bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractMutations 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

AbstractThe 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

AbstractPsilocybin, 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 conclusionA 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

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

AbstractIntermolecular 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

AbstractWe 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

AbstractSingle‐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.
Identification of cyberbullying on multi‐modal social media posts using genetic algorithm
Authors: Kumari Kirti , Singh Jyoti Prakash 
Published: February 2020

AbstractCyberbullying 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.
Analysis of new visualization techniques of left heated lid‐driven square cavity
Authors: Narayana Vekamulla 
Published: February 2020

AbstractIn 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

AbstractA 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

AbstractThis 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

Abstract
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

AbstractThe 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

AbstactPhotoacoustic 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

ABSTRACT
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

AbstractThe 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.