bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of affinity capillary electrophoresis for charge heterogeneity profiling of biopharmaceuticals
Authors: Hutanu Andrei , Kiessig Steffen , Bathke Andrea , Ketterer Rolf , Riner Sonja , Olaf Stracke Jan , Wild Markus , Moritz Bernd 
Published: September 2019

AbstractCharge heterogeneity profiling is important for the quality control (QC) of biopharmaceuticals. Because of the increasing complexity of these therapeutic entities [1], the development of alternative analytical techniques is needed. In this work, flow‐through partial‐filling affinity capillary electrophoresis (FTPFACE) has been established as a method for the analysis of a mixture of two similar monoclonal antibodies (mAbs). The addition of a specific ligand results in the complexation of one mAb in the co‐formulation, thus changing its migration time in the electric field. This allows the characterization of the charged variants of the non‐shifted mAb without interferences. Adsorption of proteins to the inner capillary wall has been circumvented by rinsing with guanidine hydrochloride before each injection. The presented FTPFACE approach requires only very small amounts of ligands and provides complete comparability with a standard CZE of a single mAb.
Influence of cyclic wetting‐drying on the mechanical strength characteristics of coal samples: A laboratory‐scale study
Authors: Chen Shaojie , Jiang Tianqi , Wang Huaiyuan , Feng Fan , Yin Dawei , Li Xiushan 
Published: September 2019

AbstractWater‐coal interactions have gained much recent attention, although few studies focus on the strength of coal under wetting‐drying cycles. This study investigates changes in the microstructure and mechanical strength of coal that are induced by water‐coal interactions, at the macroscale and microscale. Fourteen specimens after continuous wetting and fourteen specimens after wetting‐drying cycles were tested, indicating that peak stress and elastic modulus decrease with increasing continuous wetting time and number of wetting‐drying cycles, while peak strain increases. We analyzed changes in the coal microstructure using a scanning electron microscope (SEM) and the Image Pro Plus 6.0 (IPP 6.0) software. The regression model for cyclic wetting‐drying reveals that porosity and pore circularity are the main correlation indicators associated with uniaxial compressive strength. Therefore, different numbers of wetting‐drying cycles could induce different degrees of damage to coal, which increases progressively through gradual changes to its microstructure. These findings indicate that wetting‐drying cycles have a more significant impact on the stability of coal mass than continuous wetting. Our results are of use in determining the size of coal pillars, and expanding the knowledge base related to the mechanical properties of coal mass, water bursting, water recharge channels, and the stress‐crack‐permeability evolution law in mines.
Maternal Transfer of Persistent Organic Pollutants to Sea Turtle Eggs: A Meta-Analysis Addressing Knowledge and Data Gaps Toward an Improved Synthesis of Research Outputs
Authors: Muñoz Cynthia C. , Vermeiren Peter 
Published: September 2019

Abstract
Maternal transfer of persistent organic pollutants (POPs) confronts developing embryos with a pollution legacy and poses conservation concerns due to its potential impacts unto subsequent generations. We conducted a systematic review focusing on: 1) processes of POP maternal transfer, 2) challenges and opportunities to synthesizing current knowledge on POP concentrations in eggs, and 3) a meta-analysis of patterns in current egg pollution data. Results suggest selective maternal transfer of individual compounds. These relate to biological factors such as the foraging and remigration behavior, and to the selective mobilization of POPs during vitellogenesis, such as increased diffusion limitation for lipophilic POPs and slower release and higher reabsorption of apolar POPs. A key gap relates to knowledge of further selective toxicokinetics during embryonic development, as research to date has mainly focused on initial uptake into eggs. Challenges in the synthesis of current data on egg contamination profiles relate to methodological differences, varying analytical approaches, restricted data access, and reporting transparency among studies. To increase opportunities in the use of current data, we propose best practice guidelines, and synthesize a database on POP concentrations within sea turtle eggs. The meta-analysis revealed a geographical and taxonomic bias on the West Atlantic Ocean, including the Gulf of Mexico and Caribbean Sea, with most studies conducted on green turtles. Concentrations of POPs show temporal patterns related to trends in usage, production, release, and persistence in the environment, often with regional patterns. The trophic level has the potential to influence POP patterns with higher concentrations in loggerheads compared to other species, but this is confounded by temporal and geographic trends. We argue for more mechanistically process-focused and methodologically comparable research. Environ Toxicol Chem 2019;39:9–29. © 2019 SETAC
Characterization of juice fermented with Lactobacillus plantarum EM and its cholesterol‐lowering effects on rats fed a high‐fat and high‐cholesterol diet
Authors: Jeon Yu Bin , Lee Jae‐Joon , Chang Hae Choon 
Published: September 2019

AbstractThe aim of this study was to investigate the ability of Lactobacillus plantarum EM as a starter culture to control cabbage–apple juice fermentation and to explore the cholesterol‐lowering effects of the fermented juice (EM juice) in rats. L. plantarum EM produced strong antimicrobial activities against bacteria and fungi, suppressing other microorganisms in the fermented juice, and was the dominant organism during fermentation and storage. The EM juice also showed strong and broad‐spectrum antimicrobial activity. Rats fed a high‐fat and high‐cholesterol diet and administered EM juice showed significantly reduced total cholesterol (TC), triglyceride, and LDL‐cholesterol levels, as well as a reduced atherogenic index, lower cardiac factors in serum, and lower TC levels in the liver, while total lipid and TC levels in the rat feces increased. Reverse transcription–polymerase chain reaction analysis revealed that the hepatic mRNA expression of HMG‐CoA reductase decreased and the expressions of cholesterol 7α‐hydroxylase and low‐density lipoprotein receptor increased in rats administered EM juice. The effects of EM juice on rats included inhibition of cholesterol synthesis as well as enhancement of cholesterol uptake and cholesterol excretion. The results of this study indicate that the use of L. plantarum EM as a functional starter culture for juice fermentation exerts microbial control, enhances sanitary safety, and provides beneficial food effects against hypercholesterolemia.
Up‐regulation of miR‐let7a‐5p Leads to Decreased Expression of ABCC2 in Obstructive Cholestasis
Authors: Balasubramaniyan Natarajan , Devereaux Michael W. , Orlicky David J. , Sokol Ronald J. , Suchy Frederick J. 
Published: September 2019

Adenosine triphosphate–binding cassette subfamily C member 2 (ABCC2/Abcc2) is critically important to biliary excretion of many endobiotic and xenobiotic compounds, and is a major driving force for bile acid–independent bile flow. Abcc2 expression is reduced at the messenger RNA (mRNA) and protein levels in various forms of experimental cholestasis. In a microRNA (miRNA) screen of mouse liver after biliary obstruction, we found that miRNA let7a‐5p was significantly up‐regulated approximately 4‐fold. Similarly, ABCC2 mRNA was depleted and miRNA let7a‐5p was elevated over 4‐fold in livers of children with biliary atresia compared with normal livers. In silico analysis predicted that let7a‐5p would target the 3′ untranslated region (3′ UTR) of ABCC2/Abcc2 RNA. The objective of this study was to determine whether let7a‐5p contributes to the depletion of ABCC2/Abcc2 in cholestasis. To demonstrate the functional importance of miRNA let7a‐5p in regulating the expression of ABCC2, co‐transfection of a let7a‐5p mimic and an ABCC2‐3′ UTR luciferase construct into Huh‐7 cells led to a marked inhibition of luciferase activity by about 60%‐70% compared with controls, which was reversed by a let7a‐5p mimic inhibitor. Expression of this mimic led to a significant decrease in endogenous ABCC2 mRNA and protein levels in a Huh‐7 liver cell line, which could be blocked by expression of a let7a‐5p mimic inhibitor. Injection of a lentivirus let7a‐5p inhibitor into normal mouse liver or into mouse liver after common bile duct ligation led to a significant increase in endogenous Abcc2 mRNA and protein levels and a depletion of let7a‐5p mRNA levels compared with untreated, saline‐injected livers or livers treated with an inactive lentivirus control. Conclusion: These studies demonstrate that miR‐let7a‐5p is involved in regulating ABCC2/Abcc2 expression, and is aberrantly up‐regulated in obstructive cholestasis.
Metabolic syndrome affects the long‐term survival of patients with non‐endometrioid carcinoma of the uterine corpus
Authors: Shou Huafeng , Yan Kangzhen , Song Jia , Zhao Lingqin , Zhang Yingli , Ni Juan 
Published: September 2019

AbstractObjectiveTo probe the influence of metabolic syndrome (MS) on the long‐term survival of patients with non‐endometrioid adenocarcinoma.MethodsBetween January 2003 and December 2012, 139 Chinese patients with non‐endometrial adenocarcinoma were analyzed in a retrospective study. Patients who had received any treatment before surgery were excluded. Survival times were compared between patients with and without MS.ResultsOverall, 41 (29.5%) patients had MS; the highest incidence of MS was observed in those with uterine serous carcinoma (19/45, 42.2%). For uterine serous carcinoma or adenosquamous carcinoma, MS was an independent predictive factor of morbidity (P=0.023 and 0.016, respectively). For the overall population, those with MS had a significantly lower survival rate than those without MS (P=0.008), and the median overall survival (mOS) was 15 months versus 55 months (P<0.001, hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.29–0.69). Similarly, a lower survival rate (P=0.020) and shorter mOS (19 months vs 55 months, P=0.007, HR 0.41, 95% CI 0.20–0.83) were also found in the uterine serous carcinoma population with MS. Multivariate Cox regression analyses showed that disease stage (P=0.023) and MS (P=0.008) were independent prognostic factors for uterine serous carcinoma.ConclusionThe present study suggests that MS is a prognostic factor for non‐endometrioid adenocarcinoma, especially uterine serous carcinoma.
Use of SysML for the creation of FMEAs for Reliability, Safety, and Cybersecurity for Critical Infrastructure
Authors: Hecht Myron , Baum David 
Published: September 2019

AbstractA method for producing a Failure Modes and Effects Analysis (FMEA) from SysML is presented together with a simple critical infrastructure system example. The significance of the method is the modeling of failure propagation which enables not only an automated approach but significant additional analysis results that can be used to support reliability, safety, and cybersecurity. The analysis products from a tool implementing this method together with the insight and analytical benefits they provide are discussed.
Usage of Digital Twin Technologies during System Modeling and Testing in Vessel Traffic Services System Project
Authors: ÜZÜMCÜ Serdar , MERT Abdullah Aykut , ATAY Fatih 
Published: September 2019

AbstractDesign and Integration of a Vessel Traffic Services (VTS) System with the implementation of a newly VTS software is a highly complex project with some challenges on interfaces and timing. The involvement of directives of command operation center personal and information from shipleader as stakeholder as well as different systems as automatic identification system, radar systems, electro optical systems, physical security systems beside the traffic services system makes is difficult manage the overall system design. A system of systems approach with MBSE techniques and usage of tools as designing with digital twin technology helps to simplify overviewing system design and checking interface definitions on the left side of the Vee model before implementation and integration process starts. A software intensive system with involvement of electrical and mechanical engineering including structural engineering for measurement of tolerances of sensors installed on towers gives an opportunistic theme for digital twin modeling of devices.
Inclusion of human values in the specification of systems: bridging design and systems engineering
Authors: Pinto José , Falk Kristin , Kjørstad Marianne 
Published: September 2019

AbstractThis paper investigates a method for ensuring that systems engineers generate requirements related to human values. It looks at the work of a project team that designs and develops complex systems in a company recognized for the application of Systems Engineering to deliver innovative systems. The research data was drawn from a real project. We developed a tool that prescribes a structure to analyze human stakeholders and to describe use case scenarios. The tool enabled the systems engineers to generate twenty‐five new requirements all of which were added to the system specification. Thirteen of these requirements contain aspects related to human values. Initially, the specification included only two requirements related to human values. We conclude that the importance of specifying human values has increased among the engineers of the team. Further investigation is ongoing in order to evaluate the potential of generalizing the new tool, its efficiency and effectiveness.
An SSM‐TRIZ Methodology for Business Problem Structuring
Authors: Phillips Ibukun , Kenley C. Robert 
Published: September 2019

AbstractCheckland developed Soft Systems Methodology (SSM) to address problem situations from a systems perspective; however, SSM needs to be extended with other methods to find superior solutions that overcome the need for a compromise or trade‐off between conflicting or contradictory elements. This paper extends Checkland's SSM approach to resolve problems with conflicting or contradictory elements. This work integrates the powerful benefits of TRIZ‐based analysis into SSM and provides a means for systemic resolution of business problems with conflicting sub‐system elements. This paper acknowledges that soft problems can have conflicting relationships among their elements, compares the strengths and weaknesses of SSM and TRIZ in problem structuring, and presents a collaborative SSM‐TRIZ approach for problem structuring. Finally, this paper applies the joint methodology to examine the business problem of developing a Professional Development platform for INCOSE. Although SSM‐TRIZ helps structure problems with opposing requirements, it does not always provide definitive, prescriptive solution implementations for technical and business issues. Hence, hard thinking approaches cannot be discarded in practice after implementing SSM‐TRIZ.
A strategic asset planning decision analysis: An integrated System Dynamics and multi‐criteria decision‐making method
Authors: Elsawah Sondoss , Danesh Darius , Ryan Michael 
Published: September 2019

AbstractAsset planning is a complex and dynamic problem, where the decision maker is often faced with the challenge of making decisions now about aspects that will change over the asset lifetime. This paper is a part of an ongoing study whose goal is to develop decision‐support methods and tools (qualitative and quantitative) to support asset planning. In this context, this paper's objective is to demonstrate an integrated approach for combining System Dynamics (SD) and Multi‐criteria Decision‐Making (MCDM). To support the design approach, the paper uses a multi‐method design framework, from the wider Operations Research/Management Science (OR/MS) literature, as a theoretical lens to review and synthesize literature. To apply and test this approach in practice, the paper uses as a test case the classic asset replacement problem from the asset management literature. The test case is applied in a real‐life decision support project for fleet planning in a military organization. Results showcase the value of using SD (qualitative and quantitative) methods and MCDM, both independently and integrated, to support asset planning.
Augmenting requirements with models to improve the articulation between system engineering levels and optimize V&V practices
Authors: Bonnet Stephane , Voirin Jean-Luc , Navas Juan 
Published: September 2019

AbstractModel‐based systems engineering has developed significantly over the last few years, resulting in an increased usage of models in systems specification and architecture description. The question of the positioning of requirement engineering versus MBSE is a recurrent one. This paper describes one vision of this articulation where textual and model requirements actually complete each other. The results are improved contracts across engineering levels and more formalized verification and validation practices.
Toxic effects of triptolide on adrenal steroidogenesis in H295R cells and female rats
Authors: Xu Ling‐Yan , Wu Wei , Cheng Rui , Sun Li‐Xin , Jiang Zhen‐Zhou , Zhang Lu‐Yong , Zhang Zun‐Jian , Su Yu‐Wen , Huang Xin 
Published: September 2019

AbstractTriptolide (TP), a major active ingredient of Tripterygium wilfordii, exerts potent immunosuppressive effects in the treatment of rheumatoid arthritis but is not widely used in clinical practice due to its multiorgan toxicity, particularly hepatotoxicity, nephrotoxicity, and reproductive toxicity. An LC‐MS/MS approach was employed to explore the endocrine‐disrupting effects of TP. The endocrine‐disrupting effects of various concentrations (0‐100 nM) of TP for 48 hour were firstly investigated using an in vitro model (H295R cell line). It was found that TP did not decrease cell viability. The transcriptional levels of steroidogenic enzymes in H295R cells were assessed by quantificational real‐time polymerase chain reaction. The possible adrenal and endocrine effects of oral administration of TP (0, 50, and 500 μg/kg) for 28 days on both normal and collagen‐induced arthritis (CIA) rats were also explored. The serum and adrenal tissue hormone levels (corticosterone and progesterone) and adrenal histopathology were analyzed, with the results that TP significantly decreased the level of cortisol in H295R cells and the level of plasma corticosterone in both normal and CIA rats. Histological alterations in adrenal cortex were observed at the dose of 500 μg/kg. Exposure to TP for 48 hour had an obvious inhibitory effect on the messenger RNA transcript levels of HSD3B2, CYP21A2, CYP17A1, and CYP11B1, which is essential for the synthesis of corticosteroids. In a word, TP leads to the disorder of corticosteroid synthesis and secretion, and corticosteroid may be a potential biomarker for the treatment of multiorgan toxicity of TP.
Revising the definition of vertical margin involvement following endoscopic polypectomy may reduce unnecessary surgery in patients with malignant colorectal polyps
Authors: Richards Colin , Kumarasinghe Priyanthi , Hessamodini Hannah , Waldron Alice , Fernando Diharah , Hodder Rupert , Jacques Angela , Raftopoulos Spiro 
Published: September 2019

Background and Study AimsEndoscopically resected malignant colorectal polyps (MCPs) present a dilemma regarding whether the risk of residual disease justifies a major bowel resection. Overtreatment is common, and the vast majority of patients who undergo resection have no residual tumor. The aim of this study was to investigate whether revising the definition of vertical margin involvement following MCP polypectomy could reduce unnecessary surgery.Patients and MethodsThis was a cohort study of consecutive patients with MCPs treated at a tertiary hospital between 2004 and 2018. Data on demographics, index colonoscopy, polyp pathology, and any subsequent surgical resection were analyzed. Polypectomy resection margins were reviewed and measured to the nearest decimal place. The ability of existing guidelines (requiring a margin clearance of ≥ 1 mm) to predict residual disease was compared to a revised version requiring a margin clearance of ≥ 0.1 mm.ResultsA total of 129 patients with an MCP were included. Of these 129 patients, 77 (60%) underwent surgical resection, of which 62 (81%) had no residual tumor. Existing guidelines, requiring a margin clearance of ≥ 1 mm, classified 28 patients as being at “low risk” for residual disease. Of these, four underwent surgery, but none had residual tumor (P = 0.031). Revised guidelines, requiring a margin clearance of ≥ 0.1 mm, classified 44 patients as “low risk.” Of these, in the 13 that had surgery, no residual tumor was found (P = 0.003).ConclusionsRevising the definition of vertical margin involvement leads to more patients being correctly classified as being at low risk of residual disease. This has the potential to reduce unnecessary surgery in patients with MCPs.
Consumers' choice among peer‐to‐peer sharing platforms: The other side of the coin
Authors: Stofberg Nicole , Bridoux Flore 
Published: September 2019

AbstractMany peer‐to‐peer sharing platforms are transforming their business model from sharing for free to renting with or without in‐person interactions. How will these changes affect consumers’ participation in peer‐to‐peer sharing of personal items? The work studies consumers’ choice among three business models that vary on two dimensions: “free versus renting” and “with or without in‐person interactions.” The novelty is to consider that consumers’ choice can be driven by their perceptions of relationships among peers, which are shaped by the business models of sharing platforms. Perceptions of communal sharing (CS) relationships among peers are found to differ across business models and to predict consumers’ choice among the platforms above and beyond the economic and social benefits that consumers seek. Interestingly, perceptions of CS are not only found to explain the choice of a sharing for the free business model over the two others, but also the choice of renting with in‐person interactions over renting without in‐person interactions. For managers of peer‐to‐peer sharing platforms, this means that renting does not make sharing completely similar to traditional market exchanges as long as in‐person interactions are involved. For scholars, this calls for more work on the factors that bring about perceptions of CS.