bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction via Functional Protein Stabilization of Hepatic Cytochromes P450 upon gp78/Autocrine Motility Factor Receptor (AMFR) Ubiquitin E3-ligase Genetic Ablation in Mice: Therapeutic and Toxicological Relevance
Authors: Kwon Doyoung , Kim Sung-Mi , Jacob Peyton , Liu Yi , Correia Maria Almira 
Published: April 2019

3.AbstractThe hepatic endoplasmic reticulum (ER)-anchored monotopic proteins, cytochromes P450 (P450s) are enzymes that metabolize endobiotics (physiologically active steroids and fatty acids) as well as xenobiotics including therapeutic/chemotherapeutic drugs, nutrients, carcinogens and toxins. Alterations of hepatic P450 content through synthesis, inactivation or proteolytic turnover influence their metabolic function. P450 proteolytic turnover occurs via ER-associated degradation (ERAD) involving ubiquitin (Ub)-dependent proteasomal degradation (UPD) as a major pathway. UPD critically involves P450 protein ubiquitination by E2/E3 Ub-ligase complexes. We have previously identified the ER-polytopic gp78/AMFR (autocrine motility factor receptor) as a relevant E3 in CYP3A4, CYP3A23 and CYP2E1 UPD. We now document that liver-conditional genetic ablation of gp78/AMFR in mice disrupts P450 ERAD, resulting in significant stabilization of Cyp2a5 and Cyps 2c, in addition to that of Cyps 3a and Cyp2e1. More importantly, we establish that such stabilization is of the functionally active P450 proteins, leading to corresponding significant enhancement of their drug metabolizing capacities. Our findings with clinically relevant therapeutic drugs (nicotine, coumarin, chlorzoxazone, and acetaminophen) and the prodrug (tamoxifen) as P450 substrates, reveal that P450 ERAD disruption could influence therapeutic drug response and/or toxicity, warranting serious consideration as a potential source of clinically significant drug-drug interactions (DDIs). Because gp78/AMFR is not only an E3 Ub-ligase, but also a cell-surface prometastatic oncogene that is upregulated in various malignant cancers, our finding that hepatic gp78/AMFR-knockout can enhance P450-dependent bioactivation of relevant cancer chemotherapeutic prodrugs is of therapeutic relevance and noteworthy in prospective drug design and development.4.Significance StatementThe cell surface and ER transmembrane protein gp78/AMFR, a receptor for the prometastatic autocrine motility factor (AMF), as well as an E3 ubiquitin-ligase involved in the ERAD of not only the tumor metastatic suppressor KAI1, but also of hepatic cytochromes P450, is upregulated in various human cancers, enhancing their invasiveness, metastatic potential and poor prognosis. Liver specific gp78/AMFR genetic ablation results in functional protein stabilization of several hepatic P450s and consequently enhanced drug and prodrug metabolism, a feature that could be therapeutically exploited in the bioactivation of chemotherapeutic prodrugs, through design and development of novel short-term gp78/AMFR chemical inhibitors.
Highly diverse fungal communities in carbon-rich aquifers of two contrasting lakes in Northeast Germany
Authors: Perkins Anita , Ganzert Lars , Rojas-Jiménez Keilor , Fonvielle Jeremy , Hose Grant C. , Grossart Hans-Peter 
Published: April 2019

AbstractFungi are an important component of microbial communities and are well known for their ability to degrade refractory, highly polymeric organic matter. In soils and aquatic systems, fungi play an important role in carbon processing, however, their diversity, community structure and function as well as ecological role, particularly in groundwater, are poorly studied. The aim of this study was to examine the fungal community composition, diversity and function of 16 groundwater boreholes located in the vicinity of two lakes in NE Germany that are characterized by contrasting trophic status. The analysis of 28S rRNA gene sequences amplified from the groundwater revealed high fungal diversity and clear differences in community structure between both aquifers. Most sequences were assigned toAscomycotaandBasidiomycota, but members ofChytridiomycota, Cryptomycota, Zygomycota, Blastocladiomycota, GlomeromycotaandNeocallmastigomycotawere also detected. In addition, 27 species of fungi were successfully isolated from the groundwater wells and tested for their ability to degrade complex organic polymers – the predominant carbon source in the wells. Most isolates showed positive activities for at least one of the tested polymer types, with three strains, belonging to the generaGibberella, IsariaandCadophora, being able to degrade all tested substrates. Our results highlight the high diversity of fungi in groundwater, and point to their important ecological role in breaking down highly polymeric organic matter in these isolated microbial habitats.
His bundle has shorter chronaxie than adjacent ventricular myocardium: Implications for pacemaker programming
Authors: Jastrzębski Marek , Moskal Paweł , Bednarek Agnieszka , Kiełbasa Grzegorz , Vijayaraman Pugazhendhi , Czarnecka Danuta 
Published: April 2019

AbstractBackgroundStrength-duration curves for permanent His bundle (HB) pacing are potentially important for pacemaker programming.ObjectiveWe aimed to calculate strength-duration curve and chronaxie of the His bundle (HB) and of the adjacent right ventricular (RV) working myocardium and to analyze zones of selective HB capture and battery current drain when pacing at different pulse durations (PDs).MethodsConsecutive patients with permanent HB pacing were studied. The RV and HB capture thresholds were assessed at several PDs. Battery current drain and zones of selective HB capture at PDs of 0.1, 0.2, 0.4 and 1.0 ms were determined.ResultsIn the whole group (n =127) the HB chronaxie was shorter than the RV chronaxie. This difference was driven by patients with selective HB pacing (HB chronaxie of 0.47 vs RV chronaxie of 0.79 ms). Strength-duration curve for HB had lower rheobase and its steep portion started at shorter PDs thus creating wider distance - zone of programmable selective HB pacing - between the HB and RV strength-duration curves at shorter PDs. The battery current drain was lower with pacing at PDs of 0.1 - 0.4 ms vs 1.0 ms. Chronaxie adjusted PDs offered lowest current drain.ConclusionFor the first time the strength-duration curves for permanent selective and non-selective HB pacing were determined. Selective HB capture and battery longevity can be promoted by shorter PDs (0.2 ms). Longer PDs (1.0 ms) offer bigger safety margin for RV capture and may be preferable if simultaneous RV capture during HB pacing is desired.
Biofilm of Klebsiella pneumoniae minimize phagocytosis and cytokine expression by macrophage cell line
Authors: Rathore Sudarshan Singh , Cheepurupalli Lalitha , Gangwar Jaya , Raman Thiagarajan , Ramakrishnan Jayapradha 
Published: April 2019

AbstractInfectious bacteria in biofilm mode are involved in many of persistent infections. Owing to its importance in clinical settings many in vitro and in vivo studies have analysed the structural and functional properties of biofilm, its resistance to antibiotic exposure etc. Currently the immune mechanism toward the clearance of biofilm infections is being investigated. K. pneumoniae is one of the major leading causes of biofilm infections on indwelling medical devices. There was no previous literature that demonstrates the interactions of macrophage cells lines and Klebsiella biofilm, as the first report, we investigated the in vitro response of Klebsiella biofilm to phagocytosis and cytokine expression. We developed an in vitro model to study the interactions of Kebsiella biofilm and macrophage. The phagocytosis assay was performed for heat inactivated and live biofilm. A similar phagocytic response against both biofilms were observed when these cells were exposed to RAW 264.7 macrophages. Also, the expressions of TLR2, iNOS, inflammatory cytokines such as IL-β1, IFN-γ, IL-6, IL-12, IL-4, TNF-α and anti-inflammatory cytokines, IL-10 during phagocytosis were analysed. These results collectively demonstrated that the rate of phagocytosis was an average of 15% for both biofilms. Also, when activated macrophage was exposed to heat-inactivated or live biofilms, there was a significant increase in proinflammatory cytokine genes together with expected increase in TLR2 and iNOS. Thus, it is clear that macrophage response against biofilm producing K. pneumoniae results in increase in phagocytic rate and a corresponding increase in inflammatory cytokine gene expression which could be important for clearing K. pneumoniae cells.
Preparation and optimization of MEPEG-PLGA nanoparticles for gene delivery
Authors: Monash Leah , Smith John 
Published: April 2019

AbstractThis paper demonstrates a method to prepare a cationic methoxy-terminated polyethylene glycol-polylactic acid polyglycolic acid block polymer (MePEG-PLGA) nanoparticle by a nanoparticle precipitation method was established. This study used single factor design and orthogonal experiment to select the optimal experimental scheme and examined the physical properties of the nanoparticles such as surface morphology, particle size distribution, zeta potential, DNA binding rate, and DNA protection ability. Results indicate that the optimal size of the prepared nanoparticles was 89.7 nm and the surface potential was 28.3 mV. The nanoparticles were scattered under transmission electron microscope, the size was uniform, the surface was smooth, and the distribution was spherical. The DNA binding rate was 80.2 %, and can well protect the contained genes from nuclease degradation. Conclusion The cationic nanoparticles prepared by nanoparticle precipitation method are expected to be highly efficient gene carriers. The preparation of cationic methoxy-terminated polyethylene glycol-polylactic acid polyglycolic acid block polymer (MePEG-PLGA) by nanoparticle precipitation method. Nanoparticle method. Method This study used single factor design and orthogonal experiment to select the optimal experimental scheme, and examined the physical properties of the nanoparticles such as surface morphology, particle size distribution, Zeta potential, DNA binding rate, and DNA protection ability. Results The optimal size of the prepared nanoparticles was 89.7 nm and the surface potential was 28.3 mV. The nanoparticles were scattered under transmission electron microscope, the size was uniform, the surface was smooth, and the distribution was spherical. The DNA binding rate was 80.2 %, and can well protect the contained genes from nuclease degradation. Conclusion The cationic nanoparticles prepared by nanoparticle precipitation are expected to be efficient gene carriers.
Big data analysis on the business process and management for the store layout and bundling sales
Authors: Liao Shu-hsien , Tasi Yi-Shan 
Published: April 2019

Purpose
In the retailing industry, database is the time and place where a retail transaction is completed. E-business processes are increasingly adopting databases that can obtain in-depth customers and sales knowledge with the big data analysis. The specific big data analysis on a database system allows a retailer designing and implementing business process management (BPM) to maximize profits, minimize costs and satisfy customers on a business model. Thus, the research of big data analysis on the BPM in the retailing is a critical issue. The paper aims to discuss this issue.

Design/methodology/approach
This paper develops a database, ER model, and uses cluster analysis, C&R tree and the a priori algorithm as approaches to illustrate big data analysis/data mining results for generating business intelligence and process management, which then obtain customer knowledge from the case firm’s database system.

Findings
Big data analysis/data mining results such as customer profiles, product/brand display classifications and product/brand sales associations can be used to propose alternatives to the case firm for store layout and bundling sales business process and management development.

Originality/value
This research paper is an example to develop the BPM of database model and big data/data mining based on insights from big data analysis applications for store layout and bundling sales in the retailing industry.
Analytical calculation of magnetic field in surface-mounted permanent-magnet machines with air-gap eccentricity
Authors: Faiz Jawad , Hassanzadeh Mohammadreza , Kiyoumarsi Arash 
Published: April 2019

Purpose
This paper aims to present an analytical method, which combines the complex permeance (CP) and the superposition concept, to predict the air-gap magnetic field distribution in surface-mounted permanent-magnet (SMPM) machines with eccentric air-gap.

Design/methodology/approach
The superposition concept is used twice; first, to predict the magnetic field distribution in slot-less machine with eccentric air-gap, the machine is divided into a number of sections. Then, for each section, an equivalent air-gap length is determined, and the magnetic field distribution is predicted as a concentric machine model. The air-gap field in the slot-less machine with eccentricity can be combined from these concentric models. Second, the superposition concept is used to find the CP under eccentricity fault. At this end, the original machine is divided into a number of sections which may be different from the one for slot-less magnetic field prediction, and for each section, the CP is obtained by equivalent air-gap length of that section. Finally, the air-gap magnetic field distribution is predicted by multiplying the slot-less magnetic field distribution and the obtained CP.

Findings
The radial and tangential components of the air-gap magnetic flux density are obtained using the proposed method analytically. The finite element analysis is used to validate the proposed method results, showing good agreements with the analytical results.

Originality/value
This paper addresses the eccentricity fault impact upon the air-gap magnetic field distribution of SMPM machines. This is done by a combined analysis of the complex permeance (CP) method and the superposition concept. This contrasts to previous studies which have instead focused on the subdomain method.
FE analysis of coupled electromagnetic-thermal phenomena in the squirrel cage motor working at high ambient temperature
Authors: Baranski Mariusz 
Published: April 2019

Purpose
This paper aims to elaborate the method and algorithm for the analysis of the influence of high temperature on electric and thermal properties of the materials, as well as thermal phenomena process.

Design/methodology/approach
The paper presents specially author’s software for the transient finite element analysis of coupled electromagnetic-thermal problems in a squirrel cage induction motor. The numerical implementation is based on finite element method and step-by-step algorithm. The nonlinearity of a magnetic circuit, the dependence of electric and thermal parameters on temperature, the movement of a rotor and skewed rotor bars have been taken into account. To verify the developed algorithm and software, the influence of high ambient temperature on selected electromagnetic and thermal parameters of the induction motor was examined.

Findings
The results of simulations compared with measurements confirm the adequacy of this approach to the analysis of coupled electromagnetic-thermal problems.

Research limitations/implications
3D effects have only been taken into account when using quasi-3D techniques (e.g. the multi-slice for skewed rotor slots).

Practical implications
The author’s software developed can be useful in the analysis and design of squirrel cage motors, especially motors working in high ambient temperature.

Originality/value
The paper offers appropriate author’s software for the transient and steady-state analysis of coupled electromagnetic and thermal problems in squirrel cage motors with skewed slots.
Understanding real estate investments through big data goggles
Authors: Cajias Marcelo 
Published: April 2019

Purpose
This paper aims to develop a conceptual understanding and a methodological approach for calculating residential net initial yields for both a buy-to-hold and rental investment strategy from hedonic models.

Design/methodology/approach
The markets modelled comprehend of dwellings for rent and sell in Germany. For each of them, two regression models are estimated to extract implicit prices and rents for an artificial identical dwelling and estimate the willingness to pay for the same asset from both a buy-to-hold and rental investment strategy.

Findings
The 3,381 estimated net initial yields in the 161 German markets showed a spatial pattern with the biggest and most attractive cities showing the lowest yields and a self-adjusting process in the markets surrounding the top cities. The net initial yields over time show that prices have increased stronger than rents, leading to rock bottom yields for residential assets and a significant premium in comparison to government bond yields. The approach responds to the spatial hierarchy of markets in Germany, meaning that the level of the estimated yields is accurate and achievable from an investment perspective.

Practical implications
The investment case in residential markets is certainly unique as net initial yields are scarce, especially due to the relatively low number of investment comparables. The paper sheds light on this problem from a conceptual and methodological perspective and confirms that investment yields are deducible by making usage of hedonic models and big data.

Originality/value
In the era of digitalization and big data, residential assets are mostly brought to the market via digital multiple listing systems. Transparency is an essential barrier when assessing the pricing conditions of markets and deriving investment decisions. Although international brokers do provide detailed investment comparables on – mostly commercial – real estate markets, the residential sector remains a puzzle when it comes to investment yields. The paper sheds light on this problem.
Bank earnings management using commission and fee income
Authors: Ozili Peterson K. , Outa Erick 
Published: April 2019

Purpose
The purpose of this paper is to investigate whether banks use commission and fee (CF) income to manage reported earnings as an income-increasing or income smoothing strategy.

Design/methodology/approach
The authors employ the regression methodology to detect real earnings management.

Findings
The authors find that banks use CF income for income smoothing purposes and this behaviour persists during recessionary periods and in environments with stronger investor protection. The implication of the findings is that bank non-interest income which achieves diversification gains to banks is also used to manipulate reported earnings.

Research limitations/implications
The findings show that real earnings management is prevalent among banks in Africa. Further research into earnings management should examine real earnings management among non-financial firms in developing regions.

Practical implications
From an accounting standard setting perspective, the evidence suggests the need for national/international standard setters to adopt strict revenue recognition rules that ensure that banks or firms report the actual fees they make, and to discourage banks from delaying (or deferring) the collection of fee income to manage or smooth reported earnings opportunistically.

Originality/value
This study contributes to the positive accounting theory (PAT) literature which examines the accounting and non-accounting decisions that influence managers’ choice of accounting methods in financial reporting. Extending the PAT, the authors show that certain conditions can incentivize managers to engage in earning management such as during recessions and weak institutional quality or weak investor protection.
Analyst coverage and future stock price crash risk
Authors: He Guanming , Bai Lu , Ren Helen Mengbing 
Published: April 2019

PurposeWhether financial analysts play an effective role as information intermediaries and monitors has triggered a wide spread of debate among academics and practitioners to date. The purpose of this paper is to complement this debate by investigating the association between analyst coverage and firm-specific future stock price crash risk.Design/methodology/approachRegression analysis is based on a large sample of US public firms and the crash risk measure of Huttonet al.(2009). Potential endogeneity concerns are alleviated by restricting the sample period to the post-Regulation-FD period and conducting an analysis of the impact threshold for a confounding variable method per Larcker and Rusticus (2010).FindingsEvidence reveals that a high level of analyst coverage is associated with lower future stock price crash risk. Furthermore, the negative association between analyst coverage and stock price crash risk is stronger for firms that have high financial opacity. Additionally, analyst forecast pessimism is negatively associated with future crash risk.Research limitations/implicationsOur research provides evidence in support for the view that financial analysts play an active information intermediary role in a way that increases information transparency of a firm and reduces its crash risk. Also, our study offers support for the view that analysts perform an effective monitoring role in a way that constraints management’s bad news hoarding activities and reduces future crash risk.Practical implicationsThis study is of interest to investors who seek analyst reports for their investment decision making and for information providers who demand external financing. The findings of this study also have some other important implications for practitioners, given the economic and welfare consequences of stock price crashes.Originality/valueThis study offers support for the view that analysts serve positive roles as information intermediaries and monitors in the US stock market.