bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Glutathione/Metallothionein System Challenges the Design of Efficient O2‐Activating Copper Complexes
Authors: Santoro Alice , Calvo Jenifer S. , Peris‐Díaz Manuel David , Krężel Artur , Meloni Gabriele , Faller Peter 
Published: February 2020

AbstractCopper complexes are of medicinal and biological interest, including as anticancer drugs designed to cleave intracellular biomolecules by O2 activation. To exhibit such activity, the copper complex must be redox active and resistant to dissociation. Metallothioneins (MTs) and glutathione (GSH) are abundant in the cytosol and nucleus. Because they are thiol‐rich reducing molecules with high CuI affinity, they are potential competitors for a copper ion bound in a copper drug. Herein, we report the investigation of a panel of CuI/CuII complexes often used as drugs, with diverse coordination chemistries and redox potentials. We evaluated their catalytic activity in ascorbate oxidation based on redox cycling between CuI and CuII, as well as their resistance to dissociation or inactivation under cytosolically relevant concentrations of GSH and MT. O2‐activating CuI/CuII complexes for cytosolic/nuclear targets are generally not stable against the GSH/MT system, which creates a challenge for their future design.
Reprogramming of sugar transport pathways in Escherichia coli using a permeabilized SecY protein‐translocation channel
Authors: Guo Qiang , Mei Sen , Xie Chong , Mi Hao , Jiang Yang , Zhang Shi‐Ding , Tan Tian‐Wei , Fan Li‐Hai 
Published: February 2020

AbstractIn the initial step of sugar metabolism, sugar‐specific transporters play a decisive role in the passage of sugars through plasma membranes into cytoplasm. The SecY complex (SecYEG) in bacteria forms a membrane channel responsible for protein translocation. The present work shows that permeabilized SecY channels can be used as nonspecific sugar transporters in Escherichia coli. SecY with the plug domain deleted allowed the passage of glucose, fructose, mannose, xylose, and arabinose, and, with additional pore‐ring mutations, facilitated lactose transport, indicating that sugar passage via permeabilized SecY was independent of sugar stereospecificity. The engineered E. coli showed rapid growth on a wide spectrum of monosaccharides and benefited from the elimination of transport saturation, improvement in sugar tolerance, reduction in competitive inhibition, and prevention of carbon catabolite repression, which are usually encountered with native sugar uptake systems. The SecY channel is widespread in prokaryotes, so other bacteria may also be engineered to utilize this system for sugar uptake. The SecY channel thus provides a unique sugar passageway for future development of robust cell factories for biotechnological applications.
The product‐market performance benefits of environmental policy: Why customer awareness and firm innovativeness matter
Authors: Rahman Mahabubur , Aziz Saqib , Hughes Mathew 
Published: February 2020

AbstractResearchers have widely studied the nexus between corporate environmental (“green”) policy and its green performance and firm financial performance, but with mixed findings. A potential explanation for these mixed findings is the focus of extant studies on the direct and immediate impact of environmental performance on financial performance to the exclusion of firm‐specific boundary conditions. Furthermore, all prior research study the effect of environmental performance on either stock market‐based performance measures (i.e., stock return) or accounting‐based performance measures (i.e., return on assets). A missing third dimension of firm performance, product–market‐based performance (i.e., market share), has so far remained unexplored despite representing a crucial objective when innovating. Using Newsweek's annual green ranking as a novel measure of environmental performance for a panel of U.S. firms from 2010 to 2015, this paper attempts to fill these voids in the literature. The results show a positive relationship between firms' environmental performance and market share as a measure of product–market‐based performance. The findings further demonstrate that this relationship is positively moderated by the level of customer awareness and innovativeness of the firm: The higher the level of awareness of a firm's environmental credentials and innovativeness, the stronger the effects of environmental performance on market share. Our results are robust against endogeneity concerns and alternative measures of firm financial and environmental performance.
Dynamic surveillance of tamoxifen‐resistance in ER‐positive breast cancer by CAIX‐targeted ultrasound imaging
Authors: Li Ying , Chen Xiaoyu , Zhou ZhiWei , Li Qing , Westover Kenneth D. , Wang Meng , Liu Junjun , Zhang Sheng , Zhang Jin , Xu Bo , Wei Xi 
Published: February 2020

AbstractTamoxifen‐based hormone therapy is central for the treatment of estrogen receptor positive (ER+) breast cancer. However, the acquired tamoxifen resistance, typically co‐exists with hypoxia, remains a major challenge. We aimed to develop a non‐invasive, targeted ultrasound imaging approach to dynamically monitory of tamoxifen resistance. After we assessed acquired tamoxifen resistance in 235 breast cancer patients and a list of breast cancer cell lines, we developed poly(lactic‐co‐glycolic acid)‐poly(ethylene glycol)‐carbonic anhydrase IX mono antibody nanobubbles (PLGA‐PEG‐mAbCAIX NBs) to detect hypoxic breast cancer cells upon exposure of tamoxifen in nude mice. We demonstrate that carbonic anhydrase IX (CAIX) expression is associated with breast cancer local recurrence and tamoxifen resistance both in clinical and cellular models. We find that CAIX overexpression increases tamoxifen tolerance in MCF‐7 cells and predicts early tamoxifen resistance along with an oscillating pattern in intracellular ATP level in vitro. PLGA‐PEG‐mAbCAIX NBs are able to dynamically detect tamoxifen‐induced hypoxia and tamoxifen resistance in vivo. CAIX‐conjugated NBs with noninvasive ultrasound imaging is powerful for dynamically monitoring hypoxic microenvironment in ER+ breast cancer with tamoxifen resistance.
Mechanistic Insights into the Regio‐ and Stereoselectivities of Testosterone and Dihydrotestosterone Hydroxylation Catalyzed by CYP3A4 and CYP19A1
Authors: Li Junhao , Tang Yun , Li Weihua , Tu Yaoquan 
Published: February 2020

AbstractThe hydroxylation of nonreactive C−H bonds can be easily catalyzed by a variety of metalloenzymes, especially cytochrome P450s (P450s). The mechanism of P450 mediated hydroxylation has been intensively studied, both experimentally and theoretically. However, understanding the regio‐ and stereoselectivities of substrates hydroxylated by P450s remains a great challenge. Herein, we use a multi‐scale modeling approach to investigate the selectivity of testosterone (TES) and dihydrotestosterone (DHT) hydroxylation catalyzed by two important P450s, CYP3A4 and CYP19A1. For CYP3A4, two distinct binding modes for TES/DHT were predicted by dockings and molecular dynamics simulations, in which the experimentally identified sites of metabolism of TES/DHT can access to the catalytic center. The regio‐ and stereoselectivities of TES/DHT hydroxylation were further evaluated by quantum mechanical and ONIOM calculations. For CYP19A1, we found that sites 1β, 2β and 19 can access the catalytic center, with the intrinsic reactivity 2β>1β>19. However, our ONIOM calculations indicate that the hydroxylation is favored at site 19 for both TES and DHT, which is consistent with the experiments and reflects the importance of the catalytic environment in determining the selectivity. Our study unravels the mechanism underlying the selectivity of TES/DHT hydroxylation mediated by CYP3A4 and CYP19A1 and is helpful for understanding the selectivity of other substrates that are hydroxylated by P450s.
Interlaboratory concordance of p16/Ki‐67 dual‐staining interpretation in HPV‐positive women in a screening population
Authors: Benevolo Maria , Mancuso Pamela , Allia Elena , Gustinucci Daniela , Bulletti Simonetta , Cesarini Elena , Carozzi Francesca Maria , Confortini Massimo , Bisanzi Simonetta , Carlinfante Gabriele , Rubino Teresa , Rollo Francesca , Marchi Natalina , Farruggio Angelo , Pusiol Teresa , Venturelli Francesco , Giorgi Rossi Paolo ,   the New Technologies for Cervical Cancer 2 Working Group
Published: February 2020

Backgroundp16/Ki‐67 dual staining is a candidate biomarker for triaging human papillomavirus (HPV)–positive women. Reproducibility is needed for adopting a test for screening. This study assessed interlaboratory reproducibility in HPV‐positive women.MethodsAll women positive for HPV from the Italian New Technologies for Cervical Cancer 2 study, were included in this study. ThinPrep slides were immunostained for p16/Ki‐67 in 4 laboratories and were interpreted in 7 laboratories. Each slide had 3 reports from different laboratories. Slides were classified as valuable or inadequate, and valuable slides were classified as positive (at least 1 double‐stained cell) or negative. Interlaboratory reproducibility was evaluated with κ values.ResultsOverall, we obtained 9300 reports for 3100 cases; 905 reports (9.7%) were inadequate. The overall adequacy concordance was poor (κ = 0.224; 95% confidence interval [CI], 0.183‐0.263). The overall positivity concordance was moderate (κ = 0.583; 95% CI, 0.556‐0.610). Of the 176 cervical intraepithelial neoplasia 2+ (CIN‐2+) lesions found in HPV DNA–positive women, 158 had a valid result: 107 were positive in all 3 reports (sensitivity for CIN‐2+, 67.7%; 95% CI, 59.8%‐74.9%), 23 were positive in 2 reports (sensitivity of the majority report, 82.3%; 95% CI, 75.4%‐87.9%), and 15 were positive in 1 report (sensitivity of at least 1 positive result, 91.8%; 95% CI, 86.3%‐95.5%). Thirteen CIN‐2+ cases were negative in all 3 reports. The overall positivity concordance in CIN‐2+ samples was κ = 0.487 (95% CI, 0.429‐0.534), whereas in the non–CIN‐2+ samples, it was κ = 0.558 (95% CI, 0.528‐0.588).ConclusionsThe p16/Ki‐67 assay showed poor reproducibility for adequacy and good reproducibility for positivity comparable to that of cervical cytology. Nevertheless, the low reproducibility does not affect the sensitivity for CIN‐2+.
Parallel computing modes of multiobjective game
Authors: Bao Wei , Pan Chuang Ye , Wang Lu , Zhang Qing , Xie Neng Gang 
Published: February 2020

SummaryFor the design of multiobjective optimum decision, three methods based on parallel computing and game theory were raised to transfer the multiobjective design into the decision. Then, the multiobjective optimum design problems of numerical calculation examples, compensative sheave block, and antiseismic design of arch structures can be solved. Three parallel computing modes (ie, I, II, and III) were designed correspondingly. First, parallel mode I can make the game process visually intuitive with the disadvantage that the computing load cannot be balanced. Second, parallel mode II can better solve the imbalance of computing load between different objectives, obtain good parallel speedup and host efficiency. Furthermore, parallel mode III has the advantages of the above two parallel modes. However, its disadvantage is that data exchange between computing units is frequent, and this results in an increase in communication time. The simulation results suggest that all the parallel game algorithms can give considerations to multiple objectives, improve the seeking efficiency and make the solutions more robust.
Measuring life satisfaction among psychiatric patients: Measurement invariance and validity of the Satisfaction with Life Scale
Authors: Jovanović Veljko , Lazić Milica , Gavrilov‐Jerković Vesna 
Published: February 2020

AbstractThe main aim of the present study was to evaluate the measurement invariance and the convergent validity of the Satisfaction with Life Scale (SWLS) across clinical and nonclinical samples. A total of 216 psychiatric patients (47.7% females; Mage = 44.56) and 235 participants from the general population (54.5% females; Mage = 43.11 years) were recruited. The measurement invariance was tested by a multi‐group confirmatory factor analysis. Full scalar invariance of the SWLS was supported. Psychiatric patients reported substantially lower life satisfaction than participants from the general population. The SWLS demonstrated good convergent validity in both samples. The present study supported the use of the SWLS as a measure of life satisfaction among psychiatric patients.
Both glycaemic control and insulin dose during pregnancy in women with type 1 diabetes are associated with neonatal anthropometric measures and placental weight
Authors: García‐Patterson Apolonia , Ovejero Diana , Miñambres Inka , Chico Ana , Gil Pedro Alejandro , Martínez María‐José , Adelantado Juan María , de Leiva Alberto , Gich Ignasi , Desoye Gernot , de Mouzon Sylvie Hauguel , Corcoy Rosa 
Published: February 2020

AbstractBackgroundTo investigate longitudinal associations of maternal glucose/HbA1c and insulin dose with birthweight‐related outcomes in women with type 1 diabetes.MethodsWe performed a cohort study including 473 pregnant women with type 1 diabetes with singleton pregnancies. We investigated maternal self‐monitored blood glucose (SMBG, mmol/L), HbA1c (%, mmol/mol) and insulin dose (IU/kg/day) in the three trimesters as potential independent variables, while adjusting for potential confounders. Outcomes of interest were birthweight, birthweight SD score, neonatal length, weight/length index, ponderal index and placental weight. Multiple linear regression analysis was performed with separate analyses for SMBG and HbA1c.ResultsMaternal glucose and insulin dose were independently associated with birthweight‐related outcomes. In the main analysis, in the first trimester most associations were positive for insulin dose, in the second the associations were positive for glucose and inverse for insulin while in the third there were no associations. Most sensitivity analyses produced consistent results. In a sensitivity analysis splitting the first trimester in two periods, positive associations of maternal insulin with birthweight‐related outcomes were observed in weeks 0+ to 6+.ConclusionsEarly in pregnancy in women with type 1 diabetes, maternal insulin dose is positively associated with birthweight‐related outcomes, whereas in the second trimester, a positive association with SMBG emerges and the association with maternal insulin becomes inverse. If confirmed in other cohorts, these results would have implications in the management of women with type 1 diabetes.
Degradation and longevity of solar photovoltaic modules—An analysis of recent field studies in Ghana
Authors: Quansah David A. , Adaramola Muyiwa S. , Takyi Gabriel 
Published: February 2020

AbstractSolar photovoltaic (PV) technology has attracted an enormous amount of attention and investment in recent years—translating to record deployment levels. This is due to in part to its potential role as a cleaner energy source in the emissions‐constrained development agenda that is currently being pursued at both global and national levels. Solar PV has also been propelled to the forefront of today's menu of technological options by virtue of its attributes such as scalability, fast deployment lead times, and low operating cost. Substantial investments are needed in the coming years in order to accomplish climate targets and other goals set by various countries and regional/subregional blocs. In support of informed investment decision‐making and ultimately, improved outcomes of solar PV projects, there has been an uptick in studies on operational performance of fielded PV systems across the globe. These studies are, however, geographically unbalanced, and there is the need for data from underrepresented regions. This paper presents a synthesis of results obtained from recent seminal field studies on PV module performance degradation in Ghana. The studies altogether analyzed sixty‐five (65) modules (mono‐ and polycrystalline silicon) from twenty‐nine (29) installations across the country (1118 module‐years). The field‐aged modules were characterized in situ using current‐voltage (I‐V) curves, visual inspection checklists, and thermal imaging. Annual module performance degradation rates (peak power) of 0.8%‐7%, 0.55%‐2.07%, and 1.1%‐2.4% were found for modules located in various climate subcategorizations.
Gas‐kinetic unified algorithm for plane external force‐driven flows covering all flow regimes by modeling of Boltzmann equation
Authors: Li Zhi‐Hui , Hu Wen‐Qiang , Peng Ao‐Ping , Wu Jun‐Lin , Lee Chun‐Hian 
Published: February 2020

SummaryThe nonequilibrium steady gas flows under the external forces are essentially associated with some extremely complicated nonlinear dynamics, due to the acceleration or deceleration effects of the external forces on the gas molecules by the velocity distribution function. In this article, the gas‐kinetic unified algorithm (GKUA) for rarefied transition to continuum flows under external forces is developed by solving the unified Boltzmann model equation. The computable modeling of the Boltzmann equation with the external force terms is presented at the first time by introducing the gas molecular collision relaxing parameter and the local equilibrium distribution function integrated in the unified expression with the flow state controlling parameter, including the macroscopic flow variables, the gas viscosity transport coefficient, the thermodynamic effect, the molecular power law, and molecular models, covering a full spectrum of flow regimes. The conservative discrete velocity ordinate (DVO) method is utilized to transform the governing equation into the hyperbolic conservation forms at each of the DVO points. The corresponding numerical schemes are constructed, especially the forward‐backward MacCormack predictor‐corrector method for the convection term in the molecular velocity space, which is unlike the original type. Some typical numerical examples are conducted to test the present new algorithm. The results obtained by the relevant direct simulation Monte Carlo method, Euler/Navier‐Stokes solver, unified gas‐kinetic scheme, and moment methods are compared with the numerical analysis solutions of the present GKUA, which are in good agreement, demonstrating the high accuracy of the present algorithm. Besides, some anomalous features in these flows are observed and analyzed in detail. The numerical experience indicates that the present GKUA can provide potential applications for the simulations of the nonequilibrium external‐force driven flows, such as the gravity, the electric force, and the Lorentz force fields covering all flow regimes.
How Youth and Adults With Negative Reading Histories Found a Way to Enjoy Reading
Authors: Hall Leigh A. 
Published: February 2020

AbstractIndividuals who self‐identify as poor readers can have a range of reading experiences, practices, and abilities. The author examined how adolescents and adults who self‐identified as poor readers (a) found enjoyment in reading an interactive fiction app, (b) why they chose to engage with a text‐based app, and (c) if their involvement with the app changed their reading practices. Participants were heavily involved in reading on the app, and their experiences allowed them to enjoy reading and begin to see themselves as readers in a positive light. However, all participants reported that they were uninterested in reading outside the app. Findings indicate that a positive experience can help youth and adults change how they engage with texts, but more support is required to help them engage with texts more broadly.
PDK1 is important lipid kinase for RANKL‐induced osteoclast formation and function via the regulation of the Akt‐GSK3β‐NFATc1 signaling cascade
Authors: Xiao Dongliang , Zhou Quan , Gao Yunbing , Cao Baichuan , Zhang Qiong , Zeng Gaofeng , Zong Shaohui 
Published: February 2020

AbstractPerturbations in the balanced process of osteoblast‐mediated bone formation and osteoclast‐mediated bone resorption leading to excessive osteoclast formation and/or activity is the cause of many pathological bone conditions such as osteoporosis. The osteoclast is the only cell in the body capable of resorbing and degrading the mineralized bone matrix. Osteoclast formation from monocytic precursors is governed by the actions of two key cytokines macrophage‐colony‐stimulating factor and receptor activator of nuclear factor‐κB ligand (RANKL). Binding of RANKL binding to receptor RANK initiates a series of downstream signaling responses leading to monocytic cell differentiation and fusion, and subsequent mature osteoclast bone resorption and survival. The phosphoinositide‐3‐kinase (PI3K)‐protein kinase B (Akt) signaling cascade is one such pathway activated in response to RANKL. The 3‐phosphoinositide‐dependent protein kinase 1 (PDK1), is considered the master upstream lipid kinase of the PI3K‐Akt cascade. PDK1 functions to phosphorylate and partially activate Akt, triggering the activation of downstream effectors. However, the role of PDK1 in osteoclasts has yet to be clearly defined. In this study, we specifically deleted the PDK1 gene in osteoclasts using the cathepsin‐K promoter driven Cre‐LoxP system. We found that the specific genetic ablation of PDK1 in osteoclasts leads to an osteoclast‐poor osteopetrotic phenotype in mice. In vitro cellular assays further confirmed the impairment of osteoclast formation in response to RANKL by PDK1‐deficient bone marrow macrophage (BMM) precursor cells. PDK1‐deficient BMMs exhibited reduced ability to reorganize actin cytoskeleton to form a podosomal actin belt as a result of diminished capacity to fuse into giant multinucleated osteoclasts. Notably, biochemical analyses showed that PDK1 deficiency attenuated the phosphorylation of Akt and downstream effector GSK3β, and reduced induction of NFATc1. GSK3β is a reported negative regulator of NFATc1. GSK3β activity is inhibited by Akt‐dependent phosphorylation. Thus, our data provide clear genetic and mechanistic insights into the important role for PDK1 in osteoclasts.
The cellular stress response in fish exposed to salinity fluctuations
Authors: Evans Tyler G. , Kültz Dietmar 
Published: February 2020

AbstractSalinity stress occurs when salt concentration in the environment changes rapidly, for example because of tidal water flow, rainstorms, drought, or evaporation from small bodies of water. However, gradual changes in salt concentration can also cause osmotic stress in aquatic habitats if levels breach thresholds that reduce the fitness of resident organisms. The latter scenario is exemplified by climate change driven salinization of estuaries and by dilution of ocean surface salinity through changes in the water cycle. In this review, we discuss how fish employ the evolutionarily conserved cellular stress response (CSR) to cope with these different forms of salinity stress. Macromolecular damage is identified as the cause of impaired physiological performance during salinity stress and serves as the signal for inducing a CSR. Basic aspects of the CSR have been observed in fish exposed to salinity stress, including repair and protection of cellular macromolecules, reallocation of energy, cell cycle arrest, and in severe cases, programmed cell death. Osmosensing and signal transduction events that regulate these aspects of the CSR provide a link between environmental salinity and adaptive physiological change required for survival. The CSR has evolved to broaden the range of salinities tolerated by certain euryhaline fish species, but is constrained in stenohaline species that are sensitive to changes in environmental salinity. Knowledge of how the CSR diverges between euryhaline and stenohaline fish enables understanding of physiological mechanisms that underlie salt tolerance and facilitates predictions as to the relative vulnerabilities of different fish species to a rapidly changing hydrosphere.