bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Recognition of Quaternary Ammonium Ions by Structurally Flexible Cages†
Authors: Huang Qi‐Cheng , Quan Mao , Yao Huan , Yang Liu‐Pan , Jiang Wei
Published: February 2021

Main observation and conclusion

The binding behaviors of three structurally similar and flexible cages to a series of quaternary ammonium ions have been systematically studied. The cage with phenyl sidewalls is new; moreover, its structure and conformational states have been characterized by NMR, 2D NMR, and X‐ray crystallography. The results reveal that the three cages show quite high binding affinities and selectivities to different guests. Enthalpy‐entropy compensation was invoked to explain the different binding performance. Moreover, a six‐component, high‐fidelity self‐sorting system was successfully constructed by using these cages and three guests. This suggests that conformationally flexible hosts may also achieve high binding affinities and selectivities, which is in contrast to the traditional point of view — only preorganized and rigid hosts are able to do so. This research advocates that conformational flexibility should also be seriously considered in host design.
Vinyl Groups Containing Tetraphenylethylene Derivatives as Fluorescent Probes Specific for Palladium and the Quenching Mechanism†
Authors: Liu Xiaoqing , Shang Yuxuan , Chen Zhong‐Ren
Published: February 2021

Main observation and conclusion

We previously reported that a series of tetraphenylethylene (TPE)‐containing all‐hydrocarbon conjugated polymers exhibited a specific fluorescence quenching by palladium ions (Pd2+). To understand the quenching mechanism, herein we investigate the quenching behaviors of three TPE derivatives in the presence of Pd2+. Each TPE derivative, consisting of TPE unit and terminal vinyl groups, shows an aggregation‐induced emission (AIE) and its fluorescence turns off specifically to Pd2+. The sensitivity is enhanced with increasing numbers of vinyl groups in the molecules. By time‐resolved fluorescence measurement, a dynamic quenching is observed where the fluorescence lifetime is reduced with Pd2+. Specifically, the quenching occurs via the electron transfer in the excited states, as suggested by the disappearance of the stimulated emission band in transient absorption spectra. A theoretical calculation on the excited states identifies intermolecular electron transfer from TPE derivatives to Pd, especially for electron–rich TPE derivative. The mechanism can be general for the design of novel AIE active chemosensors.
Triple‐marker immunohistochemical assessment of muscle‐invasive bladder cancer: Is there prognostic significance?
Authors: Labban Muhieddine , Najdi Jad , Mukherji Deborah , Abou‐Kheir Wassim , Tabbarah Abeer , El‐Hajj Albert
Published: February 2021

Background

Bladder cancer is the ninth most common cancer worldwide, and the third most common cancer in Lebanon. Immunohistochemistry (IHC) has been used to stratify muscle‐invasive bladder cancer (MIBC) into different subtypes. However, to our knowledge, there exists no study that investigates the use of this low‐cost technique to predict prognosis in bladder cancer patients in our region.

Aim

To examine the feasibility of low‐cost triple‐marker IHC assessment for MIBC subtyping in order to predict patients' survival and cisplatin sensitivity.

Methods and results

We collected the specimens of deceased patients diagnosed with MIBC on pathology at our institution. For each case, tumor tissue blocks were retrieved and stained for hematoxylin and eosin in addition to three molecular markers by IHC: cytokeratin 5/6, cytokeratin 14 staining basal BC, and GATA3 staining luminal BC. A cut‐off of ≥20% was set as positive. Kaplan‐Meier curves were built, factored by BC subtype, to predict overall survival (OS), disease‐specific survival (DSS), and progression‐free survival (PFS). Hazard ratios in Cox regression were also created accounting for oncological factors and BC subtype.

We categorized specimens as either luminal (GATA3 positive only) (n = 21; 56.7%) or as double‐positive (GATA3 and basal cytokeratin 5/6 or cytokeratin 14 positive) (n = 16; 43.3%). The overall median survival was similar between the two categories (27.0 ± 4.82 months). Numbers favored luminal disease for PFS (Breslow P = .032). After adjusting for covariates, luminal molecular expression predicted PFS (0.28; [0.09‐0.94]). Yet, the Cox model was not able to identify any predictors of OS or DSS.

Conclusion

Specimens enriched with only a luminal molecular profile were more likely to exhibit cisplatin sensitivity. Despite the absence of guidelines recommending the utilization of molecular profiling in clinic practice, triple‐marker IHC could serve as a potential low‐cost prognostic indicator to identify patients at high risk of progression.
Sport action recognition by fusing multi‐source sensor information
Authors: Shi Jizu
Published: February 2021

In traditional sport and training, the quality of training plan mainly relies on individual observation and experience of coaches, which inevitably depends on individual objective opinion. With the emerging of sensors and body area network (BAN), it becomes possible to automatically recognize athletes' posture. Thus, the coaches can make decision based on recognition results to enhance athletes' competitive ability, which can greatly improve the effectiveness and quality of the sport training. This paper proposes an automatically action recognition system for sport training. First, we collect body information from body sensors. Second, the information from multi‐source sensors is input into a Kalman filter to remove the interference noise. Third, the denoised signals are divided as several unit actions according to four limbs. Fourth, the unit actions are represented as a matrix consisting of acceleration, angular velocity, combined acceleration, and combined angular velocity. We extract frequency domain features and time domain features to represent the matrix. Lastly, the extracted features are used to train an intelligent classifier which is used to predict the future postures. The experimental results on a sport training dataset demonstrates the effectiveness of our framework for action recognition for sport training.
Trajectories of depression in psychotherapy: How client characteristics predict clinical improvement
Authors: Lin Tao , Farber Barry A.
Published: February 2021

Objective

The current study aims to ascertain the trajectories of psychotherapy clients’ symptom change and identify client factors that predict treatment outcome.

Method

We conducted a latent growth mixture model (LGMM) to identify the change trajectories of 44 clients’ depression scores during psychotherapy. Client characteristics were then explored to determine whether any were associated with change trajectories. We examined whether the number of physician visits and/or client self‐concealment scores predict 63 clients’ improvement after controlling for initial symptom severity.

Results

Two trajectories of clients’ symptom change were identified: nonimprovers (52.3%) and improvers (47.7%). Nonimprovers had higher levels of self‐concealment and baseline depression than improvers. The number of physician visits was associated with higher depression scores at baseline and greater clinical improvement during psychotherapy.

Conclusion

Clients showed distinct trajectories of symptom change in psychotherapy. Early identification of clients at risk for treatment failure may increase the probability of therapeutic success.
The exponential behavior of 3D stochastic primitive equations driven by fractional noise
Authors: Wang Lidan , Zhou Guoli , Guo Boling
Published: February 2021

The long‐time behavior of flows is a very interesting and important problem in the theory of stochastic hydrodynamic equations. Inspired by the theory of dynamic system, we develop a new method to the study of the pathwise exponential behavior of 3D stochastic primitive equations driven by fractional Brownian motion. That is, we show that the weak solutions to the 3D stochastic primitive equations converge exponentially to the unique stationary solution. The result and method presented in this article can be widely applied to the study of long‐time behavior of other hydrodynamic equations with noises including Brownian motion and Lévy noise.
DVHnet: A deep learning‐based prediction of patient‐specific dose volume histograms for radiotherapy planning
Authors: Chen Xinyuan , Men Kuo , Zhu Ji , Yang Bining , Li Minghui , Liu Zhiqiang , Yan Xuena , Yi Junlin , Dai Jianrong
Published: February 2021

Purpose

To develop a deep learning method to predict patient‐specific dose volume histograms (DVHs) for radiotherapy planning.

Methods

Patient data included 180 cases with nasopharyngeal cancer, of which 153 cases were used for training and 27 for testing. A network (named “DVHnet”) based on a convolutional neural network (CNN) was designed for directly predicting DVHs of organs at risk (OARs). Two‐channel images with contoured structures were generated as the inputs for training the model. A one‐dimensional array consisting of 256 continuous volume percentages on a DVH curve for each slice was calculated as the corresponding output. The combined DVH was then calculated. Sixteen OARs were modeled in the study. Prediction accuracy was evaluated against the corresponding DVH curve of ground truth (GT) plans. A global DVH analysis and critical dosimetry metrics for each OAR were calculated for quantitative evaluation. The performance of DVHnet also was evaluated against two baselines: DosemapNet (developed by our research group) and commercial RapidPlan software.

Results

The predicted mean difference in average dose of all OARs using DVHnet was 0.30 ± 0.95 Gy. And the predicted differences in D2% and D50 can be control within 2.32 and 0.69 Gy. For most OARs, there were no obvious differences between the dosimetric metrics of the predicted and GT values for both DVHnet and DosemapNet (P ≥ 0.05). Only the predicted D2% of the optic organs for DVHnet, and of brain stem PRV for DosemapNet displayed statistically significant differences. Except for the optic organs, DVHnet performs better than or comparably with RapidPlan. The mean difference in proportion of points of interest was 3.59% ± 7.78%.

Conclusions

A deep learning network model was developed to automatically extract useful features for accurate prediction of patient‐specific DVH curves directly. The performance of DVHnet was comparable to DosemapNet and RapidPlan.
Iron(III)‐tCDTA derivatives as MRI contrast agents: Increased T1 relaxivities at higher magnetic field strength and pH sensing
Authors: Xie Jing , Haeckel Akvile , Hauptmann Ralf , Ray Iweta Pryjomska , Limberg Christian , Kulak Nora , Hamm Bernd , Schellenberger Eyk
Published: February 2021

Purpose

Low molecular weight iron(III) complex‐based contrast agents (IBCA) including iron(III) trans‐cyclohexane diamine tetraacetic acid [Fe(tCDTA)]− could serve as alternatives to gadolinium‐based contrast agents in MRI. In search for IBCA with enhanced properties, we synthesized derivatives of [Fe(tCDTA)]− and compared their contrast effects.

Methods

Trans‐cyclohexane diamine tetraacetic acid (tCDTA) was chemically modified in 2 steps: first the monoanhydride of Trans‐cyclohexane diamine tetraacetic acid was generated, and then it was coupled to amines in the second step. After purification, the chelators were analyzed by high‐performance liquid chromatography, mass spectrometry, and NMR spectrometry. The chelators were complexed with iron(III), and the relaxivities of the complexes were measured at 0.94, 1.5, 3, and 7 Tesla. Kinetic stabilities of the complexes were analyzed spectrophotometrically and the redox properties by cyclic voltammetry.

Results

Using ethylenediamine (en) and trans‐1,4‐diaminocyclohexane, we generated monomers and dimers of tCDTA: en‐tCDTA, en‐tCDTA‐dimer, trans‐1,4‐diaminocyclohexane‐tCDTA, and trans‐1,4‐diaminocyclohexane‐tCDTA‐dimer. The iron(III) complexes of these derivatives had similarly high stabilities as [Fe(tCDTA)]−. The iron(III) complexes of the trans‐1,4‐diaminocyclohexane derivatives had higher T1 relaxivities than [Fe(tCDTA)]− that increased with increasing magnetic field strengths and were highest at 6.8 L·mmol−1·s−1 per molecule for the dimer. Remarkably, the relaxivity of [Fe(en‐tCDTA)]+ had a threefold increase from neutral pH toward pH6.

Conclusion

Four iron(III) complexes with similar stability in comparison to [Fe(tCDTA)]− were synthesized. The relaxivities of trans‐1,4‐diaminocyclohexane‐tCDTA and trans‐1,4‐diaminocyclohexane‐tCDTA‐dimer complexes were in the same range as gadolinium‐based contrast agents at 3 Tesla. The [Fe(en‐tCDTA)]+ complex is a pH sensor at weakly acidic pH levels, which are typical for various cancer types.
Pharmaceutical co‐crystal: An alternative strategy for enhanced physicochemical properties and drug synergy
Authors: Ngilirabanga Jean Baptiste , Samsodien Halima
Published: February 2021

A growing number of co‐crystals in the literature are proof of how significant the co‐crystallization concept has become. Co‐crystallization enhances physicochemical properties through the formation of intermolecular interactions between a drug and a co‐former. A co‐crystal is a single crystalline material consisting of at least two molecular components solid at room temperature and present in a definite stoichiometric ratio. Pharmaceutical co‐crystals consist of the active pharmaceutical ingredient and the co‐former selected from generally regarded as safe (GRAS) list of the United State Food and Drug Administration. Co‐crystal formation requires an understanding of a drug target, a proper choice of a co‐former and is only achieved experimentally after several trials. Other beneficial co‐crystallization outcomes include binary eutectics, solid dispersions, amorphous forms, etc. Several key issues including design strategies, co‐former selection, and co‐crystallization methods; tradition and newly synthetic methods that are more efficient and suitable for large scale have been briefly described. The co‐crystal preference is demonstrated with a particular emphasis on multidrug co‐crystals and their contribution to the drug combination strategies used for the treatment and management of drug resistance and adverse side effects in serious medical conditions that require the administration of high doses such as HIV/AIDS, tuberculosis, and others.
Seaweed‐derived polymer‐based blue‐emitting C‐dots: synthesis, characterization and evaluation for iron sensing
Authors: Kholiya Faisal , Jauhari Smita , Meena Ramavatar
Published: February 2021

In recent times green and economical processes as well as sources have been in demand for the synthesis of carbon dots (C‐dots). This study demonstrates the smart utilization of seaweed‐derived polysaccharide as a green precursor for the synthesis of blue‐emitting fluorescent C‐dots using a simple, eco‐friendly and green method in an aqueous medium. The C‐dots prepared in this study were characterized using various techniques. The results confirmed that the prepared C‐dots have a cluster size of 100 nm with particle sizes in the range 5–10 nm. Prepared C‐dots emit blue photoluminescence with a good quantum yield ofca12%. Additionally, strong fluorescence quenching of C‐dots is observed in aqueous solution containing iron ions, and a selective decrease in fluorescence intensity makes it possible to determine iron in water samples in the range 0.025 to 30 ppm. Results of this work encourage us that abundantly available seaweed‐derived polysaccharides with no other commercial value could be used as green sources for the sustainable production of fluorescent, water‐soluble and biocompatible nanocarbon for selective iron sensing in aqueous solutions. © 2021 Society of Chemical Industry
Beyond history and “on a roll”: The list of the most well‐studied human protein structures and overall trends in the protein data bank
Authors: Li Zhen‐lu , Buck Matthias
Published: February 2021

Of the roughly 20,000 canonical human protein sequences, as of January 20, 2021, 7,077 proteins have had their full or partial, medium‐ to high‐resolution structures determined by x‐ray crystallography or other methods. Which of these proteins dominate the protein data bank (the PDB) and why? In this paper, we list the 273 top human protein structures based on the number of their PDB entries. This set of proteins accounts for more than 40% of all available human PDB entries and represent past trends as well as current status for protein structural biology. We briefly discuss the relationship which some of the prominent protein structures have with protein research as a whole and mention their relevance to human diseases. The top‐10 soluble and membrane proteins are all well‐known (most of their first structures being deposited more than 30 years ago). Overall, there is no dramatic change in recent trends in the PDB. Remarkably, the number of structure depositions has grown nearly exponentially over the last 10 or more years (with a doubling time of 7 years for proteins, obtained from any organism). Growth in human protein structures is slightly faster (at 5.9 years). The information in this paper may be informative to senior scientists but also inspire researchers who are new to protein science, providing the year 2021 snap‐shot for the state of protein structural biology.
A detailed mapping of the readily accessible disulphide bonds in the cortex of wool fibres
Authors: Plowman Jeffrey E. , Miller Rachel E. , Thomas Ancy , Grosvenor Anita J. , Harland Duane P. , Deb‐Choudhury Santanu
Published: February 2021

Trichocyte keratin intermediate filament proteins (keratins) and keratin associated proteins (KAPs) differ from their epithelial equivalents by having significantly more cysteine residues. Interactions between these cysteine residues within a mammalian fiber, and the putative regular organization of interactions are likely important for defining fiber mechanical properties, and thus biological functionality of hairs. Here we extend a previous study of cysteine accessibility under different levels of exposure to reducing compounds to detect a greater resolution of statistically non‐random interactions between individual residues from keratins and KAPs. We found that most of the cysteines with this non‐random accessibility in the KAPs were close to either the N‐ or C‐ terminal domains of these proteins. The most accessible non‐random cysteines in keratins were present in the head or tail domains, indicating the likely function of cysteine residues in these regions is in readily forming intermolecular bonds with KAPs. Some of the less accessible non‐random cysteines in keratins were discovered either close to or within the rod region in positions previously identified in human epithelial keratins as involved in crosslinking between the heterodimers of the tetramer. Our present study therefore provides a deeper understanding of the accessibility of disulfides in both keratins and KAPs and thus proves that there is some specificity to the disulfide bond interactions leading to these inter‐ and intra‐molecular bonds stabilizing the fiber structure. Furthermore, these suggest potential sites of interaction between keratins and KAPs as well as keratin‐keratin interactions in the trichocyte intermediate filament.
Protein dynamics analysis identifies candidate cancer driver genes and mutations inTCGAdata
Authors: Sayılgan Jan Fehmi , Haliloğlu Türkan , Gönen Mehmet
Published: February 2021

Recently, it has been showed that cancer missense mutations selectively target the neighborhood of hinge residues, which are key sites in protein dynamics. Here, we show that this approach can be extended to find previously unknown candidate mutations and genes. To this aim, we developed a computational pipeline to detect significantly enriched three‐dimensional (3D) clustering of missense mutations around hinge residues. The hinge residues were detected by applying a Gaussian network model. By systematically analyzing the PanCancer compendium of somatic mutations in nearly 10 000 tumors from the Cancer Genome Atlas, we identified candidate genes and mutations in addition to well known ones. For instance, we found significantly enriched 3D clustering of missense mutations in known cancer genes including CDK4, CDKN2A, TCL1A, and MAPK1. Beside these known genes, we also identified significantly enriched 3D clustering of missense mutations around hinge residues in PLA2G4A, which may lead to excessive phosphorylation of the extracellular signal‐regulated kinases. Furthermore, we demonstrated that hinge‐based features improves pathogenicity prediction for missense mutations. Our results show that the consideration of clustering around hinge residues can help us explain the functional role of the mutations in known cancer genes and identify candidate genes.
Oxidation shuts down an auto‐inhibitory mechanism of von Willebrand factor
Authors: Tsai Rachel , Interlandi Gianluca
Published: February 2021

The blood protein von Willebrand factor (VWF) is a key link between inflammation and pathological thrombus formation. In particular, oxidation of methionine residues in specific domains of VWF due to the release of oxidants in inflammatory conditions has been linked to an increased platelet‐binding activity. However, the atomistic details of how methionine oxidation activates VWF have not been elucidated to date. Yet understanding the activation mechanism of VWF under oxidizing conditions can lead to the development of novel therapeutics that target VWF selectively under inflammatory conditions in order to reduce its thrombotic activity while maintaining its haemostatic function. In this manuscript, we used a combination of a dynamic flow assay and molecular dynamics (MD) simulations to investigate how methionine oxidation removes an auto‐inhibitory mechanism of VWF. Results from the dynamic flow assay revealed that oxidation does not directly activate the A1 domain, which is the domain in VWF that contains the binding site to the platelet surface receptor glycoprotein Ibα (GpIbα), but rather removes the inhibitory function of the neighboring A2 and A3 domains. Furthermore, the MD simulations combined with free energy perturbation calculations suggested that methionine oxidation may destabilize the binding interface between the A1 and A2 domains leading to unmasking of the GpIbα‐binding site in the A1 domain.
A survey of human histone H1 subtypes interaction networks: Implications for histones H1 functioning
Authors: Kowalski Andrzej
Published: February 2021

To show a spectrum of histone H1 subtypes (H1.1‐H1.5) activity realized through the protein‐protein interactions, data selected from APID resources were processed with sequence‐based bioinformatics approaches. Histone H1 subtypes participate in over half a thousand interactions with nuclear and cytosolic proteins (ComPPI database) engaged in the enzymatic activity and binding of nucleic acids and proteins (SIFTER tool). Small‐scale networks of H1 subtypes (STRING network) have similar topological parameters (P > .05) which are, however, different for networks hubs between subtype H1.1 and H1.4 and subtype H1.3 and H1.5 (P < .05) (Cytoscape software). Based on enriched GO terms (g:Profiler toolset) of interacting proteins, molecular function and biological process of networks hubs is related to RNA binding and ribosome biogenesis (subtype H1.1 and H1.4), cell cycle and cell division (subtype H1.3 and H1.5) and protein ubiquitination and degradation (subtype H1.2). The residue propensity (BIPSPI predictor) and secondary structures of interacting surfaces (GOR algorithm) as well as a value of equilibrium dissociation constant (ISLAND predictor) indicate that a type of H1 subtypes interactions is transient in term of the stability and medium‐strong in relation to the strength of binding. Histone H1 subtypes bind interacting partners in the intrinsic disorder‐dependent mode (FoldIndex, PrDOS predictor), according to the coupled folding and binding and mutual synergistic folding mechanism. These results evidence that multifunctional H1 subtypes operate via protein interactions in the networks of crucial cellular processes and, therefore, confirm a new histone H1 paradigm relating to its functioning in the protein‐protein interaction networks.
Policy for innovative entrepreneurship: Institutions, interventions, and societal challenges
Authors: Bradley Steven W. , Kim Phillip H. , Klein Peter G. , McMullen Jeffery S. , Wennberg Karl
Published: February 2021

Research Summary

Innovative entrepreneurship, defined as the creation of new products, services, production methods, or business models, is critical for firm, industry, and economic growth and a key determinant of societal well‐being. This special issue explores the roles of institutions and government policies in promoting or impeding innovative entrepreneurship. In this introductory editorial, we review theory and evidence on entrepreneurship at the macro‐institutional and micro‐policy levels, highlighting costs and benefits of alternative institutional environments and targeted policy interventions, as well as interactions within and across levels. We summarize the six papers in the special issue, discuss their contributions to the literature, and suggest how future work can build upon these and other papers to advance our understanding of the conditions and mechanisms underlying successful entrepreneurial innovation.

Managerial Summary

Innovation and entrepreneurship bring new products and services to market, help firms and industries to grow, and generate improvements in social and economic life. The papers in this special issue explore the background conditions—laws, political processes, regulations, tax policy, subsidies, training programs, and more—that make entrepreneurship and innovation successful. Both “macro” and “micro” policies can stimulate successful entrepreneurial and innovative outcomes, but can also become politicized, be ineffective, and generate unintended consequences. The papers offer lessons to researchers, policymakers, and practitioners about making entrepreneurship and innovation more successful.
The Science of Science
Authors: Wang Dashun , Barabási Albert-László
Published: February 2021

This is the first comprehensive overview of the 'science of science,' an emerging interdisciplinary field that relies on big data to unveil the reproducible patterns that govern individual scientific careers and the workings of science. It explores the roots of scientific impact, the role of productivity and creativity, when and what kind of collaborations are effective, the impact of failure and success in a scientific career, and what metrics can tell us about the fundamental workings of science. The book relies on data to draw actionable insights, which can be applied by individuals to further their career or decision makers to enhance the role of science in society. With anecdotes and detailed, easy-to-follow explanations of the research, this book is accessible to all scientists and graduate students, policymakers, and administrators with an interest in the wider scientific enterprise.
Forecasting the Frequency and Magnitude of Postfire Debris Flows Across Southern California
Authors: Kean Jason W. , Staley Dennis M.
Published: February 2021

Southern California has a long history of damaging debris flows after wildfire. Despite recurrent loss, forecasts of the frequency and magnitude of postfire debris flows are not available for the region like they are for earthquakes. Instead, debris flow hazards are typically assessed in a reactive manner after wildfires. Such assessments are crucial for evaluating debris flow risk by postfire emergency response teams; however, time between the fire and first rainstorm is often insufficient to fully develop and implement effective emergency response plans like those in place for earthquakes. Here, we use both historical distributions of fire and precipitation frequency and empirical models of postfire debris flow likelihood and volume to map the expected frequency and magnitude of postfire debris flows across southern California. We find that at least small debris flows can be expected almost every year, while major debris flows capable of damaging 40 or more structures have a recurrence interval between 10 and 13 years, a return interval that is comparable to a magnitude 6.7 earthquake. A sensitivity analysis to possible future changes in current fire and precipitation regimes indicates that debris flow activity in southern California is more sensitive to increases in precipitation intensity than increases in fire frequency and severity. Projected increases in rainfall intensity of 18% result in an overall 110% increase in the probability of major debris flows. Our results, in combination with an assessment of exposure, can be used to prioritize watersheds for further analysis and possible prefire mitigation.
Ensemble Kalman Filter Parameter Estimation of Ocean Optical Properties for Reduced Biases in a Coupled General Circulation Model
Authors: Kitsios V. , Sandery P. , O’Kane T. J. , Fiedler R.
Published: February 2021

Coupled general circulation models (GCM), and their atmospheric, oceanic, land, and sea‐ice components have many parameters. Some parameters determine the numerics of the dynamical core, while others are based on our current understanding of the physical processes being simulated. Many of these parameters are poorly known, often globally defined, and are subject to pragmatic choices arising from a complex interplay between grid resolution and inherent model biases. To address this problem, we use an ensemble transform Kalman filter, to estimate spatiotemporally varying maps of ocean albedo and shortwave radiation e‐folding length scale in a coupled climate GCM. These parameters are designed to minimize the error between short term (3–28 days) forecasts of the climate model and a network of real world atmospheric, oceanic, and sea‐ice observations. The data assimilation system has an improved fit to observations when estimating ocean albedo and shortwave e‐folding length scale either individually or simultaneously. However, only individually estimated maps of shortwave e‐folding length scale are also shown to systematically reduce bias in longer multiyear climate forecasts during an out‐of‐sample period. The bias of the multiyear forecasts is reduced for parameter maps determined from longer DA cycle lengths.
Understanding Ground Rupture Due to Groundwater Overpumping by a Large Lab Experiment and Advanced Numerical Modeling
Authors: Nardean S. , Ferronato M. , Zhang Y. , Ye S. , Gong X. , Teatini P.
Published: February 2021

Ground rupture due to groundwater pumping is a major environmental hazard accompanying land subsidence in some areas. Ground ruptures usually develop when a significant compaction affects a sedimentary sequence with peculiar geological conditions, for example, the presence of a shallow bedrock with buried ridges. A laboratory test was developed with the aim at improving our understanding of the mechanisms responsible for rupture generation in this particular hydrogeological setting, typical, for instance, of the Guangming village, China. A 0.8‐m high concrete prism, representing a rocky ridge, was placed in a 4.0‐m long, 1.8‐m wide, and 1.4‐m high box and buried by alluvial material. The box was saturated and then drained, with the formation of a main crack above the prism‐shaped ridge. The measured water content, vertical displacements, strains, rupture initiation, and growth are analyzed through an original coupled 3D‐numerical model, simulating the variably saturated groundwater flow in a deformable and fractured porous medium. To our knowledge, this is the first application of such a kind of model to a lab‐scale experiment. Despite the uncertainty on the material parameters, the numerical model allows satisfactorily reproducing the observed groundwater flow, land subsidence, and rupture features (depth and width). The rupture dynamics is captured in part as well, despite the employment of a simple Mohr–Coulomb failure criterion and although other forces (e.g., electrochemical) may likely play a role at the metric scale of the lab test. The modeling outcomes provide a clear view on how the rupture develops from the surface and propagates downward.
Installation Matters: Implications for In Situ Water Quality Monitoring
Authors: Erwin Elizabeth G. , McLaughlin Daniel L. , Stewart Ryan D.
Published: February 2021

Novel in situ sensor technologies can measure water chemistry at high temporal frequencies, yet few studies have evaluated how installation affects measurements. In this study, we assessed the effects of commonly used protective housings on in situ sensor readings. Working in two mountain streams, we colocated specific conductance sensors in four different housing types that varied in openings for water exchange (mesh, screen, holes, and open). We compared measured conductance values through time and performed repeated salt tracer additions to evaluate the influence of housing type on calculated discharge. Sensors readings in mesh and, to a lesser extent, screen housings frequently diverged from housings with larger openings (i.e., holes and open), indicating reduced water exchange between stream water and housed sensors. Further, mesh and screen housings recorded more damped and delayed response to salt tracer additions compared to the other two housings, resulting in markedly different discharge values. From these findings, we recommend that water chemistry sensors should be deployed in a protective housing with large openings for sufficient water exchange.
Incorporating the Memory Effect of Turbulence Structures Into Suspended Sediment Transport Modeling
Authors: Tsai Christina W. , Huang Shih‐Hsun , Hung Serena Y.
Published: February 2021

Modeling of the random movement of fine sediment particles in open‐channel turbulent flow is mostly built upon the memoryless Brownian motion process. Such a process describes the chaotic behavior of small particles without considering temporal correlations in terms of the particle moving velocity and direction (i.e., memory). However, when particles are transported in time‐persistent turbulent flow, the movements of the suspended particles may exhibit persistency that depends on the various temporal durations of turbulent flow structures—such persistence results in direction and magnitude variations in the velocity of the fine moving particles. The diffusion property of the particles may then deviate from normal diffusion. The conventional memoryless random walk models may not provide a comprehensive description of the particle diffusion process for the duration of turbulence structures when the particles are subject to memory effects. In this study, a novel random walk model is proposed to present the temporal correlation of the suspended sediment particle velocity caused by turbulence structures in open channel flow. The probabilistic properties of the proposed model are discussed. In particular, enhanced physical insights are obtained regarding the particle diffusion behavior in turbulent flows. Numerical simulations are conducted to demonstrate that, similar to the conventional memoryless random walk models, the proposed model shows normal diffusion for long‐term observations, despite its local superdiffusion behavior. The effective diffusion coefficient of the proposed stochastic process on a long‐term time scale is formulated.
Predicting Latent and Sensible Heat Fluxes in Stream Temperature Models: Current Challenges and Potential Solutions
Authors: Moore R. D. , Leach J. A.
Published: February 2021

Stream temperature studies typically use either the Penman combination equation (PCE) or empirical wind functions to compute the latent heat flux, which can be an important control on daily maximum water temperature. The sensible heat flux is usually computed from the latent heat flux via the Bowen ratio or a bulk transfer model. Unfortunately, both the PCE and empirical wind functions involve challenges. The PCE is inappropriate for application to subdaily stream evaporation because, as implemented in many stream temperature studies, it does not account for energy associated with warming or cooling of the water column or bed heat fluxes. The PCE thus tends to overestimate evaporation under conditions typical of warm summer days during the diurnal warming phase, which is when evaporation is likely to be an important heat loss mechanism. Empirical wind functions involve substantial uncertainty given the broad range of coefficient values that have been reported in the literature and the lack of above‐stream meteorological data to use in their application. We provide suggestions for improving current practice and also identify research directions to support development of robust approaches to computing the latent and sensible heat fluxes.
Catalytic asymmetric transformations of oxa- and azabicyclic alkenes
Authors: Vivek Kumar Sundaravel , Yen Andy , Lautens Mark , Guiry Patrick J.
Published: February 2021

This review provides an overview of the fundamental concepts and recent developments in a wide range of enantioselective transformations involving oxa- and azabicyclic alkenes.
New glycine derived peptides bearing benzenesulphonamide as an antiplasmodial agent
Authors: Ugwuja Daniel Izuchukwu , Okoro Uchechukwu , Soman Shubhanji , Ibezim Akachukwu , Ugwu David , Soni Rina , Obi Bonaventure , Ezugwu James , Ekoh Ogechi
Published: February 2021

In the tropics, malaria is among the most serious infectious diseases in developing countries. The discovery of the artemesinin antimalarial drug not too long ago was a major breakthrough in the effort to combat the malaria disease.
A homologous-targeting “nanoconverter” with variable size for deep tumor penetration and immunotherapy
Authors: Cong Cong , Jiaxin Bian , Liu Xiaokang , Zhang Xinyue , Fu Yihan , Li Zhuo , Xu Zichuang , Wei Shipan , Wang Desong , Gao Dawei
Published: February 2021

Schematic of the fabrication of PTX/PDA@M-C6 for deep penetration, photothermal response release, specific tumor apoptosis and immunotherapy.
New advances on Au–magnetic organic hybrid core–shells in MRI, CT imaging, and drug delivery
Authors: Mohajer Fatemeh , Mohammadi Ziarani Ghodsi , Badiei Alireza
Published: February 2021

Magnetic nanoparticles have been studied for scientific and technological applications such as magnetic storage media, contrast agents for magnetic resonance imaging, biolabelling, separation of biomolecules, and magnetic-targeted drug delivery.
Compound Cocktail Inhibits Influenza Viral Pneumonia via Phospholipase Cγ1 Phosphorylation-Related Necroptosis and Partial Autophagy in Natural Killer Cells
Authors: Ma Rong , Ma Rui-Qing , Chen Bei , Wang Li-Yu , Fan Xiao-Yong
Published: February 2021

Influenza viral infections are prone to global outbreaks and cause pneumonia in affected populations. High morbidity and mortality caused by pneumonia occur during an influenza pandemic. Antivirals or control of inflammation is the primary means of influenza treatment. A compound cocktail composed of arctiin, daidzein, glycyrrhizic acid, and liquiritin inhibited mouse pneumonia resulting from a PR8 viral infection and caused a weight gain after oral administration. Natural killer cell activating receptors, both Ly49D and Ly49H in the lungs, were increased in the treatment in mice. In H3N2 virus-infected natural killer-92MI cells, the cocktail treatment had different effects on phosphorylation sites of phospholipase Cγ1 (PLCγ1) and killed infected cells through necroptosis or late apoptosis, in which RIP3 was increased and both caspase-3 and phosphorylated-JNK in the cells were downregulated. Acid phosphatase activity in viral-infected natural killer-92MI cells was induced by the compound cocktail treatment, which could be related to the p62 decrease in natural killer-92MI cells. In addition, an autophagic flux induction was observed in alveolar basal epithelial cells (A549). Protein p65, but not phosphorylated-p65, was significantly decreased by the treatment. Our results indicate that the compound cocktail strengthened the phosphorylation of PLCγ1-related necroptosis and partial autophagy in natural killer cells, which could yield an inhibitory effect on viral pneumonia in influenza.
Bioaccessibility and Absorption of Flavonoid C-glycosides from Abrus mollis Using Simulated Digestion, Caco-2 Cell, and In Situ Single-pass Perfusion Models
Authors: Shen Wei , Hu Xiaolong , Niu Yajun , Lu Yimeng , Wang Baolin , Wang Hao
Published: February 2021

Abrus mollis is commonly used as a traditional Chinese medicine for the treatment of liver diseases due to its hepatoprotection and anti-inflammation, but the absorption properties of its main bioactive ingredients remain unclear. Our previous studies verified that the flavonoid C-glycosides, including vicenin-2 (1), isoschaftoside (2), and schaftoside (3), were the major active components in A. mollis for hepatic protection against nonalcoholic fatty liver disease, hepatitis, and hepatic fibrosis. This study investigated the bioaccessibility and transport mechanisms of total flavonoid C-glycoside, as well as vicenin-2 (1), isoschaftoside (2), and schaftoside (3), in A. mollis by simulated digestion and use of the Caco-2 cell model. Moreover, this study attempted to verify their absorption properties by in situ gastrointestinal perfusion in rats. Total flavonoid C-glycoside and 1, 2, and 3 exhibited similar bioaccessibility of 84.58%, 85.13%, 83.05%, and 81.65% respectively after simulated digestion. The transport of total flavonoid C-glycoside in the Caco-2 cell model increased with the concentration, and the transport showed saturation characteristics with the time and concentration of total flavonoid C-glycoside to a certain degree. The Papp values of total flavonoid C-glycoside and the 3 flavonoid C-glycosides were significantly improved by verapamil, probenecid, and EDTA-Na2. Their absorption properties in the gastrointestinal tract were consistent with that found in Caco-2 cells, and superior absorption rates were observed in the duodenum and jejunum. The absorption pattern of total flavonoid C-glycoside may involve multiple transport pathways, including active transport, passive diffusion, and the paracellular pathway. TFC was actively pumped out by P-glycoprotein and multidrug
resistance-associated protein. These results revealed that the bioaccessibility and intestinal absorption characteristic of total flavonoid C-glycoside were consistent with the 3 major flavonoids.
DMAP-Catalyzed Reaction of Diethyl 1,3-Acetonedicarboxylate with 2-Hydroxybenzylideneindenediones: Facile Synthesis of Fluorenone-Fused Coumarins
Authors: Shkoor Mohanad , Bayari Raghad
Published: February 2021

The base-catalyzed reaction of diethyl 1,3-acetonedicarboxylate with 2-hydroxybenzylidene indenediones was studied. The reaction provides a facile and expeditious protocol for the synthesis of natural product inspired fluorenone-fused coumarins in good to very good yields. This process resembles a combination of domino Michael–intramolecular Knoevenagel–aromatization–lactonization reactions in a single step. Although this reaction operates with many bases, the best yields were obtained with DMAP as a catalyst. This protocol could open new potential avenues for the synthesis of fused coumarins by the reaction of substituted β-keto esters with different 2-(2-hydroxybenzylidenes) of 1,3-dicarbonyl compounds.
(3+2)-Cycloaddition of Donor–Acceptor Cyclopropanes with Thiocyanate: A Facile and Efficient Synthesis of 2-Amino-4,5-dihydrothiophenes
Authors: Werz Daniel B. , Jacob Anu , Barkawitz Philip , Andreev Ivan A. , Ratmanova Nina K. , Trushkov Igor V.
Published: February 2021

An easy and efficient route to obtain 2-amino-4,5-dihydrothiophenes is presented. A formal (3+2)-cycloaddition of donor–acceptor cyclopropanes and ammonium thiocyanate catalyzed by Yb(OTf)3 delivers the desired products in good to excellent yields. A broad range of functional groups is tolerated during this process.
Outcomes of Combined Unicondylar Knee Arthroplasty and Anterior Cruciate Ligament Reconstruction
Authors: Aslan Hakan , Çevik Hüseyin Bilgehan
Published: February 2021

Young and more active patients with medial compartmental osteoarthritis (OA) in conjunction with anterior cruciate ligament (ACL) deficiency are challenging for orthopaedic surgeons. The aim of the present study was to examine the early–mid clinical and radiological outcomes of combined Oxford unicondylar knee arthroplasty (UKA) and ACL reconstruction for the patients presenting ACL deficiency and concomitant medial compartment symptomatic OA. Twelve patients were included in the study. All patients were treated by combination of ACL reconstruction with medial UKA. The varus–valgus angles of the tibial and femoral components, and pathological radiolucent lines were measured on anteroposterior and lateral knee radiographs. Clinical evaluations include knee osteoarthritis outcome score (KOOS pain, symptom, daily life, sports, and quality of life), Oxford knee score (OKS), EQ-5D-3L, and EQ-visual analog scale (VAS). All the patients were followed up for an average of 45.6 months. The leg alignment showed 3.6 degrees ± 1 of varus deformity before surgery and 2.6 degrees ± 1 of valgus after surgery. With the exception of KOOS sports (p > 0.001), the KOOS pain, symptom, daily life, and quality of life, OKS, EQ-5D-3L, and EQ-VAS improved significantly after surgery (p < 0.001). Preoperative knee instability showed anterior translation of 5 to 10 mm in eight patients and >10 mm in four patients. There were no complications at follow-up. The early–mid clinical data have shown that UKA in conjunction with ACL reconstruction has revealed promising results. However, long-term follow-up studies are required to confirm the combined procedure in these patients.
Impact of Biological Sex on Complications, Lengths of Stay, Readmission Rates, and Costs of Care Following Primary Total Knee Arthroplasty
Authors: Swiggett Samuel J. , Mannino Angelo , Vakharia Rushabh M. , Ehiorobo Joseph O. , Roche Martin W. , Mont Michael A. , Erez Orry
Published: February 2021

The impact of gender on total knee arthroplasty (TKA) postoperative complications, readmission rates, and costs of care has not been often evaluated. Therefore, the purpose of this study was to investigate which sex had higher rates of: (1) medical complications; (2) implant complications; (3) lengths of stay (LOSs); (4) readmission rates; and (5) costs after TKA. A query was performed using an administrative claims database from January 1, 2005, to March 31, 2015. Patients who had TKAs were identified using International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Males and females were filtered separately and matched according to age and various medical comorbidities leading to 1,590,626 patients equally distributed. Primary outcomes analyzed included 90-day medical complications, LOSs, 90-day readmission rates, in addition to day of surgery and total global 90-day episode of care costs. Pearson's chi-square analyses were used to compare medical complications and readmission rates. Welch's t-tests were used to test for significance in matching outcomes and costs. A p-value of less than 0.01 was considered statistically significant. Males had a smaller risk of complications than women (1.35 vs. 1.40%, p < 0.006) and higher rates of implant-related complications (2.28 vs. 1.99%, p < 0.0001). Mean LOSs were lower for males: 3.16 versus 3.34 days (p < 0.0001). The 90-day readmission rates were higher in men (9.67 vs. 8.12%, p < 0.0001). This study demonstrated that males undergoing primary TKA have lower medical complications and shorter LOSs then their female counterparts. However, males have higher implant-related complications, readmission rates, and costs of care.