bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blocking 17β‐hydroxysteroid dehydrogenase type 1 in endometrial cancer: a potential novel endocrine therapeutic approach
Authors: Konings Gonda FJ , Cornel Karlijn MC , Xanthoulea Sofia , Delvoux Bert , Skowron Margaretha A , Kooreman Loes , Koskimies Pasi , Krakstad Camilla , Salvesen Helga B , van Kuijk Kim , Schrooders Yannick JM , Vooijs Marc , Groot Arjan J , Bongers Marlies Y , Kruitwagen Roy FPM ,   ENITEC, Romano Andrea 
Published: November 2017

AbstractThe enzyme type 1 17β‐hydroxysteroid dehydrogenase (17β‐HSD‐1), responsible for generating active 17β‐estradiol (E2) from low‐active estrone (E1), is overexpressed in endometrial cancer (EC), thus implicating an increased intra‐tissue generation of E2 in this estrogen‐dependent condition. In this study, we explored the possibility of inhibiting 17β‐HSD‐1 and impairing the generation of E2 from E1 in EC using in vitro, in vivo, and ex vivo models. We generated EC cell lines derived from the well‐differentiated endometrial adenocarcinoma Ishikawa cell line and expressing levels of 17β‐HSD‐1 similar to human tissues. In these cells, HPLC analysis showed that 17β‐HSD‐1 activity could be blocked by a specific 17β‐HSD‐1 inhibitor. In vitro, E1 administration elicited colony formation similar to E2, and this was impaired by 17β‐HSD‐1 inhibition. In vivo, tumors grafted on the chicken chorioallantoic membrane (CAM) demonstrated that E1 upregulated the expression of the estrogen responsive cyclin A similar to E2, which was impaired by 17β‐HSD‐1 inhibition. Neither in vitro nor in vivo effects of E1 were observed using 17β‐HSD‐1‐negative cells (negative control). Using a patient cohort of 52 primary ECs, we demonstrated the presence of 17β‐HSD‐1 enzyme activity (ex vivo in tumor tissues, as measured by HPLC), which was inhibited by over 90% in more than 45% of ECs using the 17β‐HSD‐1 inhibitor. Since drug treatment is generally indicated for metastatic/recurrent and not primary tumor, we next demonstrated the mRNA expression of the potential drug target, 17β‐HSD‐1, in metastatic lesions using a second cohort of 37 EC patients. In conclusion, 17β‐HSD‐1 inhibition efficiently blocks the generation of E2 from E1 using various EC models. Further preclinical investigations and 17β‐HSD‐1 inhibitor development to make candidate compounds suitable for the first human studies are awaited. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Genetic landscape of papillary thyroid carcinoma in the Chinese population
Authors: Liang Jialong , Cai Wanshi , Feng Dongdong , Teng Huajing , Mao Fengbiao , Jiang Yi , Hu Shanshan , Li Xianfeng , Zhang Yujie , Liu Baoguo , Sun Zhong Sheng 
Published: November 2017

AbstractImprovement in the clinical outcome of human cancers requires characterization of the genetic alterations underlying their pathogenesis. Large‐scale genomic and transcriptomic characterization of papillary thyroid carcinomas (PTCs) in Western populations has revealed multiple oncogenic drivers which are essential for understanding pathogenic mechanisms of this disease, while, so far, the genetic landscape in Chinese patients with PTC remains uncharacterized. Here, we conducted a large‐scale genetic analysis of PTCs from patients in China to determine the mutational landscape of this cancer. By performing targeted DNA amplicon and targeted RNA deep‐sequencing, we elucidated the landscape of somatic genetic alterations in 355 Chinese patients with PTC. A total of 88.7% of PTCs were found to harbor at least one candidate oncogenic driver genetic alteration. Among them, around 72.4% of the cases carried BRAF mutations; 2.8% of cases harbored RAS mutations; and 13.8% of cases were characterized with in‐frame gene fusions, including seven newly identified kinase gene fusions. TERT promoter mutations were likely to occur in a sub‐clonal manner in our PTC cohort. The prevalence of somatic genetic alterations in PTC was significantly different between our Chinese cohort and TCGA datasets for American patients. Additionally, combined analyses of genetic alterations and clinicopathologic features demonstrated that kinase gene fusion was associated with younger age at diagnosis, larger tumor size, and lymph node metastasis in PTC. With the analyses of DNA rearrangement sites of RET gene fusions in PTC, signatures of chromosome translocations related to RET fusion events were also depicted. Collectively, our results provide fundamental insight into the pathogenesis of PTC in the Chinese population. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
An algorithm to detect unexpected increases in frequency of reports of adverse events in EudraVigilance
Authors: Pinheiro Luis C. , Candore Gianmario , Zaccaria Cosimo , Slattery Jim , Arlett Peter 
Published: November 2017

AbstractPurposeThe European Medicines Agency developed an algorithm to detect unexpected increases in frequency of reports, to enhance the ability to detect adverse events that manifest as increases in frequency, in particular quality defects, medication errors, and cases of abuse or misuse.MethodsAn algorithm based on a negative binomial time‐series regression model run on 6 sequential observations prior to the monitored period was developed to forecast monthly counts of reports. A heuristic model to capture increases in counts when the previous 4 observations were null supplemented the regression. Count data were determined at drug‐event combination. Sensitivity analyses were run to determine the effect of different methods of pooling or stratifying count data. Positive retrospective detections and positive predictive values (PPVs) were determined.ResultsThe algorithm detected 8 of the 13 historical concerns, including all concerns of quality defects. The highest PPV (1.29%) resulted from increasing the lower count threshold from 3 to 5 and including literature reports in the counts. Both the regression model and the heuristic model components to the algorithm contributed to the detection of concerns. Sensitivity analysis indicates that stratification by commercial product reduces the PPV but suggests that pooling counts of related events may improve it.ConclusionThe results are encouraging and suggest that the algorithm could be useful for the detection of concerns that manifest as changes in frequency of reporting; however, further testing, including in prospective use, is warranted.
Semi‐transparent plastic solar cell based on oxide‐metal‐oxide multilayer electrodes
Authors: Lim Dong Chan , Jeong Jae Hoon , Hong Kihyon , Nho Sungho , Lee Joo‐Yul , Hoang Quoc Viet , Lee Sang Kyu , Pyo Kyunglim , Lee Dongil , Cho Shinuk 
Published: November 2017

AbstractSemi‐transparent plastic solar cells are currently highly attractive for their potential as the most prominent components for building‐integrated photovoltaics. However, the power conversion efficiency (PCE) of semi‐transparent plastic solar cells still lags behind due to the lack of a suitable transparent top electrode which can be easily fabricated. Here, we demonstrate high performance semi‐transparent plastic solar cells by introducing an oxide‐metal‐oxide (OMO) multilayer composed of MoO3 and Ag as a transparent top electrode. Because the conductivity of the OMO electrode is governed by an intermediate Ag layer sandwiched between 2 MoO3 layers, the PCE also strongly depends on the thickness of the intermediate Ag layer in the OMO electrode. By controlling the thickness of Ag layer, we obtained various PCE values from 4.5% with ~50% maximum transparency in the visible region to 9.1% with ~5% maximum transparency in the visible region. In addition, in order to get closer to practical application, 2 sizes of mini‐module devices were fabricated on a larger (10.0 cm × 10.0 cm) substrate for outdoor operation and small‐sized (7.0 cm × 5.0 cm) substrates for indoor operation were demonstrated using 3 materials of different color.
Ab initio quantum chemical calculation of electron density, electrostatic potential, and electric field of biomolecule based on fragment molecular orbital method
Authors: Ishikawa Takeshi 
Published: November 2017

AbstractEfficient quantum chemical calculations of electrostatic properties, namely, the electron density (EDN), electrostatic potential (ESP), and electric field (EFL), were performed using the fragment molecular orbital (FMO) method. The numerical errors associated with the FMO scheme were examined at the HF, MP2, and RI‐MP2 levels of theory using 4 small peptides. As a result, the FMO errors in the EDN, ESP, and EFL were significantly smaller than the magnitude of the electron correlation effects, which indicated that the FMO method provides sufficiently accurate values of electrostatic properties. In addition, an attempt to reduce the computational effort was proposed by combining the FMO scheme and a point charge approximation. The error due to this approximation was examined using 2 proteins, prion protein and human immunodeficiency virus type 1 protease. As illustrative examples, the ESP values at the molecular surface of these proteins were calculated at the MP2 level of theory.
New theoretical insight on the acid sites distribution, their local structures and acid strength of the SAPO‐11 molecular sieve
Authors: Sierraalta Anibal , Añez Rafael , Coll David S. , Alejos Paola 
Published: November 2017

AbstractONIOM(DFT:PM3) calculations were carried out to investigate and characterize possible acid sites of SAPO‐11 molecular sieve. Two functionals were employed: B3LYP and ωB97X‐D. This last functional includes dispersion effects that are absent in the former. Benzene, pyridine, and ammonia interaction energies as well as the OH stretching frequencies of the POH, SiOH, and bridged Si(OH)Al groups were used to characterize the acid sites. This work shows that the adsorption of benzene on the surface is as strong as the adsorptions inside main channel of SAPO‐11. Pyridine adsorption on the surface is weaker than the one corresponding to the main channel. NH3molecule interacts strongly with all OH groups or acid sites present in SAPO‐11. Moreover, the results reveal that it is possible to adsorb two NH3molecules at only one Brønsted site. The adsorption of the second NH3molecule is energetically favorable mainly due to the hydrogen bond formation between the NH3molecules. In general the interaction energy increases with the type of functional used, according to the trend ωB97X‐D > B3LYP. The results show that ONIOM methodology seems to be suited to investigate the acid sites in SAPO‐11.
Regional Differences between the Rate of Change of CO2 Emission Intensity of Chinese Provinces and Implications for Sustainable Development
Authors: Li Hong , Hu Jianbo , Zhang Wei 
Published: November 2017

AbstractThis paper constructs an efficiency model of carbon emission reduction (ECER), and uses provincial panel data from 1995 to 2014 to examine the factors influencing ECER at province level in China. Results show that TA (technical advancement) and SE (scale effect) dominate ECER, but their effects vary across regions. TE (technical efficiency) has the potential to enhance ECER, given the increased TA in the three studied regions. The negative effect of IS (industry structure) on ECER in the West (the western region) is heavier than that in the central region and the East, while the East (the eastern region) has a lower negative effect of ES (energy structure) on ECER than the central region and the West. To increase the efficiency of emission reduction policies, the central and local governments should consider these regionally heterogeneous factors. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Bridging practice and process research to study transient manifestations of strategy
Authors: Mirabeau Laurent , Maguire Steve , Hardy Cynthia 
Published: November 2017

Research Summary: At the intersection of Strategy Process (SP) and Strategy‐as‐Practice (SAP) research lies the focal phenomenon they share—strategy, which manifests itself in a variety of ways: intended, realized, deliberate, emergent, unrealized, and ephemeral strategy. We present a methodology comprised of three stages that, when integrated in the manner we suggest, permit a rich operationalization and tracking of strategy content for all manifestations. We illustrate the utility of our methodology for bridging SP and SAP research by theorizing practices that are more likely to give rise to unrealized and ephemeral strategy, identifying their likely consequences, and presenting a research agenda for studying these transient manifestations.Managerial Summary: Managers know well that, sometimes for good reasons and other times with negative consequences for organizations, not all aspects of strategic plans are implemented with fidelity, resulting in unrealized strategy; and not all bottom‐up projects receive the middle‐management support they need to become realized, resulting in ephemeral strategy making. Surprisingly, however, these transient manifestations of strategy receive little attention in the scholarly literature. Our paper addresses this gap by presenting a methodology for tracking all six manifestations of strategy (intended, realized, deliberate, emergent, unrealized, and ephemeral strategy), highlighting the interdependent relations among them. It also describes strategy making practices that are likely to give rise to the two transient manifestations, i.e., unrealized and ephemeral strategy, as well as their consequences for subsequent strategy making.
Database engines: Evolution of greenness
Authors: Miranskyy A. V. , Al‐zanbouri Z. , Godwin D. , Bener A. B. 
Published: November 2017

AbstractInformation technology consumes up to 10% of the world's electricity generation, contributing to CO2 emissions and high energy costs. Data centers, particularly databases, use up to 23% of this energy. Therefore, building an energy‐efficient (green) database engine could reduce energy consumption and CO2 emissions. The goal of this study is to understand the factors driving databases' energy consumption and execution time throughout their evolution. We conducted an empirical case study of energy consumption by 2 MySQL database engines, InnoDB and MyISAM, across 40 releases. We examined the relationships of 4 software metrics to energy consumption and execution time to determine which metrics reflect the greenness and performance of a database. Our analysis shows that database engines' energy consumption and execution time increase as databases evolve. Moreover, the lines of code (LOC) metric is correlated moderately to strongly with energy consumption and execution time in 88% of cases. Our findings provide insights to practitioners and researchers. Database administrators may use them to select a fast, green release of the MySQL database engine. MySQL developers may use LOC to assess products' greenness and performance. Researchers may use our findings to further develop new hypotheses or build models predicting greenness and performance of databases.
Melatonin improves survival and respiratory activity of yeast cells challenged by alpha‐synuclein and menadione
Authors: Zampol Mariana A. , Barros Mario H. 
Published: November 2017

AbstractOne of the hallmarks of Parkinson disease is α‐synuclein aggregate deposition that leads to endoplasmic reticulum stress, Golgi fragmentation and impaired energy metabolism with consequent redox imbalance. In the last decade, many studies have used Saccharomyces cerevisiae as a model in order to explore the intracellular consequences of α‐synuclein overexpression. In this study we propose to evaluate the respiratory outcome of yeast cells expressing α‐synuclein. Cell viability or growth on selective media for respiratory activity was mainly affected in the α‐synuclein‐expressing cells if they were also treated with menadione, which stimulates reactive oxygen species production. We also tested whether melatonin, a natural antioxidant, would counteract the deleterious effects of α‐synuclein and menadione. In fact, melatonin addition improved the respiratory growth of α‐synuclein/menadione‐challenged cells, presented a general improvement in the enzymatic activity of the respiratory complexes and finally elevated the rate of mitophagy, an important cellular process necessary for the clearance of damaged mitochondria. Altogether, our data confirms that α‐synuclein impairs respiration in yeast, which can be rescued by melatonin addition.
Influence of phosphatidylserine and phosphatidylethanolamine on farnesol tolerance in Candida albicans
Authors: Hasim Sahar , Vaughn Elyse N. , Donohoe Dallas , Gordon Donna M. , Pfiffner Susan , Reynolds Todd B. 
Published: November 2017

AbstractCandida albicans is among the most common human fungal pathogens. The ability to undergo the morphological transition from yeast to hyphal growth is critical for its pathogenesis. Farnesol, a precursor in the isoprenoid/sterol pathway, is a quorum‐sensing molecule produced by C. albicans that inhibits hyphal growth in this polymorphic fungus. Interestingly, C. albicans can tolerate farnesol concentrations that are toxic to other fungi. We hypothesized that changes in phospholipid composition are one of the factors contributing to farnesol tolerance in C. albicans. In this study, we found that loss of enzymes that synthesize the phospholipids phosphatidylserine (PS) and/or phosphatidylethanolamine (PE) compromise the tolerance of C. albicans to farnesol. Compared with wild type, the phospholipid mutant cho1∆/∆ (loss of PS and decreased PE synthesis) shows greater inhibition of growth, loss of ATP production, increased consumption of oxygen, and increased formation of reactive oxygen species in the presence of farnesol. The cho1∆/∆ mutant also exhibits decreased sensitivity to mitochondrial ATPase inhibition, suggesting that cells lacking PS and/or downstream PE rely less on mitochondrial function for ATP synthesis. These data reveal that PS and PE play roles in farnesol tolerance and maintaining mitochondrial respiratory function.
Map-based cloning of the fertility restoration locus Rfm1 in cultivated barley (Hordeum vulgare)
Authors: Rizzolatti Carine , Bury Paul , Tatara Edouard , Pin Pierre A. , Rodde Nathalie , Bergès Hélène , Budar Françoise , Mireau Hakim , Gielen Jan J. L. 
Published: November 2017

AbstractHybridization technology has proven valuable in enhancing yields in many crops, but was only recently adopted in the small grain cereals. Hybrid varieties in barley (Hordeum vulgare) rely on the cytoplasmic male sterility (CMS) system msm1 derived from Hordeum vulgare ssp. spontaneum. The major restorer gene described for the msm1 system is known as Rfm1 and maps to the top of chromosome 6H. To gain further insight into mechanisms underlying male fertility restoration in barley, we used a map-based cloning approach to identify the nuclear gene involved in the restoration mechanism of this hybridization system. Taking advantage of the available genomic resources in barley in combination with a custom-made non-gridded BAC library developed from a restorer line, we cloned and sequenced the Rfm1 restorer locus. The characterization and annotation of the nucleotide sequence for the Rfm1 restorer allele allowed for the identification of the candidate gene for Rfm1. The Rfm1 locus carries a tandem repeat of a gene encoding a pentatricopeptide repeat (PPR) protein. Surprisingly, Rfm1 belongs to the PLS-DYW subfamily of PPR genes known for their involvement in RNA editing in plants organelles, but that to date have not been identified as restorer genes.
Prevalence of Genetic Disorders and GLUT1 Deficiency in a Ketogenic Diet Clinic
Authors: Hewson Stacy , Brunga Ledia , Ojeda Matilde Fernandez , Imhof Elizabeth , Patel Jaina , Zak Maria , Donner Elizabeth J. , Kobayashi Jeff , Salomons Gajja S. , Mercimek-Andrews Saadet 
Published: November 2017

AbstractBetween July of 2012 and December of 2014, 39 patients were enrolled prospectively to investigate the prevalence of glucose transporter 1 (GLUT1) deficiency in a ketogenic diet clinic. None of them had GLUT1 deficiency. All patients seen in the same clinic within the same period were reviewed retrospectively. A total of 18 of these 85 patients had a genetic diagnosis, including GLUT1 deficiency, pathogenic copy number variants, congenital disorder of glycosylation, neuronal ceroid lipofuscinosis type II, mitochondrial disorders, tuberous sclerosis, lissencephaly, and SCN1A-, SCN8A-, and STXBP1-associated epileptic encephalopathies. The prevalence of genetic diagnoses was 21% and prevalence of GLUT1 deficiency was 2.4% in our retrospective cohort study.
Explorer la structure interne des constructions causatives du français
Authors: Hu Xiaoshi 
Published: November 2017

RésuméLe présent article porte sur la structure interne des constructions causatives du français. Son argumentation se base sur deux idées essentielles : que l'interprétation derespectivementrévélerait l'effet d'intervention dans les constructions bi-propositionnelles, et que la montée du quantifieur serait soumise à la minimalité et à la Condition d'impénétrabilité des phases. J'utiliserai ces deux phénomènes comme tests pour justifier d'une part la relation morpho-syntaxique entre le verbe causatiffaireet le verbe causativisé, et d'autre part la dérivation de l'ordre VOS (verbe-objet-sujet) du complément defaire. Je compte démontrer que les constructions causatives du français sont analogues aux constructions ECM (Exceptional Case Marking), qui impliquent un TP défectif enchâssé; et que l'ordre VOS du complément defaire, dans la constructionfaire-àet dans la constructionfaire-par, impliquent deux dérivations différentes. Le premier est dérivé parObject Shift, tandis que le deuxième est dérivé parSmuggling.
Modeling the mechanical properties of ultra-thin polymer films
Authors: Espinosa-Loza Francisco , Stadermann Michael , Aracne-Ruddle Chantel , Casey Rebecca , Miller Philip , Whitesides Russel 
Published: November 2017

A modeling method to extract the mechanical properties of ultra-thin films (10–100 nm thick) from experimental data generated by indentation of freestanding circular films using a spherical indenter is presented. The relationship between the mechanical properties of the film and experimental parameters including load, and deflection are discussed in the context of a constitutive material model, test variables, and analytical approaches. Elastic and plastic regimes are identified by comparison of finite element simulation and experimental data.