bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of human plasma lipoproteins using anion exchange fast protein liquid chromatography and targeted mass spectrometry assay
Authors: Seidl Claudia , Flaten Zachary , Li Danni 
Published: January 2021

AbstractWe described a targeted mass spectrometry assay based on selected reaction monitoring (SRM) for five apolipoproteins (apoA1, apoB, apoJ, apoD, and apoE) in plasma lipoproteins isolated by anion exchange fast protein liquid chromatography using only 100 μL of plasma. We performed analytical characterization of the SRM assay and evaluated reproducibility of the entire workflow. The limit of detections for apoA1, apoB, apoD, apoJ, and apoE were 0.6, 4.6, 0.8, 1.2, and 0.7 nM, respectively; the limit of quantifications was 8.3 nM for all peptides except apoD (4.2 nM). The SRM assay was linear from 0.4 to 1667 nM. The intra‐day and inter‐day and total repeatability (CV%) of the assay ranged from 2.2% to 21.7% for all five peptides. The intra‐day and inter‐day and total reproducibility of the entire workflow ranged from 12.2% to 43.9% for all five peptides in fractionated high‐density lipoprotein, low‐density lipoprotein, and IDL. In the future, we will apply this workflow to investigate the association of fractionated plasma lipoproteins with amyloid deposition and cognitive changes in the context of Alzheimer's disease.
Computational investigation of KICl2 iodination of thiophene and its electron‐poor derivatives
Authors: Sarkar Akash Mamon , Sereda Grigoriy A. , Miró Pere 
Published: January 2021

AbstractElectrophilic iodination of thiophene and its electron‐poor derivatives has been studied with KICl2 in dichloromethane and methanol using density function theory. KICl2 easily dissociates forming KCl and ICl, the latter being the iodinating agent. ICl forms an adduct with thiophene (π‐complex) followed by a nucleophilic attack of the ICl component by the aromatic component that forms the C–I bond. The nucleophilic attack is always the rate determining step with higher barriers that are in agreement the experimental conditions required for this reaction. The abstraction of a proton by the chloride anion on the last step is barrierless leading to the mono‐ and di‐iodination of the thiophene derivatives. Side products derived from the nucleophilic addition of the chloride anion have been determined to be transient.
Chemokine Receptor 2 Targeted Gold Nanocluster Imaging Triple Negative Breast Cancer with Positron Emission Tomography
Authors: Zhao Yongfeng , You Meng , Detering Lisa , Sultan Deborah , Luehmann Hannah , Liu Yongjian 
Published: January 2021

AbstractDue to the lack of effective biomarker and specific diagnosis, triple negative breast cancer (TNBC) patients frequently suffer early‐onset relapse and metastasis after conventional therapy, leading to overall poor survival. It is crucial to develop targeted approaches for accurate TNBC detection and drug delivery to improve patient survival. Herein, the potential of chemokine (C‐C motif) receptor 2 (CCR2) as a biomarker for TNBC is characterized. Through a 64Cu radiolabeled CCR2 targeting peptide radiotracer, the presence of CCR2 in TNBC is specifically imaged using positron emission tomography in a mouse 4T1 TNBC model, which is further confirmed by western blot, immunostaining, and reverse transcription polymerase chain reaction analysis. Through a well‐defined and straightforward radioactive synthesis, an ultrasmall gold nanocluster intrinsically radiolabeled with 64Cu is prepared for CCR2 targeted imaging in 4T1 tumor‐bearing mice. Time‐course study and quantitative uptake analysis reveal significantly improved tumor targeting efficiency and tumor‐to‐background contrast ratio compared to peptide tracer alone. Taken together, it is believed CCR2 is a useful biomarker for TNBC, and the targeted nanocluster can serve as a useful platform for sensitive and accurate diagnosis of TNBC.
Pharmacodynamic analysis of hypertension caused by lenvatinib using real‐world postmarketing surveillance data
Authors: Otani Yuki , Kasai Hidefumi , Tanigawara Yusuke 
Published: January 2021

AbstractLenvatinib is a tyrosine kinase inhibitor of the vascular endothelial growth factor receptor used against nonoperative thyroid cancer; however, hypertension is a major dose‐limiting side effect. In this study, hypertension caused by lenvatinib was described through a novel population pharmacodynamic model using postmarketing surveillance data obtained in Japan. The model consists of two maximum effect model components based on the (1) concentration of lenvatinib in plasma and (2) cumulative area under the curve of lenvatinib. In addition, antihypertensive drug of either an angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker or calcium channel blocker accounted for by lowering effect on diastolic blood pressure. Based on virtual simulations, the combination of antihypertensive drug and dose adjustment of lenvatinib showed a reduction in the probability of grade greater than or equal to 3 hypertension. The present model provides useful guidance in managing hypertension during treatment with lenvatinib in the real‐world setting.
Regression‐adjusted Poisson EWMA control chart
Authors: Wen Hongling , Liu Liu , Yan Xinlong 
Published: January 2021

AbstractExponentially weighted moving average (EWMA) control chart has a significant effect in improving product quality and is widely used in various fields. In addition to continuous data, there are many Count Data in life that need to be monitored. Poisson distribution is one of the models that study the probability distribution of discrete data, and has a wide range of applications. In previous monitoring, it was considered that the mean value of Poisson distribution in normal state was a constant value after it was determined. But in the actual situation, there are many unavoidable objective conditions that will affect the final results. We cannot monitor all situations according to the same criteria. If we ignore the conditions that affect the occurrence of the event and directly monitor the final result, on the one hand, it will increase the probability of false alarms from the control chart. On the other hand, the control chart will not be able to detect problems in time due to the untimely update of conditions. In response to this situation, this paper proposes a regression‐adjusted EWMA control chart to monitor the Poisson process. The control chart can continuously adjust and update the expected values according to the actual situation. It can make the monitoring process more reasonable and the monitoring results more valuable.
A side‐sensitive synthetic coefficient of variation chart
Authors: Yeong Wai Chung , Lee Ping Yin , Lim Sok Li , Khaw Khai Wah , Khoo Michael Boon Chong 
Published: January 2021

AbstractControl charts for monitoring the coefficient of variation (γ) are useful for processes with an inconsistent mean (μ) and a standard deviation (σ) which changes with μ, by monitoring the consistency in the ratio σ over μ. The synthetic‐γ chart is one of the charts proposed to monitor γ, and its attractiveness lie in waiting until a second point to fall outside the control limits before a decision is made. However, existing synthetic‐γ charts do not differentiate between the points falling outside the upper control limit (UCL) and lower control limit (LCL). Hence, this paper proposes a side‐sensitive synthetic‐γ chart, where successive nonconforming samples must either fall above the UCL or below the LCL. Formulae to compute the average run length (ARL), the standard deviation of the run length (SDRL) and expected average run length (EARL) are derived using the Markov chain approach, and the algorithms to obtain the optimal charting parameters are proposed. Subsequently, the optimal charting parameters, ARL, SDRL and EARL values for various numerical examples are shown. Comparisons show that the side‐sensitive synthetic‐γ chart consistently outperforms the existing synthetic‐γ chart, especially for small shifts. The proposed chart also consistently outperforms the Shewhart‐γ chart, while showing comparable or better performance than the Exponentially Weighted Moving Average (EWMA) chart for most shift sizes, except for very small shifts. Finally, this paper shows the implementation of the proposed chart on an industrial example.
Enantio‐separation of pregabalin by ternary complexation using trapped ion mobility spectrometry
Authors: Gu Liancheng , Yang Shutong , Wu Fangling , Xu Fuxing , Yu Shaoning , Zhou Mingfei , Chu Yanqiu , Ding Chuan‐Fan 
Published: January 2021

RationaleThe rapid identification of small‐molecule chiral drugs is challenging due to subtle structural differences. Different enantiomers of chiral drugs may produce inverse biological effects through their different pharmacokinetics. Therefore, it is highly desirable to distinguish the chirality of drug molecules.MethodsThe chirality of pregabalin was distinguished by studying the ion mobility spectra of the ternary non‐covalent complexes formed with cyclodextrins (CDs), pregabalin, and alkali‐earth cations using trapped ion mobility spectrometry (TIMS). The ternary non‐covalent complex ions were determined by electrospray ionization of mixed solutions. The analyzed sample was simply mixed, without derivatization or sample pretreatment. The relative contents of pregabalin enantiomers were derived using a calibration curve method.ResultsThe ion mobility spectra of several ternary non‐covalent complexes formed with α‐, β‐, and γ‐CD, pregabalin, and alkali‐earth cations were obtained. We compared their ability to distinguish the chirality of pregabalin. The best peak‐to‐peak resolution (Rp‐p) was estimated to be 2.20 for [2β‐CD + pregabalin + Sr]2+, which can be ascribed as baseline separation. The derived relative contents for S‐pregabalin were in agreement with the actual contents.ConclusionsA novel and convenient method for discriminating the chirality of the pregabalin molecule by TIMS was developed and optimized. The chirality of pregabalin was recognized by studying the ion mobility spectra of the ternary non‐covalent complexes, such as [2β‐CD + pregabalin + Sr]2+. This TIMS method could also be used to quantify the relative contents of pregabalin enantiomers.
Research on spatial motion safety constraints and cooperative control of robot‐assisted craniotomy: Beagle model experiment verification
Authors: Xu Cheng , Lin Li , Mar Aung Zin , Chai Gang , Xie Le 
Published: January 2021

AbstractBackgroundTraditional craniotomy depends primarily on the experience of the surgeon. However, the accuracy of manual operation is limited and carries certain surgical risks. The interaction method of current robot‐assisted craniotomy is unnatural and inadaptive to the operating style of the surgeon. In this research, we built a hands‐on synergistic robotics craniotomy system with human–machine collaboration. Safe isometric surfaces and virtual restraint methods are combined to achieve highly accurate, efficient, minimally invasive and safe craniotomy.Materials and methodsFifteen three‐dimensional (3D)‐printed beagle skull models were used to evaluate the system accuracy and the related image guidance process. It mainly includes the design of the surgical plan, the adopted strategy based on motion constraint and safe isometric surface, and the impedance control method based on the position inner loop via the human–machine collaboration method. The trajectory tracking experiment was performed by applying human–machine collaboration, and completed an experiment on the 3D‐printed beagle skull models involving drilling and milling of the skull performed by the robot, and evaluation of accuracy via computed tomographic (CT) scanning verification after the operation.ResultsThe 3D‐printed beagle skull model experiment shows that the average errors for the top surface and the bottom surface, and the angle error were 0.81 ± 0.15 mm, 0.89 ± 0.12 mm, and 1.74° ± 0.16°, respectively. The average milling position errors for the top and bottom surfaces were 0.87 ± 0.19 and 0.93 ± 0.22 mm, respectively.ConclusionThe performance of the robot system was evaluated and verified using a 3D‐printed beagle model experiment. The proposed collaborative surgical robot system is feasible and can complete a craniotomy, with improved accuracy and surgical safety.
Engineering the Near‐Surface of PtRu3 Nanoparticles to Improve Hydrogen Oxidation Activity in Alkaline Electrolyte
Authors: Zhang Junming , Qu Ximing , Shen Linfan , Li Guang , Zhang Tianen , Zheng Jinhong , Ji Lifei , Yan Wei , Han Yu , Cheng Xiaoyang , Jiang Yanxia , Sun Shigang 
Published: January 2021

AbstractTailoring the near‐surface composition of Pt‐based alloy can optimize the surface chemical properties of a nanocatalyst and further improve the sluggish H2 electrooxidation performance in an alkaline electrolyte. However, the construction of alloy nanomaterials with a precise near‐surface composition and smaller particle size still needs to overcome huge obstacles. Herein, ultra‐small PtRu3 binary nanoparticles (<2 nm) evenly distributed on porous carbon (PtRu3/PC), with different near‐surface atomic compositions (Pt‐increased and Ru‐increased), are successfully synthesized. XPS characterizations and electrochemical test confirm the transformation of a near‐surface atomic composition after annealing PtRu3/PC‐300 alloy; when annealing in CO atmosphere, forming the Pt‐increased near‐surface structure (500 °C), while the Ru‐increased near‐surface structure appears in an Ar heat treatment process (700 °C). Furthermore, three PtRu3/PC nanocatalysts all weaken the hydrogen binding strength relative to the Pt/PC. Remarkably, the Ru‐increased nanocatalyst exhibits up to 38.8‐fold and 9.2‐fold HOR improvement in mass activity and exchange current density, compared with the Pt/PC counterpart, respectively. CO‐stripping voltammetry tests demonstrate the anti‐CO poisoning ability of nanocatalysts, in the sequence of Ru‐increased ≥ PtRu3/PC‐300 > Pt‐increased > Pt/PC. From the perspective of engineering a near‐surface structure, this study may open up a new route for the development of high‐efficiency electrocatalysts with a strong electronic effect and oxophilic effect.
Dealing with complexity by using multilevel system boundary models
Authors: Pinzon‐Salcedo Luis Arturo , Bernal‐Alvarado Juanita 
Published: January 2021

AbstractIncreasingly, researchers and practitioners operate in complex systems difficult to comprehend. In them, the multiplicity of perspectives, elements and relationships operating on multiple levels makes the practice of systems thinking and boundary critique considerably difficult. Drawing upon boundary critique and hierarchy theory, this paper presents ways of thinking in terms of multilevel boundary judgements models useful for addressing the aforementioned problem in all fields of study. A real example of the use of these models is presented. This paper also discusses how thinking in terms of multiple levels of boundary judgements is important to better deal with values and moral frameworks and to promote critical reflexivity in systemic interventions, while escaping the dangers of reductionism. Furthermore, a systemic way of exploring the role of moral frameworks in systems practice is discussed, contributing with new concepts useful to develop a deeper understanding of ethical issues in systems practice.
Haploinsufficiency of cohesin protease, Separase, promotes regeneration of hematopoietic stem cells in mice
Authors: Kumar Praveen , Cheng Haizi , Paudyal Samridhdi , Nakamura Lanelle V. , Zhang Nenggang , Li Jessica T. , Sasidharan Rajkumar , Jeong Mira , Pati Debananda 
Published: January 2021

Abstract
Cohesin recently emerged as a new regulator of hematopoiesis and leukemia. In addition to cohesin, whether proteins that regulate cohesin’s function have any direct role in hematopoiesis and hematologic diseases has not been fully examined. Separase, encoded by the ESPL1 gene, is an important regulator of cohesin’s function. Canonically, protease activity of Separase resolves sister chromatid cohesion by cleaving cohesin subunit-Rad21 at the onset of anaphase. Using a Separase haploinsufficient mouse model, we have uncovered a novel role of Separase in hematopoiesis. We report that partial disruption of Separase distinctly alters the functional characteristics of hematopoietic stem/progenitor cells (HSPCs). Although analyses of peripheral blood and bone marrow of Espl1+/Hyp mice broadly displayed unperturbed hematopoietic parameters during normal hematopoiesis, further probing of the composition of early hematopoietic cells in Espl1+/Hyp bone marrow revealed a mild reduction in the frequencies of the Lin−Sca1+Kit− (LSK) or LSK CD48+CD150− multipotent hematopoietic progenitors population without a significant change in either long-term or short-term hematopoietic stem cells (HSCs) subsets at steady state. Surprisingly, however, we found that Separase haploinsufficiency promotes regeneration activity of HSCs in serial in vivo repopulation assays. In vitro colony formation assays also revealed an enhanced serial replating capacity of hematopoietic progenitors isolated from Espl1+/Hyp mice. Microarray analysis of differentially expressed genes showed that Separase haploinsufficiency in HSCs (SP-KSL) leads to enrichment of gene signatures that are upregulated in HSCs compared to committed progenitors and mature cells. Taken together, our findings demonstrate a key role of Separase in promoting hematopoietic regeneration of HSCs.
Signaling pathways essential for triple-negative breast cancer stem-like cells
Authors: Ehmsen Sidse , Ditzel Henrik J. 
Published: January 2021

Abstract
Since the discovery of breast cancer stem cells (CSCs), a significant effort has been made to identify and characterize these cells. It is a generally believe that CSCs play an important role in cancer initiation, therapy resistance, and progression of triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor prognosis. Thus, therapies targeting these cells would be a valuable addition to standard treatments that primarily target more differentiated, rapidly dividing TNBC cells. Although several cell surface and intracellular proteins have been described as biomarkers for CSCs, none of these are specific to this population of cells. Recent research is moving toward cellular signaling pathways as targets and biomarkers for CSCs. The WNT pathway, the nuclear factor-kappa B (NF-κB) pathway, and the cholesterol biosynthesis pathway have recently been identified to play a key role in proliferation, survival, and differentiation of CSCs, including those of breast cancer. In this review, we assess recent findings related to these three pathways in breast CSC, with particular focus on TNBC CSCs, and discuss how targeting these pathways, in combination with current standard of care, might prove effective and improve the prognosis of TNBC patients.
Old Is the New New: The Rhetoric of Anchoring Innovation
Authors: Sluiter Ineke 
Published: January 2021

AbstractIn life, language, and argument, we need to feel at home. “Anchoring” connects whatever seems “new” to what is considered familiar. This paper studies the argumentative use of “anchoring” in the wider context of its role in language use. “Anchoring” provides a unifying perspective in analyzing linguistic and rhetorical elements identified by different schools of thought (Sect. 2). Several features of language, elsewhere studied in the context of “discourse linguistics”, direct the addressee on how to anchor new information to the common ground. Categorizing, labeling and naming (topics from philosophy and psychology) can be considered anchoring functions. And formal linguistic iconicity anchors linguistic representations in evolutionarily older senso-motor systems. Section 3 discusses the anchoring effects of some specific discourse types: genealogy, mythology, aetiology, and etymology. All of these frequently take the form of narrative and are used in affective, “engaged” argumentation. Finally, the rhetorical and argumentative implications of the terminology of “new” and “old” itself are discussed, and one specific “anchoring trope” is analyzed, which sets up an anchor as a reference point for something new: the phrase “X is the new Y” (Sect. 4).
Strong CP violation in spin-1/2 singly charmed baryons
Authors: Ünal Y. , Meißner Ulf-G. 
Published: January 2021

Abstract
We report on the calculation of the CP-violating form factor F3 and the corresponding electric dipole moment for charmed baryons in the spin-1/2 sector generated by the QCD θ-term. We work in the framework of covariant baryon chiral perturbation theory within the extended-on-mass-shell renormalization scheme up to next-to-leading order in the chiral expansion.
A novel deletion in FLOWERING LOCUS T modulates flowering time in winter oilseed rape
Authors: Vollrath Paul , Chawla Harmeet S. , Schiessl Sarah V. , Gabur Iulian , Lee HueyTyng , Snowdon Rod J. , Obermeier Christian 
Published: January 2021

Abstract
Key message
A novel structural variant was discovered in the FLOWERING LOCUS T orthologue BnaFT.A02 by long-read sequencing. Nested association mapping in an elite winter oilseed rape population revealed that this 288 bp deletion associates with early flowering, putatively by modification of binding-sites for important flowering regulation genes.

Abstract
Perfect timing of flowering is crucial for optimal pollination and high seed yield. Extensive previous studies of flowering behavior in Brassica napus (canola, rapeseed) identified mutations in key flowering regulators which differentiate winter, semi-winter and spring ecotypes. However, because these are generally fixed in locally adapted genotypes, they have only limited relevance for fine adjustment of flowering time in elite cultivar gene pools. In crosses between ecotypes, the ecotype-specific major-effect mutations mask minor-effect loci of interest for breeding. Here, we investigated flowering time in a multiparental mapping population derived from seven elite winter oilseed rape cultivars which are fixed for major-effect mutations separating winter-type rapeseed from other ecotypes. Association mapping revealed eight genomic regions on chromosomes A02, C02 and C03 associating with fine modulation of flowering time. Long-read genomic resequencing of the seven parental lines identified seven structural variants coinciding with candidate genes for flowering time within chromosome regions associated with flowering time. Segregation patterns for these variants in the elite multiparental population and a diversity set of winter types using locus-specific assays revealed significant associations with flowering time for three deletions on chromosome A02. One of these was a previously undescribed 288 bp deletion within the second intron of FLOWERING LOCUS T on chromosome A02, emphasizing the advantage of long-read sequencing for detection of structural variants in this size range. Detailed analysis revealed the impact of this specific deletion on flowering-time modulation under extreme environments and varying day lengths in elite, winter-type oilseed rape.