bluuebunny/crossref_metadata_2025 huggingface dataset:
Regiodivergent C−H and Decarboxylative C−C Alkylation by Ruthenium Catalysis: ortho versus meta Position‐Selectivity
Authors: Korvorapun Korkit , Moselage Marc , Struwe Julia , Rogge Torben , Messinis Antonis M. , Ackermann Lutz
Published: July 2020

Ruthenium(II)biscarboxylate complexes enabled the selective alkylation of C−H and C−C bonds at the ortho‐ or meta‐position. ortho‐C−H Alkylations were achieved with 4‐, 5‐ as well as 6‐membered halocycloalkanes. Furthermore, the judicious choice of the directing group allowed for a full control of ortho‐/meta‐selectivities. Detailed mechanistic studies by experiment and computation were performed and provided strong support for an oxidative addition/reductive elimination process for ortho‐alkylations, while a homolytic C−X cleavage was operative for the meta‐selective transformations.
Kinetic versus Thermodynamic Control Over Multiple Conformations of Di‐2,7‐naphthihexaphyrin(1.1.1.1.1.1)
Authors: Szyszko Bartosz , Rymut Paweł , Matviyishyn Maksym , Białońska Agata , Latos‐Grażyński Lechosław
Published: July 2020

Di‐2,7‐naphthihexaphyrin(1.1.1.1.1.1), a non‐aromatic carba‐analogue of the hexaphyrin(1.1.1.1.1.1), incorporating two built‐in 2,7‐naphthylene moieties was synthesized as two separate, conformationally locked stereoisomers. Both conformers followed complex protonation pathways involving structurally different species, which can be targeted under kinetic and thermodynamic control. The neutralization of the ultimate dicationic product, accessible from both stereoisomers of the free base, allowed to realize the complex conformational switching cycle involving six structurally different species.
Smart Nanocarriers for the Delivery of Nucleic Acid‐Based Therapeutics: A Comprehensive Review
Authors: Ramasamy Thiruganesh , Munusamy Shankar , Ruttala Hima Bindu , Kim Jong Oh
Published: July 2020

Nucleic acid‐based therapies are promising therapeutics for the treatment of several systemic disorders, and they offer an exciting opportunity to address emerging biological challenges. The scope of nucleic acid‐based therapeutics in the treatment of multiple disease states including cancers has been widened by recent progress in Ribonucleic acids (RNA) biology. However, cascades of systemic and intracellular barriers, including rapid degradation, renal clearance, and poor cellular uptake, hinder the clinical effectiveness of nucleic acid‐based therapies. These barriers can be circumvented by utilizing advanced smart nanocarriers that efficiently deliver and release the encapsulated nucleic acids into the target tissues. This review describes the current status of clinical trials on nucleic acid‐based therapeutics and highlights representative examples that provide an overview on the current and emerging trends in nucleic acid‐based therapies. A better understanding of the design of advanced nanocarriers is essential to promote the translation of therapeutic nucleic acids into a clinical reality.
Development and validation of a clinicopathological‐based nomogram to predict seeding risk after percutaneous thermal ablation of primary liver carcinoma
Authors: An Chao , Huang Zhimei , Ni Jiayan , Zuo Mengxuan , Jiang Yiquan , Zhang Tianqi , Huang Jin‐Hua
Published: July 2020

Objectives

To develop a clinicopathological‐based nomogram to improve the prediction of the seeding risk of after percutaneous thermal ablation (PTA) in primary liver carcinoma (PLC).

Methods

A total of 2030 patients with PLC who underwent PTA were included between April 2009 and December 2018. The patients were grouped into a training dataset (n = 1024) and an external validation dataset (n = 1006). Baseline characteristics were collected to identify the risk factors of seeding after PTA. The multivariate Cox proportional hazards model based on the risk factors was used to develop the nomogram, which was used for assessment for its predictive accuracy using mainly the Harrell's C‐index and receiver operating characteristic curve (AUC).

Results

The median follow‐up time was 30.3 months (range, 3.2‐115.7 months). The seeding risk was 0.89% per tumor and 1.5% per patient in the training set. The nomogram was developed based on tumor size, subcapsular, α‐fetoprotein (AFP), and international normalized ratio (INR). The 1‐, 2‐, and 3‐year cumulative seeding rates were 0.1%, 0.7% and 1.2% in the low‐risk group, and 1.7%, 6.3% and 6.3% in the high‐risk group, respectively, showing significant statistical difference (P < .001). The nomogram had good calibration and discriminatory abilities in the training set, with C‐indexes of 0.722 (95% confidence interval [CI]: 0.661, 0.883) and AUC of 0.850 (95% CI: 0.767, 0.934). External validation with 1000 bootstrapped sample sets showed a good C‐index of 0.706 (95% CI: 0.546, 0.866) and AUC of 0.736 (95% CI: 0. 646, 0.827).

Conclusions

The clinicopathological‐based nomogram could be used to quantify the probability of seeding risk after PTA in PLC.
PR10/Bet v1‐like Proteins as Novel Contributors to Plant Biochemical Diversity
Authors: Morris Jeremy S. , Caldo Kristian Mark P. , Liang Siyu , Facchini Peter J.
Published: July 2020

Pathogenesis‐related (PR) proteins constitute a broad class of plant proteins with analogues found throughout nature from bacteria to higher eukaryotes. PR proteins were first noted in plants as part of the hypersensitive response, but have since been assigned an array of biological roles. The PR10/Bet v1‐like proteins are a subset of PR proteins characterized by an ability to bind a wide range of lipophilic ligands, uniquely positioning them as contributors to specialized biosynthetic pathways. PR10/Bet v1‐like proteins participate in the production of plant alkaloids and phenolics including flavonoids, both as general binding proteins and in special cases as catalysts. Owing initially to the perceived allergenic properties of PR10/Bet v1‐like proteins, many were studied at the structural level to elucidate the basis for ligand binding. These studies provided a foundation for more recent efforts to understand higher‐level structural order and how PR10/Bet v1‐like proteins catalyse key reactions in plant pathways. Synthetic biology aimed at reconstituting plant‐specialized metabolism in microorganisms uses knowledge of these proteins to fine‐tune performance in new systems.
Endocrinopathies in Aicardi Goutières syndrome—A descriptive case series
Authors: Worth Chris , Briggs Tracy A , Padidela Raja , Balmer Eleanor , Skae Mars
Published: July 2020

Hypothyroidism and diabetes insipidus present in children with Aicardi Goutières Syndrome (AGS) often years after disease onset and frequently resolve spontaneously. Screening and regular reassessment for both conditions are recommended in all children with AGS.
Amidation of Aldehydes with Amines under Mild Conditions Using Metal‐Organic Framework Derived NiO@Ni Mott‐Schottky Catalyst
Authors: Goel Bharat , Vyas Ved , Tripathi Nancy , Kumar Singh Ajit , Menezes Prashanth W. , Indra Arindam , Jain Shreyans K.
Published: July 2020

Here we report a facile method for the synthesis of nickel oxide‐nickel (NiO@Ni) Mott‐Schottky catalyst employing metal‐organic framework (MOF) as the precursor. A direct amidation protocol of aldehydes with amines has been optimized under mild conditions using NiO@Ni Mott‐Schottky catalyst and it shows far better catalytic activity than the NiO−Ni nanoparticles prepared from simple Ni2+ salt under similar reaction conditions. The heterogeneous catalyst is robust, recyclable and efficient to provide comparable yield to costly ligand‐based homogeneous Ni catalysts. The scope of the reaction protocol has been explored with variably substituted substrates. The reaction initiates by homolytic cleavage of peroxide and proceeds through radical mechanism.
Enantioselective Synthesis of cis‐2,6‐Disubstituted‐4‐methylene Tetrahydropyrans via Chromium Catalysis†
Authors: Bai Jing , Chen Bin , Zhang Guozhu
Published: July 2020

Summary of main observation and conclusion

Enantioenriched 2,6‐disubstituted 4‐methylene tetrahydropyrans have been obtained via a two‐step sequence consisting of a highly enantioselective chromium‐catalyzed carbonyl 2‐(trimethylsilyl methyl)allylation and Prins cyclization. Commercially available (2‐(chloromethyl)allyl)trimethylsilane serves as the bifunctional linchpin to combine two aldehydes to assemble the 2,6‐disubstituted pyrans. A variety of functional groups are compatible under the mild reaction conditions. The synthetic utility of this methodology was demonstrated by the asymmetric synthesis of 16 examples of homoallylic alcohol and 8 examples of 2,6‐disubstituted 4‐methylene tetrahydropyrans, including an advanced intermediate which could be transformed to natural product centrolobine via a known procedure.
Optimizing execution for pipelined‐based distributed deep learning in a heterogeneously networked GPU cluster
Authors: Zhang Jinghui , Zhan Jun , Li Jiange , Jin Jiahui , Qian Lei
Published: July 2020

Exorbitant resources (computing and memory) are required to train a deep neural network (DNN). Often researchers deploy an approach that uses distributed parallel training to acquire larger models faster on GPUs. This approach has its detriments, though; on one hand, a GPU's expanded capacity to compute also produces bigger bottlenecks in inter‐GPU's communications during model training, and multi‐GPU systems lead to complex connectivity. Workload schedulers then end up having to consider hardware topology and requirements for workload communication, in hopes of allocating GPU resources to optimize execution time and improve usage in a heterogeneous environment. On the other hand, the high memory requirements to train a DNN model make running the training processes on GPUs onerous. To contend with this, we introduce two execution optimization methods based on pipeline‐hybrid parallelism (using both data and model parallelism) in a GPU cluster with heterogeneous networking. First, we propose a model partition algorithm that accelerates pipeline‐hybrid parallelism training between heterogeneously network‐connected GPUs. Second, we introduce a cost‐balanced recomputing algorithm to reduce memory usage in the pipeline mode. Experiments show that our solution (Pipe‐Torch) averages a speedup of 1.4× compared with data parallelism, and reduces the memory footprint while maintaining pipelined load‐balanced training.
A novel data partitioning algorithm for dynamic energy optimization on heterogeneous high‐performance computing platforms
Authors: Khaleghzadeh Hamidreza , Fahad Muhammad , Reddy Manumachu Ravi , Lastovetsky Alexey
Published: July 2020

Energy is one of the most important objectives for optimization on modern heterogeneous high‐performance computing (HPC) platforms. The tight integration of multicore CPUs with accelerators such as graphical processing units (GPUs) and Xeon Phi coprocessors in these platforms presents several challenges to the optimization of multithreaded data‐parallel applications for energy. In this work, the problem of optimization of data‐parallel applications on heterogeneous HPC platforms for dynamic energy through workload distribution is formulated. We propose a workload partitioning algorithm to solve this problem. It employs load‐imbalancing technique to determine the workload distribution minimizing the dynamic energy consumption of the parallel execution of an application. The inputs to the algorithm are discrete dynamic energy profiles of individual computing devices. The profiles are practically constructed using an approach that accurately models the energy consumption by execution of a hybrid scientific data‐parallel application on a heterogeneous platform containing different computing devices such as CPU, GPU, and Xeon Phi. The proposed algorithm is experimentally analyzed using two multithreaded data‐parallel applications, matrix multiplication and 2D fast Fourier transform. The load‐imbalanced solutions provided by the algorithm achieve significant dynamic energy reductions for the two applications (in average by 130% and 44%, respectively) compared with the load‐balanced solutions.
A deep learning model for mining and detecting causally related events in tweets
Authors: Kayesh Humayun , Islam Md. Saiful , Wang Junhu , Kayes A.S.M. , Watters Paul A.
Published: July 2020

Nowadays, public gatherings and social events are an integral part of a modern city life. To run such events seamlessly, it requires real time mining and monitoring of causally related events so that the management can make informed decisions and take appropriate actions. The automatic detection of event causality from short text such as tweets could be useful for event management in this context. However, detecting event causality from tweets is a challenging task. Tweets are short, unstructured, and often written in highly informal language which lacks enough contextual information to detect causality. The existing approaches apply different techniques including hand‐crafted linguistic rules and machine learning models. However, none of the approaches tackle the issue related to the lack of contextual information. In this paper, we detect event causality in tweets by applying a context word extension technique and a deep causal event detection model. The context word extension technique is driven by background knowledge extracted from one million news articles. Our model achieves 79.35% recall and 67.28% f1‐score, which are 17.39% and 2.33% improvements to the state‐of‐the‐art approach.
Wearable sensor networks: A measurement study
Authors: Bujari Armir , Gaggi Ombretta , Palazzi Claudio E. , Quadrio Giacomo
Published: July 2020

Wearable technology is no longer science fiction. Thanks to the growing capability in the production chain to miniaturize complex electronics, a wide variety of gadgets that can be worn or included in dresses and accessories have emerged. These smart gadgets can collect data about the physical condition of the user and/or the environment providing the basis for innovative and valuable services. The main goal of this paper is to assess this context through field experiments undertaken in a testbed comprised of sensing hardware deployed on open source boards such as Arduino. Moreover, coupled with the sensing tier, we propose a proof‐of‐concept deployment architecture enabling a wide range of wearable sensors to collect and transmit data to a logically centralized unit.
Delayed approximate matrix assembly in multigrid with dynamic precisions
Authors: Murray Charles D. , Weinzierl Tobias
Published: July 2020

The accurate assembly of the system matrix is an important step in any code that solves partial differential equations on a mesh. We either explicitly set up a matrix, or we work in a matrix‐free environment where we have to be able to quickly return matrix entries upon demand. Either way, the construction can become costly due to nontrivial material parameters entering the equations, multigrid codes requiring cascades of matrices that depend upon each other, or dynamic adaptive mesh refinement that necessitates the recomputation of matrix entries or the whole equation system throughout the solve. We propose that these constructions can be performed concurrently with the multigrid cycles. Initial geometric matrices and low accuracy integrations kickstart the multigrid iterations, while improved assembly data is fed to the solver as and when it becomes available. The time to solution is improved as we eliminate an expensive preparation phase traditionally delaying the actual computation. We eliminate algorithmic latency. Furthermore, we desynchronize the assembly from the solution process. This anarchic increase in the concurrency level improves the scalability. Assembly routines are notoriously memory‐ and bandwidth‐demanding. As we work with iteratively improving operator accuracies, we finally propose the use of a hierarchical, lossy compression scheme such that the memory footprint is brought down aggressively where the system matrix entries carry little information or are not yet available with high accuracy.
Various syncretic co‐attention network for multimodal sentiment analysis
Authors: Cao Meng , Zhu Yonghua , Gao Wenjing , Li Mengyao , Wang Shaoxiu
Published: July 2020

The multimedia contents shared on social network reveal public sentimental attitudes toward specific events. Therefore, it is necessary to conduct sentiment analysis automatically on abundant multimedia data posted by the public for real‐world applications. However, approaches to single‐modal sentiment analysis neglect the internal connections between textual and visual contents, and current multimodal methods fail to exploit the multilevel semantic relations of heterogeneous features. In this article, the various syncretic co‐attention network is proposed to excavate the intricate multilevel corresponding relations between multimodal data, and combine the unique information of each modality for integrated complementary sentiment classification. Specifically, a multilevel co‐attention module is constructed to explore localized correspondences between each image region and each text word, and holistic correspondences between global visual information and context‐based textual semantics. Then, all the single‐modal features can be fused from different levels, respectively. Except for fused multimodal features, our proposed VSCN also considers unique information of each modality simultaneously and integrates them into an end‐to‐end framework for sentiment analysis. The superior results of experiments on three constructed real‐world datasets and a benchmark dataset of Visual Sentiment Ontology (VSO) prove the effectiveness of our proposed VSCN. Especially qualitative analyses are given for deep explaining of our method.
IKBKE, a prognostic factor preferentially expressed in mesenchymal glioblastoma, modulates tumoral immunosuppression through the STAT3/PD‐L1 pathway
Authors: Yi Li , Guo Gaochao , Li Jiabo , Fan Xiaoguang , Li Tao , Tong Luqing , Liu Peidong , Wang Xuya , Yuan Feng , Yu Shengping , Huang Qiang , Yang Xuejun
Published: July 2020

Inhibitor of nuclear factor kappa‐B kinase subunit epsilon (IKBKE) plays critical roles in the proliferation, invasion, and epithelial‐mesenchymal transition (EMT) of glioblastoma (GBM). However, as an immune response factor, few studies have focused on the role of IKBKE in the glioblastoma‐mediated immunosuppressive microenvironment. Here, we found a higher IKBKE expression level in gliomas corresponding to higher malignancy of the tumor. The highest level of IKBKE expression was examined in the core region of GBM tissues as well as the mesenchymal subtype, which are featured with necrosis, immunocyte infiltration, and immunosuppression. Further in silico analysis demonstrated that the JAK/STAT as the signaling pathway most associated with IKBKE in mesenchymal GBM. The co‐expression patterns of IKBKE, pSTAT3, and PD‐L1 were detected within GBM tissues. Mechanistically, IKBKE could interact with STAT3 and thus enhancing the phosphorylation level of STAT3 and its nuclear translocation. In addition, pSTAT3 could transcriptionally regulate the expression of PD‐L1 through binding to its promoter. In vivo results further confirmed the inhibitory effect of the IKBKE downregulation on tumor growth. Collectively, our findings suggest IKBKE as the central node in the crosstalk between NF‐κB and STAT3 signaling within mesenchymal GBM. Targeting GBM through inhibiting IKBKE could restrain tumor growth and tumor‐mediated immunosuppressive environment.
Tubulin post‐translational modifications control neuronal development and functions
Authors: Moutin Marie‐Jo , Bosc Christophe , Peris Leticia , Andrieux Annie
Published: July 2020

Microtubules (MTs) are an essential component of the neuronal cytoskeleton; they are involved in various aspects of neuron development, maintenance, and functions including polarization, synaptic plasticity, and transport. Neuronal MTs are highly heterogeneous due to the presence of multiple tubulin isotypes and extensive post‐translational modifications (PTMs). These PTMs—most notably detyrosination, acetylation, and polyglutamylation—have emerged as important regulators of the neuronal microtubule cytoskeleton. With this review, we summarize what is currently known about the impact of tubulin PTMs on microtubule dynamics, neuronal differentiation, plasticity, and transport as well as on brain function in normal and pathological conditions, in particular during neuro‐degeneration. The main therapeutic approaches to neuro‐diseases based on the modulation of tubulin PTMs are also summarized. Overall, the review indicates how tubulin PTMs can generate a large number of functionally specialized microtubule sub‐networks, each of which is crucial to specific neuronal features.
Detection of acquired von Willebrand syndrome after ventricular assist device by total thrombus‐formation analysis system
Authors: Takashio Seiji , Kaikita Koichi , Nishi Masato , Morioka Mami , Higo Taiki , Shiose Akira , Doman Tsuyoshi , Horiuchi Hisanori , Fukui Toshihiro , Tsujita Kenichi
Published: July 2020

Aims

Bleeding is a serious complication in patients with continuous‐flow left ventricular assist device (CF‐LVAD). Acquired von Willebrand syndrome (AVWS; type 2A) develops because of high shear stress inside the pumps and is a cause of bleeding complication. Although von Willebrand factor (vWF) multimer analysis is useful for diagnosing AVWS, it is only performed in specialized research institutes. A novel microchip flow chamber system, the total thrombus‐formation analysis system (T‐TAS), is a point‐of‐care system to evaluate the thrombus‐formation process and useful for monitoring platelet thrombus‐formation capacity in patients receiving antiplatelet therapy and the diagnosis and evaluation of the clinical severity of von Willebrand disease type 1. However, little is known about the association between AVWS and platelet thrombus‐formation capacity evaluated by T‐TAS in patients with CF‐LVAD. We aimed to evaluate the utility of T‐TAS for easy detection of AVWS in patients with CF‐LVAD.

Methods and results

We simultaneously evaluated the vWF large multimers and T‐TAS parameters in four consecutive patients with axial‐type CF‐LVAD and eight control patients treated with aspirin and warfarin. vWF large multimer index was defined as the proportion of large multimers in total vWF derived from a normal control plasma. T‐TAS analyses different thrombus‐formation processes using two microchips with different thrombogenic surfaces. PL24‐AUC10 levels in the platelet (PL) chip are highly sensitive for platelet functions, while AR10‐AUC30 levels in the atheroma (AR) chip allow the assessment of the overall haemostatic ability. vWF large multimer index and T‐TAS parameters were decreased in all patients with CF‐LVAD. The mean PL24‐AUC10 level (5.4 ± 2.9 vs. 219 ± 67; P < 0.01), AR10‐AUC30 level (338 ± 460 vs. 1604 ± 160; P < 0.01) and vWF large multimer index (49 ± 11% vs. 112 ± 27%; P < 0.01) were significantly lower in the patients with CF‐LVAD than in control patients. One patient showed changes in T‐TAS levels before and after implantation of CF‐LVAD. PL24‐AUC10 and AR10‐AUC30 levels decreased from 438.1 to 5.0 and from 1667.9 to 1134.3, respectively.

Conclusions

In patients with CF‐LVAD, the platelet thrombus‐formation capacity was extremely impaired because of AVWS, and T‐TAS parameters could detect the presence of AVWS. T‐TAS can be used for easy detection of AVWS as a point‐of‐care testing. Further studies with a large sample size are needed to validate our results in several LVAD models and evaluate the prognostic value of bleeding complications and thromboembolism in patients with LVAD.
Fibroblast‐derived IL‐33 is dispensable for lymph node homeostasis but critical for CD8 T‐cell responses to acute and chronic viral infection
Authors: Aparicio‐Domingo Patricia , Cannelle Hélène , Buechler Matthew B. , Nguyen Sylvain , Kallert Sandra M. , Favre Stéphanie , Alouche Nagham , Papazian Natalie , Ludewig Burkhard , Cupedo Tom , Pinschewer Daniel D. , Turley Shannon J. , Luther Sanjiv A.
Published: July 2020

Upon viral infection, stressed or damaged cells can release alarmins like IL‐33 that act as endogenous danger signals alerting innate and adaptive immune cells. IL‐33 coming from nonhematopoietic cells has been identified as important factor triggering the expansion of antiviral CD8+ T cells. In LN the critical cellular source of IL‐33 is unknown, as is its potential cell‐intrinsic function as a chromatin‐associated factor. Using IL‐33‐GFP reporter mice, we identify fibroblastic reticular cells (FRC) and lymphatic endothelial cells (LEC) as the main IL‐33 source. In homeostasis, IL‐33 is dispensable as a transcriptional regulator in FRC, indicating it functions mainly as released cytokine. Early during infection with lymphocytic choriomeningitis virus (LCMV) clone 13, both FRC and LEC lose IL‐33 protein expression suggesting cytokine release, correlating timewise with IL‐33 receptor expression by reactive CD8+ T cells and their greatly augmented expansion in WT versus ll33−/− mice. Using mice lacking IL‐33 selectively in FRC versus LEC, we identify FRC as key IL‐33 source driving acute and chronic antiviral T‐cell responses. Collectively, these findings show that LN T‐zone FRC not only regulate the homeostasis of naïve T cells but also their expansion and differentiation several days into an antiviral response.
Shining Light on TiIV Complexes: Exceptional Tools for Metallaphotoredox Catalysis
Authors: Fermi Andrea , Gualandi Andrea , Bergamini Giacomo , Cozzi Pier Giorgio
Published: July 2020

Titanium is one of the most abundant and environmentally innocuous metals. Ti‐based organometallic compounds have long been used as versatile homogeneous catalysts in synthetic chemistry and still remain highly attractive for the development of sustainable transformations. With the emerging role of photoredox catalysis, the selectivity of the radical initiation in electron transfer‐mediated reactions has been shown to be fundamental in terms of synthesis efficiency. Recent examples have displayed the effectiveness of inorganic and organic chromophores at the excited state in triggering the redox chemistry of TiIV/III complexes. In this minireview, we will illustrate the underlying principles and practicability of these – still uncommon – metallaphotoredox catalytic reactions.
Response of a scale‐model pile group for a jacket foundation of an offshore wind turbine in liquefiable ground during shaking table tests
Authors: Ko Yung‐Yen , Li Yi‐Ting
Published: July 2020

To investigate the seismic response of a pile group during liquefaction, shaking table tests on a 1/25 scale model of a 2 × 2 pile group were conducted, which were pilot tests of a test project of a scale‐model offshore wind turbine with jacket foundation. A large laminar shear box was utilized as the soil container to prepare a liquefiable sandy ground specimen. The pile group model comprising four slender aluminum piles with their pile heads connected by a rigid frame was designed with similitude considerations focusing on soil–pile interaction. The input motions were 2‐Hz sinusoids with various acceleration amplitudes. The excess pore water pressure generation indicated that the upper half of the ground specimen reached initial liquefaction under the 50‐gal‐amplitude excitation, whereas in the 75‐gal‐amplitude test, almost entire ground was liquefied. Accelerations in soil, on the movable frames composing the laminar boundary of the shear box, and along the pile showed limited difference at the same elevation before liquefaction. After liquefaction, the soil and the movable‐frame accelerations that represented the ground response considerably reduced, whereas both the movable frames and the piles exhibited high‐frequency jitters other than 2‐Hz sinusoid, and meantime, remarkable phase difference between the responses of the pile group and the ground was observed, all probably due to the substantial degradation of liquefied soil. Axial strains along the pile implied its double‐curvature bending behavior, and the accordingly calculated moment declined significantly after liquefaction. These observations demonstrated the interaction between soil and piles during liquefaction.
Modified model‐based control of shake tables for online acceleration tracking
Authors: Najafi Amirali , Spencer Billie F.
Published: July 2020

The interest in shake tables stems from a need to simulate earthquake behavior in laboratory settings. However, the inherent properties and nonlinearities associated with electromechanical and servohydraulic shake tables, combined with issues of table‐structure interaction, make accurate reproduction of earthquake acceleration time histories a challenging problem. The classical approach to control shake tables has been the Transfer Function Iteration (TFI) method. The tuning of the TFI controller is an offline iterative process, conducted using small amplitude ground motions. Effective compensation is not achievable for system nonlinearities that are not projected in the iterative tuning process. To address this problem, researchers have developed online compensation techniques, which can maintain tracking performance for the earthquake signals more effectively. Model‐based controllers (MBC) are a class of online controllers which use an identified model of the shake table‐structure for compensation. The MBC employs feedforward and feedback controllers to ensure that the shake table tracks a specified earthquake ground motion despite the presence of table and structural nonlinearities. However, the feedback controllers in MBC do not always maintain tracking accuracy and can result in loss of robustness when changes occur in the shake table and structure dynamics. This paper introduces a modified model‐based controller (mMBC) for acceleration tracking as an improvement on the existing MBC architecture. A stability condition is introduced to assess the robustness of the new modified control architecture. Through numerical and experimental studies, the improved tracking robustness of the mMBC architecture is demonstrated.
Sand settling through bedform‐generated turbulence in rivers
Authors: Yuill Brendan , Wang Yushi , Allison Mead , Meselhe Ehab , Esposito Chris
Published: July 2020

Fluvial bedforms generate a turbulent wake that can impact suspended‐sediment settling in the passing flow. This impact has implications for local suspended‐sediment transport, bedform stability, and channel evolution; however, it is typically not well‐considered in geomorphologic models. Our study uses a three‐dimensional OpenFOAM hydrodynamic and particle‐tracking model to investigate how turbulence generated from bedforms and the channel bed influences medium sand‐sized particle settling, in terms of the distribution of suspended particles within the flow field and particle‐settling velocities. The model resolved the effect of an engineered bedform, which altered the flow field in a manner similar to a natural dune. The modelling scenarios alternated bed morphology and the simulation of turbulence, using detached eddy simulation (DES), to differentiate the influence of bedform‐generated turbulence relative to that of turbulence generated from the channel bed. The bedform generated a turbulent wake that was composed of eddies with significant anisotropic properties. The eddies and, to a lesser degree, turbulence arising from velocity shear at the bed substantially reduced settling velocities relative to the settling velocities predicted in the absence of turbulence. The eddies tended to advect sediment particles in their primary direction, diffuse particles throughout the flow column, and reduced settling likely due to production of a positively skewed vertical‐velocity fluctuation distribution. Study results suggest that the bedform wake has a significant impact on particle‐settling behaviour (up to a 50% reduction in settling velocity) at a scale capable of modulating local suspended transport rates and bedform dynamics. © 2020 John Wiley & Sons, Ltd.
The response rate of alternative treatments for drugs approved on the basis of response rate
Authors: Haslam Alyson , Gill Jennifer , Prasad Vinay
Published: July 2020

We assessed the frequency that oncology drugs approved by the U.S. Food and Drug Administration (FDA) based on a single‐arm study when there is already evidence of existing and available treatments. For this, we conducted a retrospective cross‐sectional analysis of FDA‐approved oncology drugs based on a single‐arm study. All FDA announcements for all oncology drugs approved from May 2014 through June 2019 on a single‐arm trial were included. We then performed a systematic search in PubMed, looking for studies on other drugs for the same indication as the FDA drug approval. For the 60 indications, we found 38 instances (63%) of existing therapies being used for the same indication. Of those, we found that 20 drugs were approved based upon a response rate lower than response rates of existing therapies in the same indication. Among oncology drugs that were FDA‐approved based on a single‐arm study, we found evidence of existing, available therapies being used for the same indication as the FDA‐approved drug in the majority of indications (63%), and in one‐third of all indications, the response rates for existing therapies were numerically better than the FDA‐approved drug. These results suggest that there are inconsistencies in the standards set for oncology drug approvals, and many uncontrolled trials leading to drug approvals could have contemporary controls for which equipoise exists.
Banking market reaction to auctions of failed banks
Authors: Molyneux Philip , Zhou Tim Mi
Published: July 2020

In this study, we find that non‐merger rival banks of failed banks from 2008 to 2013 experience substantial negative abnormal stock returns in the United States when failed banks are auctioned. Negative abnormal returns are related to contagion effects associated with an increased probability of their own failure and the information of these rival banks' opaque assets. We also find evidence that FDIC resolutions of these failed banks, similar to previous regulatory interventions, distort the market competition.
Effect of misoprostol with and without letrozole on the induction of abortion for women with first‐trimester missed abortion
Authors: Allameh Zahra , Goharian Maryam , Eslamian Mohammad
Published: July 2020

Objective

To determine whether addition of letrozole to a misoprostol‐based abortion regimen can increase the rate of complete abortion.

Methods

The randomized, placebo‐controlled, double‐blind trial enrolled women with missed abortion in the first trimester of pregnancy attending Sadooghi Hospital, Isfahan, Iran, from 2016 to 2018. The women were randomly assigned to the study group, which received 10 mg of letrozole daily for 3 days, followed by two doses of 800 μg of vaginal misoprostol at a 4‐hour interval, or the control group, which received a placebo, followed by the same dose of misoprostol. Sonography was performed to check the abortion status.

Results

In total, 120 women completed the study: 60 in the misoprostol plus letrozole group, and 60 in the misoprostol only group. Complete abortion was documented for 93 (77.5%) women: 48 (80.0%) in the misoprostol plus letrozole group and 45 (75.0%) in the misoprostol only group (P=0.80). The mean duration of induction in the misoprostol plus letrozole and misoprostol only groups was 7.35 ± 3.54 hours and 8.2 ± 3.8 4hours, respectively (P=0.21).

Conclusion

Administration of misoprostol alone was found to be as effective as the administration of misoprostol plus letrozole for first‐trimester missed abortion.
English Disciplinary Literacy: Enhancing Students’ Literary Interpretive Moves
Authors: Reynolds Todd , Rush Leslie S. , Lampi Jodi P. , Holschuh Jodi Patrick
Published: July 2020

The authors explore foundational ideas of disciplinary literacy and articulate a research‐based heuristic for teaching disciplinary literacy in English language arts: generating, weaving, and curating. The authors apply the heuristic to the classroom, arguing that high school teachers should explicitly enhance students’ opportunities for low‐stakes interpretive moves by teaching them how to curate their own thoughts about texts and giving them the space and techniques to do so throughout their reading. The authors provide recommendations for expanding the focus of instruction from comprehension to interpretation, supporting students in developing their own interpretation through instructional techniques, such as journaling and discussion.
Combination of biocompatible hydrogel precursors to apatitic calcium phosphate cements (CPCs): Influence of the in situ hydrogel reticulation on the CPC properties
Authors: Ramirez Caballero Silvia Stella , Ferri‐Angulo Daniel , Debret Romain , Granier Fabien , Marie Sébastien , Lefèvre François‐Xavier , Bouler Jean‐Michel , Despas Christelle , Sohier Jérôme , Bujoli Bruno
Published: July 2020

In the field of bone regenerative medicine, injectable calcium phosphate cements (CPCs) are used for decades in clinics, as bone void fillers. Most often preformed polymers (e.g., hyaluronic acid, collagen, chitosan, cellulose ethers…) are introduced in the CPC formulation to make it injectable and improve its cohesion. Once the cement has hardened, the polymer is simply trapped in the CPC structure and no organic subnetwork is present. By contrast, in this work a CPC was combined with organic monomers that reticulated in situ so that a continuous biocompatible 3D polymeric subnetwork was formed in the CPC microstructure, resulting in a higher permeability of the CPC, which might allow to accelerate its in vivo degradation. Two options were investigated depending on whether the polymer was formed before the apatitic inorganic network or concomitantly. In the former case, conditions were found to reach a suitable rheology for easy injection of the composite. In addition, the in situ formed polymer was shown to strongly affect the size, density, and arrangement of the apatite crystals formed during the setting reaction, thereby offering an original route to modulate the microstructure and porosity of apatitic cements.
Multiomics data reveals the influences of myasthenia gravis on thymoma and its precision treatment
Authors: Ruan Xinjia , Lu Xiaofan , Gao Jun , Jiang Liyun , Zhu Yue , Zhou Yujie , Meng Jialin , Yan Hangyu , Yan Fangrong , Wang Fei
Published: July 2020

Thymoma is a rare characterized by a unique association with autoimmune diseases, especially myasthenia gravis (MG). However, little is known about the molecular characteristics of MG‐associated thymoma individuals. We aim to examine the influences of MG on thymoma by analyzing multiomics data. A total of 105 samples with thymoma was analyzed from TCGA and these samples were divided into subgroups with MG (MGT) or without MG (MGF) according to clinical information. We then characterized the differential gene expression, pathway activity, somatic mutation frequency, and likelihood of responding to chemotherapies and immunotherapies of the two identified subgroups. MGT subgroup was characterized by elevated inflammatory responses and metabolically related pathways, whereas the MGF subgroup was predicted to be more sensitive to chemotherapy and presented with mesenchymal characteristics. More copy number amplifications and deletions were observed in MGT, whereas GTF2I mutations occur at significantly higher frequencies in MGF. Two molecular subtypes were further identified within MGF samples by unsupervised clustering where one subtype was enriched in TGF‐β and WNT pathways with higher sensitivity to relevant targeted drugs but hardly respond to immunotherapy. For another subtype, a higher recurrence rate of thymoma and more likelihood of responding to immunotherapy were observed. Our findings presented a comprehensive molecular characterization of thymoma patients given the status of MG, and provided potential strategies to help individualized management and treatment.
Upregulation of histone H3K9 methylation in fetal endothelial cells from preeclamptic pregnancies
Authors: Sheng Wenji , Gu Yang , Chu Xiaodan , Morgan John A. , Cooper Danielle B. , Lewis David F. , McCathran Charles E. , Wang Yuping
Published: July 2020

Adverse intrauterine environment has been considered a predisposing factor for fetal programming in preeclampsia. Using human umbilical vein endothelial cells (HUVECs), we specifically explored if aberrant histone methylation occurs in fetal endothelial cells in preeclampsia. Strikingly, we found that increased di‐, and tri‐methylation of histone H3 lysine 9 (H3K9me2 and H3K9me3) expression were associated with upregulation of methyltransferase G9a and downregulation of endothelial nitric oxide synthase and CuZn‐SOD expression in preeclamptic HUVECs. We further demonstrated that hypoxia‐induced hypermethylation of H3K9 and reduced CuZn‐SOD expression mimicked what were seen in preeclamptic HUVECs and inhibition of G9a could attenuate these hypoxia‐induced adverse events. Our study was the first to identify hypermethylation status in fetal endothelial cells in preeclampsia, which provides plausible evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in fetal endothelial cells which may have a significant impact on fetal programming in preeclampsia.
Dental Decision Simulation (DDSim): Development of a virtual training environment
Authors: Johnson Kimberly S. , Schmidt Andrew M. , Bader James D. , Spallek Heiko , Rindal D. Brad , Enstad Chris J. , Fricton James R. , Asche Stephen E. , Kane Sheryl M. , Thirumalai Vijay , Godlevsky Olga V. , Johnson Neil J. , Acharya Amit , Rush William A.
Published: July 2020

Purpose

Case‐based simulations are powerful training tools that can enhance learning and drive behavior change. This is an overview of the design/development of Dental Decision Simulation (DDSim), a web‐based simulation of an electronic dental record (EDR). The purpose was to use DDSim to train dentists to make evidence‐based treatment planning decisions consistent with current evidence. This simulated EDR provides case‐based information in support of a set of defined evidence‐based learning objectives.

Methods

The development of this complex simulation model required coordinated efforts to create several components: identify behavior changes, case authoring mechanism, create virtual patient visits, require users to make treatment plan decisions related to learning objectives, and a feedback mechanism to help users recognize departures from those learning objectives. This simulation was evaluated in a 2‐arm, clinic‐randomized, controlled pilot study examining the extent to which DDSim changed dentists’ planned treatment to conform to evidence‐based treatment guidelines relative to change in dentists not exposed to DDSim. Outcomes were measured by comparing preintervention and postintervention patient EDR treatment data.

Results

Changes in behavior over time did not favor intervention or control clinics.

Conclusion

DDSim provides a standardized learning platform that cannot be achieved through the use of live patients. Both live patients and case‐based simulations can be used to transfer knowledge and skill development. DDSim offers the advantage of providing a platform for developing treatment planning skills in a low‐risk environment. However, further research examining behavior change is needed.
Teaching rapid oral health deterioration risk assessment: A 5‐year report
Authors: Craig Trevor , Johnsen David C. , Hartshorn Jennifer E. , Cowen Howard , Ashida Sato , Thompson Lena , Pendleton Chandler , Xie Xian Jin , Marchini Leonardo
Published: July 2020

Purpose/Objectives

The purpose of this study was to present a 5‐year report about the outcomes of using a teaching tool that guides dental students through the thought process of the expert about how to assess the risk of rapid oral health deterioration (ROHD) among older adults and provide viable treatment alternatives.

Methods

A teaching tool was previously developed using ROHD risk factors identified in the literature and the steps that experts apply in their treatment decision making, summarized in 10 questions. During 5 years, 188 senior dental students were introduced to the teaching tool and asked to use the 10‐question set to present a case they have treated during their Geriatric and Special Needs Program. Two evaluators were asked to grade the students on each question. Students were graded “G” if they answered the question and grasped the principles behind it, “A” if they only answered the question, or “M” if they missed the question. Additionally, the students were given a form to grade the importance of and comment on the exercise.

Results

More than 75% of the students had an A or G for most questions, agreement between the 2 evaluators was above 85%, and students’ performances improved during the 5‐year period. Additionally, 94.4% of the students considered the teaching tool as important or very important for the general dentist.

Conclusion

The vast majority of the students had an A or G grade, examiner agreement was high, and the students appreciated the importance of this teaching tool for the general dentist.
COVID‐19 diagnostics for resource‐limited settings: Evaluation of “unextracted” qRT‐PCR
Authors: Adams Nicholas M. , Leelawong Mindy , Benton Alison , Quinn Criziel , Haselton Frederick R. , Schmitz Jonathan E.
Published: July 2020

The coronavirus disease 2019 (COVID‐19) pandemic has created a precipitous increase in the need for molecular diagnostics. Unfortunately, access to RNA extraction reagents can represent a bottleneck for quantitative real‐time reverse transcriptase‐polymerase chain reaction (qRT‐PCR)‐based methodologies, stemming from both extraordinary supply‐chain stresses and the global reach of the virus into resource‐limited settings. To provide flexible diagnostic options for such environments, we report here an “unextracted modification” for qRT‐PCR using the Centers for Disease Control's (CDC's) widely utilized primers/probe sets for severe acute respiratory syndrome coronavirus 2 (N1/N2/N3 targeting viral nucleocapsid and RP‐control targeting human RNase P). This approach replaces RNA extraction/purification with a heat‐inactivation step of viral transport media (VTM), followed by direct inoculation—with or without VTM spin concentration—into PCR master mixes. Using derivatives of care from our clinical workflow, we compared traditional and unextracted CDC methodologies. Although some decrease in analytic sensitivity was evident (by higher Ct values) without extraction, in particular for the N2 primer/probe‐set, we observed high categorical positive agreement between extracted and unextracted results for N1 (unconcentrated VTM‐38/40; concentrated VTM‐39/41), N3 (unconcentrated VTM‐38/40; concentrated VTM‐41/41), and RP (unconcentrated and concentrated VTM‐81/81). The negative categorical agreement for N1/N2/N3 was likewise high. Overall, these results suggest that laboratories could adapt and validate unextracted qRT‐PCR protocols as a contingency to overcome supply limitations, with minimal impact on categorical results.
Analysis of the application value of serum antibody detection for staging of COVID‐19 infection
Authors: Zheng Yutong , Yan Meitian , Wang Lan , Luan Liang , Liu Jing , Tian Xiao , Wan Nan
Published: July 2020

Coronavirus disease 2019 (COVID‐19) has now spread all over the world. The National Health Commission of the People's Republic of China reported 78 439 cured and discharged cases, 4634 deaths, 83 462 confirmed cases and 760 818 close contacts as of 25 June 2020. Joint detection of nucleic acids and antibodies has become an important laboratory diagnostic for COVID‐19 patients. Disease progression and infection stage can be established based on the biological characteristics of these tests. However, there have been few studies of the different infection stages of COVID‐19. We conducted a retrospective analysis to explore the clinical characteristics of COVID‐19 patients at different infection stages and to characterize the characteristics of specific serum antibodies at each stage. These pieces of data will provide a theoretical basis for clinical diagnosis and treatment.