method is universally applicable for the task. Arguably, there are still many challenges and open problems to resolve. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
Synthesis of C37‐Alkenones for Past Climate Reconstructions
Authors: Berton Giacomo , Pizzini Sarah , Fabris Fabrizio , Bertolin Tommaso , Pafumi Eugenia , Ceccon Leonardo , Daelemans Jonas , Borsato Giuseppe , Scarso Alessandro , Piazza Rossano , Ferretti Patrizia
Published: February 2020

The total syntheses of three C37 methyl‐alkenones with different degrees of unsaturation and of their 13C‐labelled analogues from commercially available starting materials are presented herein for the first time. These molecules are important to improve the reliability of the measurements and reconstructions of the sea surface temperature and salinity.
Identification of cyberbullying on multi‐modal social media posts using genetic algorithm
Authors: Kumari Kirti , Singh Jyoti Prakash
Published: February 2020

Cyberbullying is one of the detrimental effects, social media is facing nowadays. With the increasing use of photo sharing and text comments, the severity of cyberbullying has increased many folds. Automated tools to detect these events have become necessary to make this platform healthy and secure. Sometimes innocent‐looking images and text also convey bullying messages when posted together. So, the separate systems for processing text and images may not work properly to identify all cases of cyberbullying. In this research, we have tried to extract combined features of text and images to identify different cases of cyberbullying. We used a pre‐trained VGG‐16 network and convolutional neural network to extract the features from images and text, respectively. These features are further optimized using genetic algorithm to increase the efficiency of the whole system. Our proposed model is validated with a dataset containing text and image to achieve an F1‐score 78% which shows an improvement of 9% over earlier reported results on the same dataset.
Permian lateral crustal growth and reworking along the Solonker suture zone (North China) constrained by high εHf(t) igneous rocks
Authors: Gao Zhengxi , Li Yinglei , Wang Jichun , Song Chongyu , Wang Jingfan , Zhang Jiadong , Zhang Zhanfei , Xu Zhan , Xiao Jianwei
Published: February 2020

High εHf(t) intermediate‐felsic rocks have been found in some world‐famous orogenic belts and are considered as one useful proxy for modelling crustal growth. In contrast, low εHf(t) felsic rocks are generally derived from reworked ancient crust. In this study, we identified some Permian high zircon εHf(t) andesite, rhyolite, granodiorite and quartz diorite along the Solonker suture zone. The andesite (270 ± 3 Ma) shows high‐zircon εHf(t) (+4.7 to +7.9) and high‐Mg (Mg#= 42–75) values, high Sr contents (263–401 ppm) and Sr/Y ratios (13–24), akin to typical high‐Mg andesite, and are derived from a metasomatised source modified by the slab‐derived fluid/melt. The rhyolites (282 ± 2 Ma and 279 ± 2 Ma) show positive εHf(t) values (+3.4 to +14.9) and I‐type granite affinity. The granodiorite (295 ± 3 Ma) and quartz diorite (285 ± 1 Ma) are also characterised by high εHf(t) values, high‐K calc‐alkaline and I‐type granitoid compositions, but high A/CNK values (1.08–1.47) and CIPW‐normative corundum (1.61–5.56 vol%), due to late‐alteration induced low Na2O + K2O contents. The I‐type rhyolite and granitoid may have been formed by dehydration melting of sub‐alkaline meta‐basalts (mafic lower crust). The high‐Mg andesite, I‐type rhyolite and granitoids in this study were generated in a continental arc setting related to the Permian divergent double subduction of the Paleo‐Asian Ocean. The high εHf(t) Elitu andesites represent the lateral juvenile continental crust, and high εHf(t) felsic rocks represent mafic‐lower continental crust reworking.
Analysis of new visualization techniques of left heated lid‐driven square cavity
Authors: Narayana Vekamulla
Published: February 2020

In the present study, an attempt is made to explore the flow visualization techniques inside the left‐heated lid‐driven square cavity. The governing equations along with boundary conditions are solved numerically. The simulated results (100 ≤ Re ≤ 1000 and 0.001 ≤ Ri ≤ 10) are validated with previous results in the literature. The convection differencing schemes, namely, UPWIND, QUICK, SUPERBEE, and self‐filtered central differencing are discussed and are used to simulate the flow using MPI code. It is observed that the computational cost for all the differencing schemes get reduced tremendously when the MPI code is implemented. Plots demonstrating the influences of Re and Ri in terms of the contours of the fluid streamlines, isotherms, energy streamlines, and field synergy principle are presented.
Effects of the viscous dissipation and chemical reaction on Casson nanofluid flow over the permeable stretching/shrinking sheet
Authors: Dero Sumera , Mohd Rohni Azizah , Saaban Azizan
Published: February 2020

A steady two‐dimensional Casson nanofluid flow over the permeable stretching/shrinking sheet along the viscous dissipation and the chemical reaction is studied in this article. The convective boundary condition is incorporated in energy equation. Similarity variables are applied to convert the governing partial differential equations into ordinary differential equations. The numerical solutions of the equations are obtained by using the shooting method with Maple implementation. The numerical findings indicate occurrence of the dual solutions for a certain range of stretching/shrinking and suction parameters. Therefore, a stability analysis is done to find the solution that is stable and physically realizable. The effects of the pertinent physical parameters on velocity, temperature, and concentration profiles are investigated graphically. Numerical results of various parameters involved for skin friction coefficient, the local Nusselt as well as Sherwood numbers are determined and also discussed in detail. The Casson and suction parameters decrease the velocity in the first solution, whereas they increase it in the second solution. The rate of heat transfer increases in both solutions with an increment in Eckert number, Biot number, thermophoresis, and Brownian motion parameters. Thermophoresis and Brownian motion parameters show opposite behavior in the nanoparticle's concentration. The nanoparticle concentration decreases in both solutions with increment in Schmidt number, Brownian motion, and chemical reaction parameters.
Effects of the Caputo fractional derivatives on convective flow in wavy vented enclosures filled with a porous medium using Al2O3‐Cu hybrid nanofluids
Authors: Ahmed Sameh E. , Mansour Mohamed A. , Abdel‐Salam Emad A.‐B. , Mohamed Eman F.
Published: February 2020

This paper studies the effect of fractional derivatives on the fractional convective flow of hybrid nanofluids in a wavy enclosure that has inlet and outlet parts near the left wall and is filled with a porous medium. The Caputo definition of the fractional derivatives is applied on the partial differential equations governing flow. The complex shape is mapped to a rectangular domain using appropriate transformations. The finite difference method is used to solve the resulting system. The results showed that an increase in order of the fractional derivatives causes a low activity of the fluid flow and a reduction in the rate of heat transfer. Also, an increase in the nanoparticles volume fractions reduces the activity of the fluid flow and, as a result, the rate of heat transfer is diminished. An enhancement in fluid motion and rate of the heat transfer is obtained by increasing the amplitude of the wavy wall.
Methodologies and Management Framework for Restoration of Wetland Hydrologic Connectivity: A Synthesis
Authors: Meng Bo , Liu Jing-ling , Bao Kun , Sun Bin
Published: February 2020

Under the dual influences of high-intensity anthropogenic activity and climate change, wetland hydrologic connectivity (HC) has decreased significantly, resulting in the severe fragmentation of wetlands, a decrease in wetland area, and a degradation of hydrological functions, resulting in a worsening disaster response to floods and droughts. Dynamic changes in wetland HC are affected by a variety of factors. Many degraded wetlands have undergone measures to restore HC. Recovery can improve the HC pattern of degraded wetlands. Based on the knowledge of practitioners and a review of the literature, it was found that recovery measures can be divided into structural recovery and functional recovery according to the specific recovery objectives. However, the current recovery method lacks a holistic analysis of the HC pattern. To this end, we propose a hydrologic network–water balance-based HC recovery and management framework that overcomes the limitations of single-drive-factor repair and local repair effects. Integr Environ Assess Manag 2020;16:438–451. © 2020 SETAC
Emerging roles of the αC‐β4 loop in protein kinase structure, function, evolution, and disease
Authors: Yeung Wayland , Ruan Zheng , Kannan Natarajan
Published: February 2020

The faithful propagation of cellular signals in most organisms relies on the coordinated functions of a large family of protein kinases that share a conserved catalytic domain. The catalytic domain is a dynamic scaffold that undergoes large conformational changes upon activation. Most of these conformational changes, such as movement of the regulatory αC‐helix from an “out” to “in” conformation, hinge on a conserved, but understudied, loop termed the αC‐β4 loop, which mediates conserved interactions to tether flexible structural elements to the kinase core. We previously showed that the αC‐β4 loop is a unique feature of eukaryotic protein kinases. Here, we review the emerging roles of this loop in kinase structure, function, regulation, and diseases. Through a kinome‐wide analysis, we define the boundaries of the loop for the first time and show that sequence and structural variation in the loop correlate with conformational and regulatory variation. Many recurrent disease mutations map to the αC‐β4 loop and contribute to drug resistance and abnormal kinase activation by relieving key auto‐inhibitory interactions associated with αC‐helix and inter‐lobe movement. The αC‐β4 loop is a hotspot for post‐translational modifications, protein–protein interaction, and Hsp90 mediated folding. Our kinome‐wide analysis provides insights for hypothesis‐driven characterization of understudied kinases and the development of allosteric protein kinase inhibitors.
Wide‐field monitoring and real‐time local recording of microvascular networks on small animals with a dual‐raster‐scanned photoacoustic microscope
Authors: Yang Fei , Wang Zhiyang , Zhang Wuyu , Ma Haigang , Cheng Zhongwen , Gu Ying , Qiu Haixia , Yang Sihua
Published: February 2020

Abstact

Photoacoustic microscopy (PAM) provides a new method for the imaging of small‐animals with high‐contrast and deep‐penetration. However, the established PAM systems have suffered from a limited field‐of‐view or imaging speed, which are difficult to both monitor wide‐field activity of organ and record real‐time change of local tissue. Here, we reported a dual‐raster‐scanned photoacoustic microscope (DRS‐PAM) that integrates a two‐dimensional motorized translation stage for large field‐of‐view imaging and a two‐axis fast galvanometer scanner for real‐time imaging. The DRS‐PAM provides a flexible transition from wide‐field monitoring the vasculature of organs to real‐time imaging of local dynamics. To test the performance of DRS‐PAM, clear characterization of angiogenesis and functional detail was illustrated, hemodynamic activities of vasculature in cerebral cortex of a mouse were investigated. Furthermore, response of tumor to treatment were successfully monitored during treatment. The experimental results demonstrate the DRS‐PAM holds the great potential for biomedical research of basic biology.
Neuropeptide Y Acts Directly on Cartilage Homeostasis and Exacerbates Progression of Osteoarthritis Through NPY2R
Authors: Kang Xiaomin , Qian Zhuang , Liu Jiali , Feng Dongxu , Li Huixia , Zhang Zhuanmin , Jin Xinxin , Ma Zhengmin , Xu Mao , Li Fang , Zhang Ying , Gao Xin , Sun Hongzhi , Wu Shufang
Published: February 2020

Neuropeptide Y (NPY) is known to regulate bone homeostasis; however, its functional role as a risk factor during osteoarthritis (OA) remains elusive. In this study, we aim to investigate the direct effect of NPY on degradation of cartilage and progression of OA and explore the molecular events involved. NPY was overexpressed in human OA cartilage accompanied with increased expression of NPY1 receptor (NPY1R) and NPY2 receptor (NPY2R). Stressors such as cold exposure resulted in the peripheral release of NPY from sympathetic nerves, which in turn promoted upregulation of NPY and NPY2R in articular cartilage in vivo. Intra-articular administration of NPY significantly promoted chondrocyte hypertrophy and cartilage matrix degradation, with a higher OARSI score than that of control mice, whereas inhibition of NPY2R but not NPY1R with its specific antagonist remarkably ameliorated NPY-mediated effects. Moreover, NPY activated mTORC1 pathway in articular chondrocytes, whereas the administration of rapamycin (an mTORC1 inhibitor) in vitro abrogated NPY-mediated effects. Mechanistically, mTORC1 downstream kinase S6K1 interacted with and phosphorylated SMAD1/5/8 and promoted SMAD4 nuclear translocation, resulting in upregulation of Runx2 expression to promote chondrocyte hypertrophy and cartilage degradation. In conclusion, our findings provided the direct evidence and the crucial role of NPY in cartilage homeostasis. © 2020 American Society for Bone and Mineral Research.
Extension of the fast multipole method for the rectangular cells with an anisotropic partition tree structure
Authors: Andoh Yoshimichi , Yoshii Noriyuki , Okazaki Susumu
Published: February 2020

The fast multipole method (FMM) is an order N method for the numerically rigorous calculation of the electrostatic interactions among point charges in a system of interest. The FMM is utilized for massively parallelized software for molecular dynamics (MD) calculations. However, an inconvenient limitation is imposed on the implementation of the FMM: In three‐dimensional case, a cubic MD unit cell is hierarchically divided by the octree partitioning under isotropic periodic boundary conditions along three axes. Here, we extended the FMM algorithm adaptive to a rectangular MD unit cell with different periodicity along the axes by applying an anisotropic hierarchical partitioning. The algorithm was implemented into the parallelized general‐purpose MD calculation software designed for a system with uniform distribution of point charges in the unit cell. The partition tree can be a mixture of binary and ternary branches, the branches being chosen arbitrarily with respect to the coordinate axes at any levels. Errors in the calculated electrostatic interactions are discussed in detail for a selected partition tree structure. The extension enables us to execute MD calculations under more general conditions for the shape of the unit cell, partition tree, and boundary conditions, keeping the accuracy of the calculated electrostatic interactions as high as that with the conventional FMM. An extension of the present FMM algorithm to other prime number branches, such as 5 and 7, is straightforward.
Effect of Drinking Oxygenated Water Assessed by in vivo MRI Relaxometry
Authors: Vatnehol Svein Are Sirirud , Hol Per Kristian , Bjørnerud Atle , Amiry‐Moghaddam Mahmood , Haglerød Camilla , Storås Tryggve Holck
Published: February 2020

Grant Support

This project was funded by the Research Council of Norway.

Background

Oxygen uptake through the gastrointestinal tract after oral administration of oxygenated water in humans is not well studied and is debated in the literature. Due to the paramagnetic properties of oxygen and deoxyhemoglobin, MRI as a technique might be able to detect changes in relaxometry values caused by increased oxygen levels in the blood.

Purpose

To assess whether oxygen dissolved in water is absorbed from the gastrointestinal tract and transported into the bloodstream after oral administration.

Study Type

A randomized, double‐blinded, placebo‐controlled crossover trial.

Population/Subjects

Thirty healthy male volunteers age 20–35.

Field Strength/Sequence

3T/Modified Look–Locker inversion recovery (MOLLI) T1‐mapping and multi fast field echo (mFFE) T2*‐mapping.

Assessment

Each volunteer was scanned in two separate sessions. T1 and T2* maps were acquired repeatedly covering the hepatic portal vein (HPV) and vena cava inferior (VCI, control vein) before and after intake of oxygenated or control water. Assessments were done by placing a region of interest in the HPV and VCI.

Statistical Test

A mixed linear model was performed to the compare control vs. oxygen group.

Results

Drinking caused a mean 1.6% 95% CI (1.1–2.0% P < 0.001) increase in T1 of HPV blood and water oxygenation attributed another 0.70% 95% confidence interval (CI) (0.07–1.3% P = 0.028) increase. Oxygenation did not change T1 in VCI blood. Mean T2* increased 9.6% 95% CI (1.7–17.5% P = 0.017) after ingestion of oxygenated water and 1.2% 95% CI (−4.3–6.8% P = 0.661) after ingestion of control water. The corresponding changes in VCI blood were not significant.

Data Conclusion

Ingestion of water caused changes in T1 and T2* of HPV blood compatible with dilution due to water absorption. The effects were enhanced by oxygen. Assessment of oxygen enrichment of HPV blood was not possible due to the dilution effect.

Level of Evidence

2

Technical Efficacy Stage

2 J. Magn. Reson. Imaging 2020;52:720–728.
Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS‐CoV‐2 infection
Authors: Xia Jianhua , Tong Jianping , Liu Mengyun , Shen Ye , Guo Dongyu
Published: February 2020

Objective

This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS–CoV‐2‐infected patients.

Methods

A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from 26 January 2020 to 9 February 2020. At an interval of 2 to 3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse‐transcription polymerase chain reaction (RT‐PCR) assay.

Results

Twenty‐one common‐type and nine severe‐type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT‐PCR results. Fifty‐eight samples from other patents were all negative.

Conclusion

We speculate that SARS‐CoV‐2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis.