bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data variability across Canadian administrative health databases: Differences in content, coding, and completeness
Authors: Doyle Carla M. , Lix Lisa M. , Hemmelgarn Brenda R. , Paterson J. Michael , Renoux Christel 
Published: September 2019

AbstractPurposeThe Canadian Network for Observational Drug Effect Studies (CNODES) is a network of Canadian research centres using administrative data to conduct distributed drug safety and effectiveness studies. In this study, we compare the provincial administrative databases and illustrate the potential impact of database differences on a CNODES study about domperidone and the risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD).MethodsWe assessed the impact of varying versions and precision of the International Classification of Diseases coding system in physician claims data, and the content and completeness of hospital discharge abstracts across CNODES sites, as these variations can introduce differences in the study cohorts formed and affect study results.ResultsIn our study of 214 962 patients, hospital diagnosis type (such as most responsible, admitting, or secondary diagnosis) was missing in some provinces, resulting in misclassification of the outcome and variation in rates and risk estimates. Incidence rates of VT/SCD ranged from 19.8 (95% confidence interval [CI] 17.7‐22.2) per 10 000 person‐years in British Columbia to 53.4 (95% CI 50.3‐56.5) in Quebec. While most provinces reported an increased risk of VT/SCD, a null effect was observed in Quebec (rate ratio 1.06; 95% CI 0.79‐1.41).ConclusionsDistributed analyses allow for rapid responses to drug safety signals. However, variation in characteristics of the administrative data across research centres can influence study results. By identifying the sources of database heterogeneity, one can evaluate the potential biases these differences may introduce, highlighting the importance of considering such variation in distributed networks.
Structural and functional analysis of the Hsp70/Hsp40 chaperone system
Authors: Liu Qinglian , Liang Ce , Zhou Lei 
Published: September 2019

AbstractAs one of the most abundant and highly conserved molecular chaperones, the 70‐kDa heat shock proteins (Hsp70s) play a key role in maintaining cellular protein homeostasis (proteostasis), one of the most fundamental tasks for every living organism. In this role, Hsp70s are inextricably linked to many human diseases, most notably cancers and neurodegenerative diseases, and are increasingly recognized as important drug targets for developing novel therapeutics for these diseases. Hsp40s are a class of essential and universal partners for Hsp70s in almost all aspects of proteostasis. Thus, Hsp70s and Hsp40s together constitute one of the most important chaperone systems across all kingdoms of life. In recent years, we have witnessed significant progress in understanding the molecular mechanism of this chaperone system through structural and functional analysis. This review will focus on this recent progress, mainly from a structural perspective.
Prediction of protein oligomer structures using GALAXY in CASP13
Authors: Baek Minkyung , Park Taeyong , Woo Hyeonuk , Seok Chaok 
Published: September 2019

AbstractMany proteins need to form oligomers to be functional, so oligomer structures provide important clues to biological roles of proteins. Prediction of oligomer structures therefore can be a useful tool in the absence of experimentally resolved structures. In this article, we describe the server and human methods that we used to predict oligomer structures in the CASP13 experiment. Performances of the methods on the 42 CASP13 oligomer targets consisting of 30 homo‐oligomers and 12 hetero‐oligomers are discussed. Our server method, Seok‐assembly, generated models with interface contact similarity measure greater than 0.2 as model 1 for 11 homo‐oligomer targets when proper templates existed in the database. Model refinement methods such as loop modeling and molecular dynamics (MD)‐based overall refinement failed to improve model qualities when target proteins have domains not covered by templates or when chains have very small interfaces. In human predictions, additional experimental data such as low‐resolution electron microscopy (EM) map were utilized. EM data could assist oligomer structure prediction by providing a global shape of the complex structure.
Population Pharmacokinetic Analysis for Imipenem–Relebactam in Healthy Volunteers and Patients With Bacterial Infections
Authors: Bhagunde Pratik , Patel Parul , Lala Mallika , Watson Kenny , Copalu William , Xu Ming , Kulkarni Pooja , Young Katherine , Rizk Matthew L. 
Published: September 2019

Relebactam is a small‐molecule β‐lactamase inhibitor developed as a fixed‐dose combination with imipenem/cilastatin. The pharmacokinetics of relebactam and imipenem across 10 clinical studies were analyzed using data from adult healthy volunteers and patients with bacterial infections. Renal function estimated by creatinine clearance significantly affected the clearance of both compounds, whereas weight and health status were of less clinical significance. Simulations were used to calculate probability of joint target attainment (ratio of free drug area under the curve from 0 to 24 hours to minimum inhibitory concentration (MIC) for relebactam and percentage of time the free drug concentration exceeded the MIC for imipenem) for the proposed imipenem/relebactam dose of 500/250 mg, with adjustments for patients with renal impairment, administered as a 30‐minute intravenous infusion four times daily. These dosing regimens provide sufficient antibacterial coverage (MIC ≤ 4 μg/mL) for all renal groups.
Consequences of regularizing the Sawyer–Eliassen equation in balance models for tropical cyclone behaviour
Authors: Wang Shanghong , Smith Roger K. 
Published: September 2019

AbstractThe consequences of regularizing the Sawyer–Eliassen equation to calculate the stream function for the axisymmetric secondary circulation of a tropical cyclone are explored. Regularization is an ad hoc procedure in which the coefficients of the equation are suitably modified to replace negative values of the discriminant by small positive values, thereby ensuring that the equation is globally elliptic. The consequences of the procedure may be understood in terms of the analogue behaviour of a stretched membrane subject to a particular force distribution. Several regularization procedures are assessed by comparing the azimuthally averaged radial flow from a three‐dimensional numerical simulation of a tropical cyclone with that from an axisymmetric balance calculation of the Sawyer–Eliassen equation, forced by diabatic and frictional terms diagnosed from the simulation. The comparison shows that the largest challenge for regularization occurs in regions of inertial instability, especially when the diagnosed forcing overlaps with such regions. In the example shown, the diagnosed balanced flow is sensitive to the particular regularization procedure and none of the procedures examined give a flow that is structurally and quantitatively close to that obtained from the numerical solution in and near the region of regularization. The flow in regions of large vertical shear that are common in the lower part of the boundary layer is less sensitive to the regularization procedure, even though such regions are ones in which there is (frictional) forcing. Nevertheless, there are comparatively large differences between the low‐level inflow in the azimuthally averaged numerical solution and the axisymmetric balance solution. These differences can be attributed to the intrinsic lack of balance in the boundary layer. This finding, together with the issues associated with regularization, is further confirmation that balance dynamics is unable to adequately capture the flow in the boundary layer, contrary to recent claims.
Math matters: mathematical knowledge plays an essential role in Chinese undergraduates' stock‐and‐flow task performance
Authors: Qi Liang , Gonzalez Cleotilde 
Published: September 2019

AbstractPeople's understanding of accumulation (stock) and of rates of change (flows) is essential to successful decision making in dynamic environments. However, past research suggests that highly educated Western people are often unable to infer the behavior of stock–flow systems. In an empirical study involving a population of university students in China, we tested whether mathematical knowledge, global–local processing and domain experience affect participants' performance in stock–flow tasks. We find that Chinese undergraduates had good performance in general, and individuals with more mathematical knowledge performed better on stock–flow tasks. We discuss the possible reasons that explain these participants' success. Future research needs to extend our work to more diverse populations across different cultures, nations and education systems. Comparative studies on the content of math education under a cross‐cultural frame are desirable to uncover more essential factors for people's understanding of stock–flow structures.© 2019 System Dynamics Society
When do investors prefer copycats? Conditions influencing the evaluation of innovative and imitative ventures
Authors: Fu Yingzhu , Tietz Matthias A. 
Published: September 2019

AbstractResearch SummaryThis article investigates the conditions under which investors preferentially evaluate fast follower business model copycats (BMCs)—less novel, imitative ventures—over novel ventures. Employing a conjoint experiment, we find that venture investors prefer fast follower BMCs when the venture team has major capability advantages in exploitation (compared to exploration). Further, we find that investors' experience reduces their preference for fast follower BMCs when the team's capability advantage is in exploitation, and reduces their preference for novel ventures when the team is strong in exploration. These findings provide important theoretical and managerial implications.Managerial SummaryBusiness model copycats represent a popular phenomenon in the global market. Fast follower BMCs are especially influential as many of them received millions of dollars of investment, and achieved billions of dollars in evaluations, both resulting in worldwide recognition. But although fast follower BMCs have the potential to conquer any market, they are not always highly valued by investors when initiating their businesses. We investigate when this is the case and find that team exploration–exploitation capabilities influence investors' evaluation preference toward novel ventures and fast follower BMCs. If entrepreneurs are skilled in exploitation, creating a fast follower BMC venture might be a great pitch to secure investment. Yet, if entrepreneurs are mostly competitive in exploration, creating fast follower BMCs does not attract investment easily.
Effects of Silver Ions on High‐Speed Electroless Copper
Authors: Wu Minxian , Xu Chao , Wang Wenchang , Wang Shiying , Mitsuzaki Naotoshi , Chen Zhidong 
Published: September 2019

AbstractFormaldehyde is one of the mostly used reductants in electroless copper. Silver ions were introduced into the plating bath to improve the plating rates and the film ductility. The linear scan voltammetry was used to study the influence of silver ions on the reduction behavior of copper, which indicates that the silver ions were co‐reduced with copper. The incorporation of silver increased copper deposition rate. The plating rate increased from 17 μm h−1 in the silver‐free solution to 29 μm h−1 as 25 mg L−1 Ag2SO4 was added. Folding tests were performed to illustrate the effect of silver on film ductility. The addition of silver ions in the plating baths improved the folding endurance of copper layers. The stability of the plating bath containing 20 mg L−1 Ag2SO4 was investigated using UV/Vis absorption spectroscopy. The bath was stable for at least 2 weeks.
Enhanced Skin Permeation of Hydrocortisone Using Nanoemulsion as Potential Vehicle
Authors: Altamimi Mohammad , Haq Nazrul , Alshehri Sultan , Qamar Wajhul , Shakeel Faiyaz 
Published: September 2019

AbstractThe current work was performed to estimate the solubility and Hansen solubility parameters of a poorly soluble corticosteroid hydrocortisone (HCN) in various components of nanoemulsion and to enhance the skin permeation rate of HCN using nanoemulsions as potential vehicles. Screening studies suggested the use of Capryol‐90 (oil), Triton‐X100 (surfactant) and Transcutol‐HP (cosurfactant) in the preparation of HCN nanoemulsions. HCN nanoemulsions were developed using low energy emulsification technique and characterized for droplet size, plolydispersity index (PDI), zeta potential (ZP), refractive index (RI), percent of transmittance (% T) and transmission electron microscopy (TEM) and evaluated for drug release behavior. Selected nanoemulsions and control (HCN suspension) were subjected to in vitro skin permeation studies. Optimized formula HSN8 showed droplet size of 52.6 nm, PDI of 0.109, ZP of −33.72 mV, RI of 1.337 and % T of 97.68%. TEM confirmed spherical‐shaped droplets in nanometer range. In vitro drug release evaluation suggested significant release of HCN from optimized nanoemulsion (98.52%) compared with control (35.85%). Skin permeation profile of HCN from optimized nanoemulsion was also significant compared with control. These results suggested the potential of nanoemulsion in enhancing the transdermal delivery of HCN via rat skin.
Does it pay to be a multinational? A large‐sample, cross‐national replication assessing the multinationality–performance relationship
Authors: Pisani Niccolò , Garcia‐Bernardo Javier , Heemskerk Eelke 
Published: September 2019

AbstractResearch SummaryDoes it pay to be a multinational? Despite decades of empirical research, we still do not know. We undertake a large‐sample, cross‐national replication of Lu and Beamish (2004) and Berry and Kaul's (2016) works to examine whether the multinationality–performance relationship is S‐shaped in a 2009–2016 panel of 889,865 firm‐year observations. Using a two‐stage least squares fixed‐effects model that accounts for endogeneity on a subsample of 32,835 multinationals from 64 countries, we find no evidence of an S‐shaped relationship; nor do we see it in any of the single‐country contexts. Our results show no evidence of any within‐firm effect of multinationality on performance, highlighting the need for more contextually‐grounded research focused on explaining between‐firm effects to advance our theoretical and empirical understanding of the multinationality‐performance relationship.Managerial SummaryWe replicate two studies that examined the relationship between a firm's multinationality and its performance. Lu and Beamish (2004) found evidence of an S‐shaped relationship—with performance first decreasing, then increasing, then decreasing again as firms expanded abroad—in a sample of Japanese firms; Berry and Kaul (2016) found no evidence of an S‐shaped pattern in a sample of U.S. multinationals. We test for the same relationship using data from nearly 250,000 firms based in over 100 countries from 2009 to 2016 and find no evidence of an S‐shaped pattern or of any effect of multinationality. Our study thus adds substantial evidence to the one shown by Berry and Kaul (2016), emphasizing the need to focus on how contextual differences influence the multinationality–performance relationship.
Investor experience and innovation performance: The mediating role of external cooperation
Authors: Boh Wai Fong , Huang Cheng‐Jen , Wu Anne 
Published: September 2019

AbstractResearch SummaryWe add to the literature examining the ownership‐innovation relationship by examining two major investor types: corporate investors and family investors. We use organizational environmental scanning as a new perspective to understand how these investors' capabilities influence firms' external cooperation and innovation performance. We found that corporate investors with broad investment experience strengthen a firm's environmental scanning, enhancing innovation performance by increasing the number of external cooperation activities the firm engages in. Conversely, family investors' broad investment experience tend to be negatively associated with the number of external cooperation and with firm innovation. Our results show that investors influence firm innovation not simply through a monitoring role but also by affecting firms' abilities to innovate, once we factor in the types of investors and their capabilities.Managerial SummaryWe investigate how two different types of investors, corporate and family, influence the innovation performance of publicly‐traded high‐tech firms in Taiwan. We found that the presence of major corporate investors with broad investment experience enhances firms' innovation performance by increasing external cooperation activities firms engage in. Corporate investors appear to enhance organizations' environmental scanning abilities and, in turn, their innovation performance. Conversely, family investors' broad investment experience is negatively associated with firm innovation because such firms engage in fewer external cooperation activities. A focus on control and social cohesion in family firms appears to decrease the emphasis on external knowledge acquisition when family investors have broad investment experience. In summary, our results show that investors' breadth of investment experience influences firms' ability to innovate.
Coupled shear‐flexural model for dynamic analysis of fixed‐base tall buildings with tuned mass dampers
Authors: Huergo Iván F. , Hernández Hugo 
Published: September 2019

SummaryAn equivalent discrete model is developed for time domain dynamic analysis of uniform high‐rise shear wall‐frame buildings with fixed base and carrying any number of tuned mass dampers (TMDs). The equivalent model consists of a flexural cantilever beam and a shear cantilever beam connected in parallel by a finite number of axially rigid members that allow the consideration of intermediate modes of lateral deformation. The proposed model was validated by a building whose lateral resisting system consists of a combination of shear walls and braced frames. The results showed the effectiveness of TMDs to reduce the peak displacements, interstory drift ratio, and accelerations when the building is subjected to a seismic load. The root mean square accelerations due to along‐wind loads also decrease if TMDs are attached to the building.
Effects of cigarette smoke components on myocardial differentiation of mouse embryonic stem cells
Authors: Kim Cho‐Won , Go Ryeo‐Eun , Ko Eul Bee , Jeung Eui‐Bae , Kim Min‐Seok , Choi Kyung‐Chul 
Published: September 2019

AbstractThe heart is the first organ formed in the developing fetus, and abnormal development of the heart is a major cause of fetal death. The adverse effects of cigarette smoke on the heart have been well established, but it is not well understood how cigarette smoke components regulate signaling molecules and cardiac specific functions during the early differentiation stage of the embryonic heart. In this study, we identified changes in the size of mouse embryoid bodies (mEBs) in response to treatment with cigarette smoke extract (CSE) via regulation of HDAC2, p53, p21, and cyclin D1 protein expression, which are cardiac differentiation and cell‐cycle markers, respectively. In addition, exposure of mouse embryonic stem cells (mESCs) to cigarette smoke components inhibited myocardial differentiation and development through the expression of HDAC1, HDAC2, GATA4, NKX2‐5, TBX5, HAND1, and Troponin I. Long‐term exposure studies showed that CSE and nicotine may delay the development of mouse cardiomyocytes from mESCs and inhibit the contractibility, which is a fundamental function of the heart. Taken together, these findings suggest that cigarette smoke components, including nicotine, may affect abnormal myocardial differentiation and development.
Incorporating local ecological knowledge to explore wolverine distribution in Alberta, Canada
Authors: Webb Shevenell M. , Anderson Robert B. , Jokinen Michael E. , Abercrombie Bill , Bildson Brian , Manzer Douglas L. 
Published: September 2019

ABSTRACTWolverines (Gulo gulo) occur at low densities in remote areas that are typically difficult to access, which has resulted in a lack of baseline data and uncertain status across parts of their range. We surveyed trappers in 2012 to gather information on local ecological knowledge of wolverine occurrence across a range of latitudes (49–59°N) in Alberta, Canada. We received questionnaires from 164 trapping areas in the Boreal Forest, Foothills, and Rocky Mountains. Similar to results from other methods of data collection, trapper observations of wolverines were associated with cooler climates and less anthropogenic disturbance. When we included data from all regions, the best model that explained recent wolverine observations included percent intact forest within the surrounding area. The odds ratio suggested that each increase of 1% in the amount of intact forest increased the odds of a trapper observing wolverine sign by 4%. In the Boreal Forest, the top model indicated that wolverines were more likely to be found in areas that had a cooler climate and more intact forest. Insights from trappers provided valuable baseline data on a sensitive species that is complementary to other research findings, and stimulated hypotheses that wolverines are linked to cooler climates and less disturbed environments. © 2019 Alberta Conservation Association. Wildlife Society Bulletin Published by Wiley Periodicals, Inc on behalf of The Wildlife Society.
TLR7 activation in epilepsy of tuberous sclerosis complex
Authors: Dombkowski Alan A. , Cukovic Daniela , Bagla Shruti , Jones McKenzie , Caruso Joseph A. , Chugani Harry T. , Chugani Diane C. 
Published: September 2019

Abstract

Background
Neuroinflammation and toll-like receptors (TLR) of the innate immune system have been implicated in epilepsy. We previously reported high levels of microRNAs miR-142-3p and miR-223-3p in epileptogenic brain tissue resected for the treatment of intractable epilepsy in children with tuberous sclerosis complex (TSC). As miR-142-3p has recently been reported to be a ligand and activator of TLR7, a detector of exogenous and endogenous single-stranded RNA, we evaluated TLR7 expression and downstream IL23A activation in surgically resected TSC brain tissue.

Methods
Gene expression analysis was performed on cortical tissue obtained from surgery of TSC children with pharmacoresistent epilepsy. Expression of TLRs 2, 4 and 7 was measured using NanoString nCounter assays. Real-time quantitative PCR was used to confirm TLR7 expression and compare TLR7 activation, indicated by IL-23A levels, to levels of miR-142-3p. Protein markers characteristic for TLR7 activation were assessed using data from our existing quantitative proteomics dataset of TSC tissue. Capillary electrophoresis Western blots were used to confirm TLR7 protein expression in a subset of samples.

Results
TLR7 transcript expression was present in all TSC specimens. The signaling competent form of TLR7 protein was detected in the membrane fraction of each sample tested. Downstream activation of TLR7 was found in epileptogenic lesions having elevated neuroinflammation indicated by clinical neuroimaging. TLR7 activity was significantly associated with tissue levels of miR-142-3p.

Conclusion
TLR7 activation by microRNAs may contribute to the neuroinflammatory cascade in epilepsy in TSC. Further characterization of this mechanism may enable the combined of use of neuroimaging and TLR7 inhibitors in a personalized approach towards the treatment of intractable epilepsy.