bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of high‐dimensional omics‐derived predictors for tumor growth dynamics using machine learning and pharmacometric modeling
Authors: Zwep Laura B. , Duisters Kevin L. W. , Jansen Martijn , Guo Tingjie , Meulman Jacqueline J. , Upadhyay Parth J. , van Hasselt J. G. Coen 
Published: April 2021

AbstractPharmacometric modeling can capture tumor growth inhibition (TGI) dynamics and variability. These approaches do not usually consider covariates in high‐dimensional settings, whereas high‐dimensional molecular profiling technologies (“omics”) are being increasingly considered for prediction of anticancer drug treatment response. Machine learning (ML) approaches have been applied to identify high‐dimensional omics predictors for treatment outcome. Here, we aimed to combine TGI modeling and ML approaches for two distinct aims: omics‐based prediction of tumor growth profiles and identification of pathways associated with treatment response and resistance. We propose a two‐step approach combining ML using least absolute shrinkage and selection operator (LASSO) regression with pharmacometric modeling. We demonstrate our workflow using a previously published dataset consisting of 4706 tumor growth profiles of patient‐derived xenograft (PDX) models treated with a variety of mono‐ and combination regimens. Pharmacometric TGI models were fit to the tumor growth profiles. The obtained empirical Bayes estimates‐derived TGI parameter values were regressed using the LASSO on high‐dimensional genomic copy number variation data, which contained over 20,000 variables. The predictive model was able to decrease median prediction error by 4% as compared with a model without any genomic information. A total of 74 pathways were identified as related to treatment response or resistance development by LASSO, of which part was verified by literature. In conclusion, we demonstrate how the combined use of ML and pharmacometric modeling can be used to gain pharmacological understanding in genomic factors driving variation in treatment response.
Bedload entrainment dynamics in a partially channelized river with mixed bedload: A case study of the Drava River, Hungary
Authors: Pirkhoffer Ervin , Halmai Ákos , Ficsor Johanna , Gradwohl‐Valkay Alexandra , Lóczy Dénes , Nagy Ádám , Liptay Zoltán Árpád , Czigány Szabolcs 
Published: April 2021

AbstractThe morphodynamics of alluvial rivers is controlled by the mobilization of bed material. However, the details of mobilization of mixed‐texture bed materials at low flows, increasingly common due to climate change, are still unclear. The 161‐km‐long Hungarian alluvial reach of the Drava River, downstream of sections where flow characteristics have been heavily modified by human interference, was investigated in 2019. A monitoring campaign at cross‐sections, on average 5.55 km apart, was launched to study channel morphology, bedload entrainment dynamics with regard to texture. For the survey, a sonar, an ADCP and a Helley–Smith bedload sampler mounted on a double‐hull vessel was used. Our research pointed out an abrupt fining between river kms (hereafter: rkm) 175 and 170 (distance from the mouth), probably due to reduced armouring. The d60 fraction was found to be finer than in 2003 and 2012 for the upstream stations of Botovo and Bélavár, and showed a good correspondence with the records of the Barcs and Drávaszabolcs stations. Temporal fining and higher entrainment rate are due to (a) changing climate of the catchment, that is, diminishing flow between the monitoring dates (2003, 2012 and 2019); (b) reduced armouring, (c) variability of cross‐sectional position of sampling points and (d) the different mesh size of the bedload samplers employed. Calculations of shear velocity, Reynolds and Shields numbers indicate more dynamic sediment motion than observed by previous studies. Our reach‐scale results may be relevant for the alluvial sections of other alpine and subalpine, partially channelized rivers of similar size, flow dynamics and mixed bedload.
Mesenchymal Stem Cells and Three-Dimensional-Osteoconductive Scaffold Regenerate Calvarial Bone in Critical Size Defects in Swine
Authors: Johnson Zoe M. , Yuan Yuan , Li Xiangjia , Jashashvili Tea , Jamieson Michael , Urata Mark , Chen Yong , Chai Yang 
Published: April 2021

Abstract
Craniofacial bones protect vital organs, perform important physiological functions, and shape facial identity. Critical-size defects (CSDs) in calvarial bones, which will not heal spontaneously, are caused by trauma, congenital defects, or tumor resections. They pose a great challenge for patients and physicians, and significantly compromise quality of life. Currently, calvarial CSDs are treated either by allogenic or autologous grafts, metal or other synthetic plates that are associated with considerable complications. While previous studies have explored tissue regeneration for calvarial defects, most have been done in small animal models with limited translational value. Here we define a swine calvarial CSD model and show a novel approach to regenerate high-quality bone in these defects by combining mesenchymal stem cells (MSCs) with a three-dimensional (3D)-printed osteoconductive HA/TCP scaffold. Specifically, we have compared the performance of dental pulp neural crest MSCs (DPNCCs) to bone marrow aspirate (BMA) combined with a 3D-printed HA/TCP scaffold to regenerate bone in a calvarial CSD (&gt;7.0 cm2). Both DPNCCs and BMA loaded onto the 3D-printed osteoconductive scaffold support the regeneration of calvarial bone with density, compression strength, and trabecular structures similar to native bone. Our study demonstrates a novel application of an original scaffold design combined with DPNCCs or BMA to support regeneration of high-quality bone in a newly defined and clinically relevant swine calvarial CSD model. This discovery may have important impact on bone regeneration beyond the craniofacial region and will ultimately benefit patients who suffer from debilitating CSDs.
Efficient Adsorption of Doxycycline Hydrochloride Using Deep Eutectic Solvent Functionalized Activated Carbon Derived from Pumpkin Seed Shell
Authors: Kaur Gurleenjot , Singh Neetu , Rajor Anita 
Published: April 2021

AbstractThe emerging deep eutectic solvents (DESs) are being utilized in different areas of science and engineering due to their exceptional physicochemical properties. In this study, choline chloride‐based DES was prepared in conjugation with glycolic acid (GA) as a hydrogen bond donor (HBD). Activated carbon was derived from pumpkin seed shell (PSS) using microwave‐assisted pyrolysis technique in an N2 environment. The potential of synthesized DES was evaluated as a functionalization agent for PSSAC. DES functionalized PSSAC (DES‐PSSAC) was characterized using FTIR, XRD, FESEM and BET surface area to confirm the functionalization and identify the physico‐chemical changes. This prepared DES‐PSSAC was used as an adsorbent for the uptake of Doxycycline hydrochloride (DOX) from its aqueous solution. The influence of different process parameters was inspected in order to determine the optimal experimental conditions. At optimized parameters, the kinetics and thermodynamics studies were explored. Used DES was confirmed to be effectively grafted onto the PSSAC surface. The experimental data, best suited to the Pseudo second‐order kinetic model, whereas adsorption isotherm data were best represented by Freundlich and R‐P isotherm models. The recorded maximum adsorption capacity (qmax) was found to be 30.35 mg/g. High adsorption performance of DES‐PSSAC towards DOX uptake and its reusability exhibited that this novel adsorbent can be applied to remove pharmaceutical pollutants.
Pyridine Derivatives as Biologically Active Precursors; Organics and Selected Coordination Complexes
Authors: Khan Ezzat 
Published: April 2021

AbstractPyridine (py) is an important heterocyclic compound and is an integral part of various natural products. There are various medicines containing py ring system being available in the market to combat different human ailments. Observing the medicine market, Omeprazole, a widely used py‐based drug in medicinal market since 1998. Netupitant (an antiemitic drug, since 2014) is used in combination with another drug to prevent acute and delayed vomiting and nausea associated with cancer chemotherapy led the run towards development of anticancer drugs. Several drugs have been approved by FDA for the treatment of cancer in recent years such as, Abemaciclib (2015), Lorlatinib (2018), Apalutamide (2018) and Ivosidenib (2019). Research on py on the bases of these advancements is an evergreen field and associated with greater hopes to address several disease related issues. Several compounds are in the process of clinical trials and are expected to serve various purposes in days to come. This review article deals with recent findings in py chemistry and its coordination complexes. The medicinal efficiency has been argued for organic and inorganic derivatives. Selected biological applications are hereby discussed as follow up study of our report in 2015. Suitable literature prior to 2015 has also been incorporated in appropriate places in order to cover the scope in broader sense.
Improved Practical Synthesis of DY‐038, an Oral Available Antiplatelet Agent
Authors: Cao Yangzhi , Kong Deyu , Sun Lulu , Meng Xin , Zhang Yinyong , Guo Bin , Yang Yushe 
Published: April 2021

AbstractRecently, we reported the promising activity of a series of novel bicyclic pyridine derivatives as antiplatelet agents. Herein, we describe a modified and improved chemical synthesis of the lead compound, 1‐(3‐cyano‐5‐oxo‐5,7‐dihydrofuro[3,4‐b]pyridin‐2‐yl)‐4‐methyl‐N‐((4‐methylbenzyl)sulfonyl)piperidine‐4‐carboxamide (1), with the aim to produce from milligrams to 10 g of the pure compound that is necessary for the preclinical studies. This novel process is one step shorter and starts from cheap materials, achieving a sevenfold of the total yield from 0.7 % to 5 %. Additionally, it also avoids the use of palladium on carbon as well as all of the steps involve simple purifications without chromatography.
Experimental research and mechanical analysis on the bond‐slip behavior between concrete and corroded I‐shaped steel
Authors: Zhang Yiteng , Wang Mingnian , Yu Li , Guo Xiaohan , Liu Kerui , Yang Henghong 
Published: April 2021

AbstractCorrosion of I‐shaped steel in the primary support of the subsea tunnel is inevitable due to high chloride ion content, which will weaken the bond performance between concrete and I‐shaped steel, resulting in a reduction in the service time of the subsea tunnel. Based on Xiang'an subsea tunnel, the bond–slip behavior between concrete and corroded I‐shaped steel was studied by the accelerated corrosion tests and push‐out tests, the experimental results indicated that: (1) The cracks of experimental specimens could be divided into two main forms: splitting failure (corrosion rate less than 5.79%); spalling failure (corrosion rate more than 5.79%). (2) A three‐stage bond‐slip law for concrete and corroded I‐shaped steel was proposed, and the formulae for calculating the bond strength were established. Furthermore, the degradation process of bond‐slip caused by corrosion was analyzed by energy principle and damage mechanics. Based on energy principle, it found that the elastic energy stored in the interface increased before the peak point of bond‐slip curve and decreased after the peak point, while the dissipated energy in the interface always increased with slip value. Finally, the interface relative damage variable was defined based on secant line anti‐sliding modulus and slip equivalent principle. The interface damage development process can be divided into three stages: initial damage, rapid damage development, and slow damage accumulation.
ROCK inhibitor attenuates carbon blacks‐induced pulmonary fibrosis in mice via Rho/ROCK/NF‐kappa B pathway
Authors: Yan Junyan , Tang Yaxin , Zhong Xin , Huang Huarong , Wei Haonan , Jin Yulei , He Yanjiang , Cao Jinqiao , Jin Lifang , Hu Baowei 
Published: April 2021

AbstractExposure to carbon blacks (CBs) has been associated with the progression of pulmonary fibrosis, whereas the mechanism is still not clear. We therefore aimed to investigate the effect of RhoA/ROCK pathway on pulmonary fibrosis caused by CBs exposure. Western blot analysis indicated that CBs could promote the activation of RhoA/ROCK pathway and phosphorylation of p65 and IκBα in mice lung. However, ROCK inhibitor Y‐27632 could attenuate phosphorylation levels of p65 and IκBα and restore histopathological changes of the lung tissue. Then, we evaluated the effect of RhoA/ROCK pathway on pulmonary fibrosis by detecting the expression levels of α‐SMA, vimentin, and Collagen type‐I (Col‐I), which could be partly inhibited by Y‐27632. It was assumed that inhibition of ROCK could be a promising therapeutic candidate for CBs‐induced pulmonary fibrosis, which possibly through the blockage of RhoA/ROCK/NF‐κB pathway.
Prevention of cognitive decline in subjective cognitive decline APOE ε4 carriers after EGCG and a multimodal intervention (PENSA): Study design
Authors: Forcano Laura , Fauria Karine , Soldevila‐Domenech Natalia , Minguillón Carol , Lorenzo Thais , Cuenca‐Royo Aida , Menezes‐Cabral Sofia , Pizarro Nieves , Boronat Anna , Molinuevo José Luis , Torre Rafael de la ,   PENSA Study Groupǂ
Published: April 2021

AbstractIntroductionSubjects exhibiting subjective cognitive decline (SCD) are at an increased risk for mild cognitive impairment and dementia. Given the delay between risk exposure and disease onset, SCD individuals are increasingly considered a good target population for cost‐effective lifestyle‐based Alzheimer's disease prevention trials.MethodsThe PENSA study is a randomized, double‐blind, controlled clinical trial that aims to evaluate the efficacy of a personalized multimodal intervention in lifestyle (diet counseling, physical activity, cognitive training, and social engagement) combined with the use of epigallocatechin gallate (EGCG) over 12 months, in slowing down cognitive decline and improving brain connectivity. The study population includes 200 individuals meeting SCD criteria and carrying the apolipoprotein E ε4 allele, who will be randomized into four treatment arms (multimodal intervention + EGCG/placebo, or lifestyle recommendations + EGCG/placebo). The primary efficacy outcome is change in the composite score for cognitive performance measured with the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS‐PACC‐like) adding to the original version the Interference score from the Stroop Color and Word Test and the Five Digit Test. Secondary efficacy outcomes are (1) change in functional magnetic resonance imaging (fMRI) and structural neuronal connectivity (structural MRI) and (2) the safety assessment of the EGCG compound. This study is framed within the WW‐FINGERS consortium.DiscussionThe use of new technologies (i.e., mobile ecological momentary assessments [EMAs], activity tracker) in the PENSA study allows the collection of continuous data on lifestyle behaviors (diet and physical activity) and mood, enabling a personalized design as well as an intensive follow‐up of participants. These data will be used to give feedback to participants about their own performance along the intervention, promoting their involvement and adherence. The results of the study may aid researchers on the design of future clinical trials involving preventive lifestyle multicomponent interventions.
Numerical Platform
Authors: Yoshioka Keita , Nest Mathias , Pötschke Daniel , Sattari Amir Shoarian , Schmidt Patrick , Krach David 
Published: April 2021

AbstractAn essential scientific goal of the GeomInt project is the analysis of potentials and limitations of different numerical approaches for the modelling of discontinuities in the rocks under consideration in order to improve the understanding of methods and their synergies with regard to theoretical and numerical fundamentals. As numerical methods, the “Lattice Element Method” (LEM), the non-continuous discontinuum methods “Discrete Element Method” (DEM), the “Smoothed Particle Hydrodynamics” (SPH), the “Forces on Fracture Surfaces” (FFS) as well as the continuum approaches “Phase-Field Method” (PFM), “Lower-Interface-Method” (LIE), “Non-Local Deformation” (NLD) and the “Hybrid-Dimensional Finite-Element-Method” (HDF) will be systematically investigated and appropriately extended based on experimental results (Fig. 3.1).
The Promise of Non-arm’s Length Practices: Is the Destination-Based Cash Flow Tax or Unitary Taxation the Panacea of Which Developing Countries Are in Search?
Authors: Titus Afton 
Published: April 2021

AbstractThe issues developing countries face when implementing the arm’s length standard are well known. As a result, the time seems opportune for an alternative paradigm. The unitary taxation system has received considerable attention and comment over the last few years as such an alternative. Some have heralded it as the answer to the many problems brought about by the arm’s length standard. Moreover, some suggest that the destination-based cash flow taxation system is the panacea to the present problems in international tax arising from the prevailing approach to the taxation of global affiliated companies. This article tests whether the destination-based cash flow tax and unitary taxation system continue to hold promise when applied in an African context.
Development of a Low-Cost, High Accuracy, Flexible Panel Indexing Cell with Modular, Elastic Architecture
Authors: Brownbill Robert , Roberts Adam 
Published: April 2021

AbstractThe global aerospace industry is driving a demand for flexible manufacturing systems to accommodate multiple programs with variable capacities within a modular, economical production cell [1]. Traditional manufacturing cells often involve bespoke, monolithic hardware limited to single program use. This inherent restraint results in significant incurred costs and program disruption when reacting to design and capacity changes. This paper describes the development of a reconfigurable panel-indexing cell with a dynamic cost architecture as an alternative approach to established, monolithic tooling structures.
Context-Aware Plug and Produce for Robotic Aerospace Assembly
Authors: Sanderson David , Shires Emma , Chaplin Jack C. , Brookes Harvey , Liaqat Amer , Ratchev Svetan 
Published: April 2021

AbstractAerospace production systems face increasing requirements for flexibility and reconfiguration, along with considerations of cost, utilisation, and efficiency. This drives a need for systems with a small number of automation platforms (e.g. industrial robots) that can make use of a larger number of end effectors that are potentially flexible or multifunctional. This leads to the challenge of ensuring that the configuration and location of each end effector is tracked by the system at all times, even in the face of manual adjustments, to ensure that the correct processes are applied to the product at the right time. We present a solution based on a Data Distribution Service that provides the system with full awareness of the context of its automation platforms and end effectors. The solution is grounded with an example use case from WingLIFT, a research programme led by a large aerospace manufacturer. The WingLIFT project in which this solution was developed builds on the adaptive systems approach from the Evolvable Assembly Systems project, with focus on extending and increasing the aerospace industrial applicability of plug and produce techniques. The design of this software solution is described from multiple perspectives, and accompanied by details of a physical demonstration cell that is in the process of being commissioned.
Towards Human and Robot Collaborative Ergonomic Handling of Long Parts with a Loose Grip
Authors: Hofmann Michael , Ganglbauer Markus , Propst Matthias , Wögerer Christian , Pichler Andreas 
Published: April 2021

AbstractThe concept of robots collaborating with humans has gained a lot of interest in the recent years. The pure use of the robot to follow the human’s actions involves several important components, which have to fullfil economic, ergonomic, safety and usability aspects. This paper presents a setup build with recent hardware and taking economic, safety and usability aspects into account. A concept is introduced how the ergonomics of a human worker is actively influenced by the system.
Assistance Needs in Production Environments: A Contextual Exploration of Workers’ Experiences and Work Practices
Authors: Meneweger Thomas , Fuchsberger Verena , Gerdenitsch Cornelia , Egger-Lampl Sebastian , Tscheligi Manfred 
Published: April 2021

AbstractThis paper presents assistance needs in production environments for assembly processes from a workers’ perspective, i.e. what kind of assistance assembly workers would need to enhance their everyday work experience and to better cope with challenges coming along with an increasing digitization in these work environments. Within a large-scale empirical field study in central Europe, we interviewed assembly workers and observed everyday work situations in different production environments (e.g., automotive domain) to understand workers’ experiences and work practices in increasingly connected and automated production environments. Based on the insights gained in this study, we describe several assistance needs for assembly workers that serve as a guidance for future worker-centric designs of assistance systems in production environments.
The Consideration of Job Satisfaction in the Design of Assistance Systems in Production
Authors: Damalas Stelios , Neuhuber Norah , Mörtl Peter 
Published: April 2021

AbstractAssistance systems designed to help workers in their jobs are increasingly used in industry. Technological progress makes these systems more powerful and extensive, but often nobody questions the extent to which they actually support the users and do not patronize them. For the development of such systems, we found the requirement analysis to be rather complex because human factors and social constraints are more difficult to determine than technical requirements. To counteract these difficulties, we pursue in our approach the involvement of people as knowledge carriers in the development of new technologies. In this paper we outline our framework how human factors aspects of acceptance and job satisfaction can be taken into account in the conception and design of assistance systems.
Strategies for Dealing with Problems in Robotised Unscrewing Operations
Authors: Huang Jun , Pham Duc Truong , Li Ruiya , Jiang Kaiwen , Lyu Dalong , Ji Chunqian 
Published: April 2021

AbstractDisassembly is the first step in a remanufacturing process chain with unscrewing being usually the most frequent task. In previously reported research in the authors’ laboratory, a new method has been developed for using robots to unfasten screws. Uncertainties and variability in the physical condition of screws induced by dirt, rust, or mechanical damage pose difficulties for such robotised unscrewing systems. There are three common failure modes: screwdriver missing screw head, screwdriver slipping on screw head and screw too tight to remove. This paper presents strategies to handle these failure modes, making the developed robotised method more robust and reliable. The strategies include conducting a second search and second unfastening trial as well as involving collaboration with a human operator. Tests were carried out to validate the proposed strategies. The results show that the strategies could deal with the failure modes, enabling 100% successful operation.