bluuebunny/crossref_metadata_2025 huggingface dataset:
Does hospital competition improve efficiency? The effect of the patient choice reform in England
Authors: Longo Francesco , Siciliani Luigi , Moscelli Giuseppe , Gravelle Hugh
Published: February 2019

We use the 2006 relaxation of constraints on patient choice of hospital in the English NHS to investigate the effect of hospital competition on dimensions of efficiency including indicators of resource management (admissions per bed, bed occupancy rate, proportion of day cases, and cancelled elective operations) and costs (reference cost index for overall and elective activity, cleaning services costs, laundry and linen costs). We employ a quasi differences‐in‐differences approach and estimate seemingly unrelated regressions and unconditional quantile regressions with data on hospital trusts from 2002/2003 to 2010/2011. Our findings suggest that increased competition had mixed effects on efficiency. An additional equivalent rival increased admissions per bed by 1.1%, admissions per doctor by 0.9% and the proportion of day cases by 0.38 percentage points, but it also increased the number of cancelled elective operations by 2.5%.
All for one and one for all: A mechanism through which broad‐based employee stock ownership and employee‐perceived involvement practice create a productive workforce
Authors: Kim Andrea , Han Kyongji
Published: February 2019

Drawing on social identity theory, this research frames a multimediational model that delineates how broad‐based employee stock ownership (BESO) and employee‐perceived involvement practice in tandem yield a productive workforce at the organization level. In our theoretical model, we propose that social cohesion and voluntary turnover are collective attitudinal and behavioral outcomes resulting from the shared perception of we‐ness that employees experience through both participatory practices. Our path analysis of a multisource, time‐lagged dataset from 176 large U.S. companies revealed the sequential mediating roles of social cohesion and voluntary turnover between these organizational practices and labor productivity. Our theoretical claims and empirical evidence will contribute to a systematic understanding of how and why BESO and employee involvement leverage greater organizational productivity from employees.
Long noncoding RNA SOX2‐OT facilitates laryngeal squamous cell carcinoma development by epigenetically inhibiting PTEN via methyltransferase EZH2
Authors: Tai Yong , Ji Yuzi , Liu Fei , Zang Yanzi , Xu Dingyuan , Ma Song , Qin Litao , Ma Jiqing
Published: February 2019

Long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of various cancers, including laryngeal squamous cell carcinoma (LSCC). Recently, lncRNA Sox2 overlapping transcript (SOX2‐OT) has been identified as an oncogene in various cancers. However, the functional role and the regulatory mechanism of SOX2‐OT in LSCC remains unclear. In this study, we found that SOX2‐OT expression was increased and negatively correlated with PTEN expression in LSCC tissues. Furthermore, SOX2‐OT overexpression promoted LSCC cell proliferation, migration, invasion, and suppressed cell apoptosis in vitro, as well as facilitated the in vivo tumorigenicity. By contrast, SOX2‐OT silencing exerted the opposite effect. Mechanically, SOX2‐OT interacted with EZH2 and recruited EZH2 to induce H3K27me3 and epigenetically inhibited PTEN expression in LSCC cells. Additionally, EZH2 silencing and PTEN overexpression significantly abrogated the SOX2‐OT overexpression‐mediated promotion of LSCC cell malignant behavior. Collectively, our findings demonstrate that SOX2‐OT inhibits PTEN expression to facilitate LSCC development through EZH2‐mediated H3K27me3. © 2019 IUBMB Life, 71(9):1230–1239, 2019
Overexpression of KIF18A promotes cell proliferation, inhibits apoptosis, and independently predicts unfavorable prognosis in lung adenocarcinoma
Authors: Zhong Yonglong , Jiang Lingyu , Lin Hui , Li Xiangwei , Long Xiaomao , Zhou Yifan , Li Baijun , Li Zongrong
Published: February 2019

Kinesin family member 18A (KIF18A), as a member of the kinesin superfamily, is significantly overexpressed and abnormally functions in various human cancers. But, its expression profiling in the lung adenocarcinoma (LUAD) remains unclear. In the present work, using the data derived from the Cancer Genome Atlas (TCGA), we assessed the expression pattern and prognostic value of KIF18A in LUAD. In addition, we analyzed the underlying mechanism of its gene dysregulation. Experimental and bioinformatic analysis results showed that KIF18A expression was dramatically increased in LUAD tissues compared with the normal counterparts. Moreover, the patients with high KIF18A expression had significantly poorer overall survival (OS) and recurrence‐free survival (RFS). Univariate and multivariate analyses indicated that increased KIF18A expression was independently associated with unfavorable OS and RFS. In addition, by analyzing deep sequencing data from TCGA‐LUAD, we found that KIF18A mutation was detected in 2.6% of LUAD cases, and increased KIF18A expression was associated with genetic amplification rather than DNA methylation. Moreover, gene co‐expression network analysis revealed that a total of 339 KIF18A co‐expressed genes were detected and enriched in several tumor‐related pathways, especially cell cycle. Knockdown of KIF18A significantly inhibited cell proliferation in vitro and in vivo. Furthermore, silencing KIF18A induced LUAD cells apoptosis and arrested the cell cycle in the G2/M phase. KIF18A promotes cell proliferation, inhibits apoptosis, and is a valuable prognostic predictor and potential therapeutic target for the patients with LUAD. © 2019 IUBMB Life, 2019
Molecular interactions of chlorpyrifos and its environmental degradation products with human sex hormone‐binding globulin: an in silico study
Authors: Hazarika Jnyandeep , Ganguly Mausumi , Mahanta Rita
Published: February 2019

In recent years, there has been a widespread interest and awareness about health issues posed by endocrine‐disrupting chemicals present in the environment. These chemicals, often present in food and many consumer products, can interfere with hormone biosynthesis and metabolism and may result in deviation from normal homeostatic control. Chlorpyrifos (CPF), a major endocrine‐disrupting chemical is used worldwide as an agricultural insecticide against a broad spectrum of insect pests in rice cultivation and to control termites. The insecticide mostly undergoes environmental degradation to chlorpyrifos‐oxon (CPYO), des‐ethyl chlorpyrifos (DEC), 3,5,6‐trichloro‐2‐methoxypyridine (TMP) and 3,5,6‐trichloro‐2‐pyridinol (TCP). Results from several epidemiological studies suggest that exposure to CPF can result in reproductive disorders, including infertility in male and female. Sex hormone‐binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The objective of the present study involved computational approaches to apprehend the mechanism of molecular interaction of CPF and its four degradation products (CPYO, DEC, TMP, TCP) with human SHBG using molecular docking simulation. All five compounds (CPF, CPYO, DEC, TMP, TCP) showed high binding affinity with SHBG; however, the binding affinity values were higher (more negative) for CPF, CPYO, DEC and TMP than for TCP indicating that CPF, CPYO, DEC and TMP formed a tight interaction with SHBG. From the results obtained with the docking analysis, it can be opined that CPF, CPYO, DEC and TMP could possibly act as potential endocrine disruptors for androgen signaling.
Obesity and Bone Health Revisited: A Mendelian Randomization Study for Koreans
Authors: Lee Soo Ji , Lee Joo-Yeon , Sung Joohon
Published: February 2019

Epidemiologic studies have replicated positive associations between obesity and bone health, but their mechanisms are still debatable. We aimed to scrutinize an association between bone health and obesity using genetic instrumental variables (IVs) with the distinction of general versus abdominal obesity. We selected independent IVs of body mass index (BMI) and BMI-adjusted waist circumference (aWC, a proxy of a central fat distribution) by combining novel genomewide searches from the Korean Genome Epidemiology Study (KoGES) consortium and existing reports. We evaluated the associations of obesity indices with bone health measures for weight-bearing and non–weight-bearing bones, applying standard Mendelian randomization analyses. The IVs for BMI and aWC selected from KoGES cohort studies (n = 14,389) explained its own trait only, negating the mutual correlation at the phenotypic level. Two-stage least squares analyses using an independent cohort study (n = 2507, mean age = 44.4 years, men = 44.3%) showed that BMI but not aWC was positively associated with bone mineral density (BMD for weight-bearing bones: 0.063 ± 0.016 g/cm2 per one standard deviation increase in BMI), implying the fat distribution might be neutral. The association was weaker for non–weight-bearing bones (BMI on BMD: 0.034 ± 0.011 g/cm2), and for postmenopausal women the association was absent. Obesity increased both bone area and bone mineral content (BMC) to a lesser degree, but the increase in BMC was not evident for menopausal women. When we stratified the weight into lean body mass and fat mass, the increase in BMD was more evident for lean body mass, and fat mass showed a beneficial role only for men and premenopausal women. Our findings suggest that bone health might gain little from obesity, if any, through its added weight, and other means to prevent bone loss would be essential for postmenopausal women. © 2019 American Society for Bone and Mineral Research.
Functional integrity of the shoulder joint and pectoralis major following subpectoral implant breast reconstruction
Authors: Leonardis Joshua M. , Lyons Daniel A. , Giladi Aviram M. , Momoh Adeyiza O. , Lipps David B.
Published: February 2019

Subpectoral implants for breast reconstruction after mastectomy requires the surgical disinsertion of the sternocostal fiber region of the pectoralis major. This technique is associated with significant shoulder strength and range of motion deficits, but it is unknown how it affects the underlying integrity of the shoulder joint or pectoralis major. The aim of this study was to characterize the long‐term effects of this reconstruction approach on shoulder joint stiffness and pectoralis major material properties. Robot‐assisted measures of shoulder strength and stiffness and ultrasound shear wave elastography images from the pectoralis major were acquired from 14 women an average of 549 days (range: 313–795 days) post reconstruction and 14 healthy, age‐matched controls. Subpectoral implant patients were significantly weaker in shoulder adduction (p < 0.001) and exhibited lower shoulder stiffness when producing submaximal adduction torques (p = 0.004). The underlying material properties of the clavicular fiber region of the pectoralis major were altered in subpectoral implant patients, with significantly reduced shear wave velocities in the clavicular fiber region of the pectoralis major when generating adduction torques (p = 0.023). The clinical significance of these findings are that subpectoral implant patients do not fully recover shoulder strength or stability in the long‐term, despite significant recovery time, and substantial shoulder musculature left intact. The impact of these procedures extends to the remaining, intact volume of the pectoralis major. Optimization of shoulder function should be a key aspect of the post‐reconstruction standard of care. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1610–1619, 2019.
Clinical efficacy of preoperative 3D planning for reducing surgical errors during open‐wedge high tibial osteotomy
Authors: Kuriyama Shinichi , Morimoto Naoki , Shimoto Takeshi , Takemoto Mitsuru , Nakamura Shinichiro , Nishitani Kohei , Ito Hiromu , Matsuda Shuichi , Higaki Hidehiko
Published: February 2019

Increases in posterior tibial slope (PTS) with open‐wedge high tibial osteotomy (OWHTO) are often related to two surgical errors: Symmetric opening of the osteotomy gap and a tendency to open the gap from the anteromedial direction. The study objective was to define trends in these two errors using computer simulation and clinical effects of their countermeasures. First, 60 knees with varus deformity were assessed with three‐dimensional (3D) planning using computed tomography to allow for the mechanical axis to pass through a point at 62.5% of the width of the tibial plateau, defined as the weight‐bearing line percentage (WBL%). Anterior and posterior widths of the opening gap to maintain PTS were measured. The effect on PTS when osteotomy gaps were opened from the anteromedial direction up to 30° was evaluated. Mean anterior width (y) was 6.6 mm (range, 2.2–10.9) and mean posterior width (x) was 9.1 mm (range, 3.9–15.7), which can be expressed as y = 0.75x − 0.24. Opening gaps from the anteromedial direction at 10°, 20°, and 30° led to a mean PTS increase of 1.9°, 3.9°, and 5.6°, respectively. In most cases, WBL% with anteromedial opening at 30° passed through a point at less than 60%. In 47 knees that underwent OWHTO using 3D planning, postoperative coronal and sagittal bone corrections were mostly accurate. However, postoperative WBL% was negatively correlated with correction angle because of difficulties in predicting medial joint tightness. Preoperative 3D planning for OWHTO can reduce surgical errors, but postoperative WBL% remains variable. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Application of microwave and ohmic heating for pasteurization of cantaloupe juice: microbial inactivation and chemical properties
Authors: Hashemi Seyed Mohammad Bagher , Gholamhosseinpour Aliakbar , Niakousari Mehrdad
Published: February 2019

BACKGROUND

Cantaloupe melon (Cucumis melo L.) is one of the most important dessert fruits and is cultivated in many countries of the world. The effects of microwave (400 and 800 W for 110 s), ohmic (100 and 200 V for 110 s) and conventional heating (27–75 °C for 30 min) treatments on inactivation of Escherichia coli, Salmonella Typhimurium, S. Enteritidis and Staphylococcus aureus pathogens; pH and degradation of vitamin C, β‐carotene and phenolic compounds of cantaloupe juice were investigated.

RESULTS

As time passed, all of the treatments resulted in significant (P ≤ 0.05) decreases in the number of pathogens and vitamin C, β‐carotene and phenolic compound content, whereas the pH of samples did not show significant changes. The mentioned parameters were more reduced by increasing the power, voltage and temperature of ohmic, microwave and conventional heating treatments, respectively. Comparison of the results for conventional heating with those of ohmic and microwave heating revealed that the complete inactivation time of pathogens by the two latter treatments was much shorter than that of the former. After 20 s, the effect of ohmic heating at 200 V on decreasing vitamin C content was significantly (P ≤ 0.05) higher than that of the other treatments. The amounts of β‐carotene and phenolic compounds showed the most reduction under 800 W microwave treatment.

CONCLUSION

The results obtained for conventional, ohmic and microwave heating treatments indicated a higher degradation of β‐carotene and phenolic compounds and a lower loss of vitamin C in the former. © 2019 Society of Chemical Industry
Pulse‐width modulation with current uniformization for AM‐OLED micro‐displays on Si LSI chips
Authors: Kimura Mutsumi , Nishinohara Daisuke , Nishiyori Tomoya , Suzuki Daisuke , Sawamura Shigeki , Kato Masakazu
Published: February 2019

We have developed pulse‐width modulation (PWM) with current uniformization for active‐matrix organic light‐emitting diode (AM‐OLED) micro‐displays on Si large‐scale integration (LSI) chips. This driving method can simultaneously solve luminance unevenness and image sticking due to characteristic deviations and degradations of driving transistors and OLEDs. With the use of circuit simulation, it is verified that the PWM with current uniformization (PWM‐CU) can simultaneously achieve precise gray scale and exceedingly improve luminance uniformity. Moreover, an actual panel is designed and fabricated, where the OLEDs are layered on the Si LSI chip. It is found that the luminance uniformity can be improved within 2% to 3%. It is meaningful that the correct images can be displayed using the PWM‐CU for the first time for AM‐OLED micro‐displays on Si LSI chips.
The “Skinny” on Assessment and Utilization of Steatotic Liver Grafts: A Systematic Review
Authors: Croome Kristopher P. , Lee David D. , Taner C. Burcin
Published: February 2019

The frequency at which steatotic deceased donor liver grafts are encountered will likely continue to increase. Utilization of liver grafts with moderate‐to‐severe steatosis for liver transplantation (LT) has been previously shown to be associated with increased rates of primary nonfunction and decreased recipient survival. In order to better inform clinical decision making and guide future research, critical evaluation of the literature on donor liver steatosis and posttransplantation outcome is needed. This literature review aims to provide the “skinny” on using deceased donor steatotic livers for LT.
Smart Delivery Systems Based on Poly(glycidyl methacrylate)s‐Coated Organic/Inorganic Core–Shell Nanohybrids
Authors: Tan Li‐Li , Shang Li
Published: February 2019

Smart delivery systems have gained momentum over the last few decades due to their potential to realize enhanced therapeutic efficacy. Poly(glycidyl methacrylate)s (PGMAs), which spring up like mushrooms, have drawn great attention in the theranostics field, especially in multifunctional theranostic systems. The marriage of PGMAs with functional inorganic cores is expected to integrate diagnosis (e.g., fluorescence, X‐ray computed tomography, magnetic resonance, photoacoustic and upconversion luminescence imaging), treatment, or multimodal synergistic therapies (e.g., chemotherapy, gene therapy, photothermal therapy) in one pot for personalized medicine. In this review, recent progress in various PGMA‐coated nanohybrids based on the type of integrated inorganic nanoparticle, including silica nanoparticles, magnetic nanoparticles, quantum dots, gold nanoparticles, gold nanorods, metal‐organic frameworks, cellulose nanocrystals, and their core‐shell nanostructures is systematically reviewed. Future work in this field is anticipated to be devoted to developing efficient real‐time‐imaging‐guided multimodal synergistic therapies.
The protective impact of betaine on the tissue structure and renal function in isoproterenol‐induced myocardial infarction in rat
Authors: Ghartavol Mohammad Maram , Gholizadeh‐Ghaleh Aziz Shiva , Babaei Ghader , Hossein Farjah Gholam , Hassan Khadem Ansari Mohammad
Published: February 2019

Background

Myocardial infarction is one of the most common life threatening diseases that may lead to renal disorders via oxidative stress and inflammation. Betaine is a safe and well‐tolerated compound exhibiting beneficial antioxidant and anti‐inflammatory properties. Previous studies have demonstrated protective effects of betaine against myocardial infarction and renal injury. This study aimed to investigate the protective effect of betaine on tissue structure and renal function after isoprenaline‐induced myocardial infarction in rats.

Methods

Fifty Wistar strain male albino rats, weighing 200 ± 10, were selected for the study. The animals were housed individually under standard environmental conditions (Light–dark cycle, temperature and constant humidity) for 1 week. After acclimatization, they were randomly divided into five groups. G1, G2, and G3 groups received betaine at doses of 50, 150, and 250 mg/kg body weight/day via gavage for a period of 60 days. After 60 days, isoprenaline is injected subcutaneously (200 mg/kg body weight). In the isoprenaline group (G4), the rats were injected with isoprenaline (200 mg/kg body weight) and the control group (G5) received a standard diet (Without isoprenaline). Then, isoproterenol solution was used for induction of myocardial infarction. At the end, the expression of nitric oxide synthase (iNOS) protein was detected using immunohistochemical analysis and kidney tissues were assessed via histopathological analysis. In addition, serum level of TNF‐α and creatinine level were measured via ELISA test and colorimetric methods, respectively.

Results

The results of our study indicate that isoproterenol‐induced renal histopathological injury without changing creatinine level. Betaine has protective effects against renal injuries induced by isoprenaline and the expression of nitric oxide synthase (nNOS) protein showed no significant difference in all groups. Further, betaine reduced TNF‐α level significantly.

Conclusion

According to our results, betaine has protective effects on isoprenaline‐induced renal failure via a decrease in TNF‐α level and nitric oxide synthase.
Modeling the Solubility of C70 Fullerenes in Diverse Solvents: Role of Quantum‐mechanical Descriptors
Authors: Lata Suman , Vikas
Published: February 2019

Solubility of fullerenes in diverse solvents is difficult to model owing to the involvement of inherent quantum‐mechanical interactions. This work proposes pure quantum mechanical models for predicting the solubility of C70 fullerenes. The models are developed using single‐molecule quantum mechanical properties of solvents,which includes electron‐correlation based descriptors accounting for the instantaneous inter‐electronic interactions responsible for the origin of these properties. The external predictivity of the models was validated using an external prediction set of compounds not exposed to the model during its development. The most influential factor affecting the solubility was found to be electron‐correlation contribution to the energy of highest occupied molecular orbital of solvents, which in fact, has been analyzed to suppress the solubility of fullerenes. However, the polarizability of the solvents, particularly that due to the quantum‐mechanical exchange interactions between the electrons, is observed to drive the solubility of C70 fullerenes. The present work also found several other quantum mechanical properties affecting the solubility of fullerenes, which pay valuable insights towards the origin of the solubility of carbon‐based nano‐materials.
Macular Xanthophylls and Event‐Related Brain Potentials among Overweight Adults and Those with Obesity
Authors: Edwards Caitlyn G. , Walk Anne M. , Cannavale Corinne N. , Thompson Sharon V. , Reeser Ginger E. , Holscher Hannah D. , Khan Naiman A.
Published: February 2019

Scope

Macular accumulation of xanthophyll carotenoids (lutein, zeaxanthin) is known to have neuroprotective potential, yet their influence on cognition among overweight adults and those with obesity remains limited. This study examines the impact of macular xanthophylls on attentional resource allocation and information processing speed among adults with BMI ≥ 25 kg m−2.

Methods and Results

Adults between 25 and 45 years (N = 101) complete heterochromatic flicker photometry to determine macular pigment optical density (MPOD). Event‐related brain potentials are recorded during a visual oddball task. Amplitude and latency of the N2 and P3 indexed attentional resource allocation and information processing speed. Covariates included age, sex, education, intelligence quotient (IQ), %Fat (DXA), and dietary lutein and zeaxanthin (Diet History Questionnaire II). MPOD is inversely related to P3 peak amplitude during standard trials and P3 peak latency during target trials. Therefore, individuals with higher MPOD dedicate fewer attentional resources when attentional demands are low while exhibiting faster information processing speed when attentional demands are increased. Further, MPOD is inversely related to the N2 mean amplitude during targets, signifying greater inhibitory control.

Conclusion

These findings are the first to link macular xanthophylls to neuroelectric indices of attentional and inhibitory control among adults with overweight and obesity.
The Human Fecal Microbiota Metabolizes Foodborne Heterocyclic Aromatic Amines by Reuterin Conjugation and Further Transformations
Authors: Beer Falco , Urbat Felix , Franz Charles M. A. P. , Huch Melanie , Kulling Sabine E. , Bunzel Mirko , Bunzel Diana
Published: February 2019

Scope

Heterocyclic aromatic amines (HAAs) are process‐induced food contaminants with high mutagenic and/or carcinogenic potential. Although the human gut microbiota is known to affect the metabolism of dietary constituents, its impact on HAA metabolism and toxicity has been little studied. Here, the glycerol‐dependent metabolism of seven foodborne HAAs (AαC, Trp‐P‐1, harman, norharman, PhIP, MeIQx, and MeIQ) by the human fecal microbiota is investigated.

Methods and results

As analyzed by HPLC–DAD/FLD, the extent of conversion is strongly dependent on glycerol supplementation and HAA structure. AαC (60–100%) and the 2‐aminoimidazoazarenes (up to 58%) are especially prone to microbial conversion. Based on high‐resolution MS and/or NMR spectroscopy data, 70 fecal metabolites are identified in total, mainly formed by chemical reactions with one or two molecules of microbially derived reuterin. Moreover, it has been demonstrated that the human fecal microbiota can further transform reuterin adducts by reduction and/or hydroxylation reactions. Upon isolation, some reuterin‐induced HAA metabolites appear to be partially unstable, complicating structural identification.

Conclusion

The formation of microbial metabolites needs to be incorporated into risk assessment considerations for HAAs in human health. In this study, several HAA metabolites, mainly reuterin‐dependent, are identified in vitro, providing the basis for future human studies investigating microbial HAA metabolism.
Induction of Autophagy and Activation of SIRT‐1 Deacetylation Mechanisms Mediate Neuroprotection by the Pomegranate Metabolite Urolithin A in BV2 Microglia and Differentiated 3D Human Neural Progenitor Cells
Authors: Velagapudi Ravikanth , Lepiarz Izabela , El‐Bakoush Abdelmeneim , Katola Folashade O. , Bhatia Harsharan , Fiebich Bernd L. , Olajide Olumayokun A.
Published: February 2019

Scope

Urolithin A is an anti‐inflammatory and neuroprotective gut‐derived metabolite from ellagitannins and ellagic acid in pomegranate, berries, and nuts. The roles of SIRT‐1 and autophagy in the neuroprotective activity of urolithin A are investigated.

Methods and results

Analyses of culture supernatants from lipopolysaccharide‐stimulated BV2 microglia show that urolithin A (2.5–10 µm) produced significant reduction in the production of nitrite, tumor necrosis factor (TNF)‐α and IL‐6. The anti‐inflammatory effect of the compound is reversed in the presence of sirtuin (SIRT)‐1 and the autophagy inhibitors EX527 and chloroquine, respectively. Protein analyses reveal reduction in p65 and acetyl‐p65 protein. Treatment of BV2 microglia with urolithin A results in increased SIRT‐1 activity and nuclear protein, while induction of autophagy by the compound is demonstrated using autophagy fluorescent and autophagy LC3 HiBiT reporter assays. Viability assays reveal that urolithin A produces a neuroprotective effect in APPSwe‐transfected ReNcell VM human neural cells, which is reversed in the presence of EX527 and chloroquine. Increase in both SIRT‐1 and autophagic activities are also detected in these cells following treatment with urolithin A.

Conclusions

It has been proposed that SIRT‐1 activation and induction of autophagy are involved in the neuroprotective activity of urolithin A in brain cells.
Maternal Supplementation with β‐Carotene During Pregnancy Disturbs Lipid Metabolism and Glucose Homoeostasis in F1 Female Mice
Authors: Guo Jiaojiao , Li Bingshui , Zuo Zhenghong , Chen Meng , Wang Chonggang
Published: February 2019

Scope

β‐Carotene (BC), a substitute for vitamin A, is widely used for its benefits. The present study investigates whether in‐utero BC administration can alter lipid and glucose homoeostasis in offspring.

Methods and results

Pregnant mice are supplemented with BC (1 mg kg−1 weight) by oral gavage once every 3 days, for a total of six doses. Increased visceral fat may be caused by up‐regulated PPARγ (peroxisome proliferator‐activated receptor gamma) and RXRα/β (retinoid X receptors) in liver and adipose tissue, and glucose intolerance is observed in F1 adult females prenatally supplemented with BC, while F1 males do not exhibit these symptoms. In females, increased serum leptin, resistin, and IL‐6 and reduced adiponectin, caused by visceral obesity, may result in downregulated insulin receptor signaling in muscle and further account for glucose intolerance. Increased pancreatic β‐cell mass might compensate for the downregulated insulin gene (ins2). Increased glucagon and α‐cell mass, accompanied by upregulated glucagon gene (gcg), might also be risk factors for the development of diabetes.

Conclusions

Maternal supplementation with BC disturbs lipid metabolism and induces glucose intolerance in F1 female mice, suggesting that BC supplementation during pregnancy should be used with caution.
Evaluating cause‐marketing campaigns in the Indian corporate landscape: The role of consumer skepticism and consumer attributions of firm's motive
Authors: Ratnakaran Sunitha T. , Edward Manoj
Published: February 2019

More and more business organizations are engaging in social initiatives to make a positive contribution to society. Cause marketing, such as CSR, is one of the many ways that firms can manifest social responsibility by pitching‐in where government solutions are few or takes time in implementation, and it is the only type that calls for consumer participation. Because customer participation is imperative for the success of the campaign, it must be designed to connect with consumers while also making them feel that corporate efforts are authentic and truly helping the cause and not exploitative of the social cause. Using fictitious brand, cause‐marketing campaigns were designed, and two studies were conducted to analyze the relationship between cause involvement, consumer attributions on firm's motive, and consumer attitudes towards cause campaigns, and if and how the relationship differs when consumer skepticism towards cause claims existed. Multivariate analysis performed for hypotheses testing suggests that cause involvement influenced campaign attitudes and the relationship was mediated by consumer attributions of firm's motive, and consumer skepticism towards cause campaigns affected the relationship.
A computational study into the origin of reactivity and selectivity of organocatalyzed [2 + 2] reactions between α,β‐unsaturated aldehydes and nitroolefins
Authors: Dong Minghua , Ji Ziyue , Zhang Beibei , Guo Chenchen , Jiao Mingyang , Chen Bo‐Zhen
Published: February 2019

The mechanisms of organocatalyzed [2 + 2] reactions between α,β‐unsaturated aldehydes and nitroolefins with various substituents were explored using the density functional theory M05‐2X method. The calculations indicate that all 14 reactions we studied proceed through a stepwise mechanism and most of them are predicted to be feasible both kinetically and thermodynamically. The feasibility of the catalyzed reactions is mainly attributed to that the formation of dienamines could significantly increase the highest occupied molecular orbital (HOMO) energy of α,β‐unsaturated aldehydes, while the substituents have less influence. Also, the H‐bonding interactions between the catalysts and nitroolefins play a key role in the regioselectivity, and the stronger H‐bond favors the 3,4‐reactivity. Besides, the chemoselectivity is also discussed.
Engineering Multifunctional Gold Decorated Dendritic Mesoporous Silica/Tantalum Oxide Nanoparticles for Intraperitoneal Tumor‐Specific Delivery
Authors: Kashfi‐Sadabad Raana , Gonzalez‐Fajardo Laura , Hargrove Derek , Ahmadi Bahar , Munteanu Daniel , Shahbazmohamadi Sina , Jay Michael , Lu Xiuling
Published: February 2019

Nonspecific high‐energy radiation for treatment of metastatic ovarian cancer is limited by damage to healthy organs, which can be mitigated by the use of radiosensitizers and image‐guided radiotherapy. Gold (Au) and tantalum oxide (TaOx) nanoparticles (NPs), by virtue of their high atomic numbers, find utility in the design of bimetallic NP systems capable of high‐contrast computed tomography (CT) imaging as well as a potential radiosensitizing effect. These two radio‐dense metals are integrated into dendritic mesoporous silica NPs (dMSNs) with radial porous channels for high surface‐area loading of therapeutic agents. This approach results in stable, monodispersed dMSNs with a uniform distribution of Au on the surface and TaOx in the core that exhibits CT attenuation up to seven times greater than iodine or monometallic dMSNs without either TaOx or Au. Tumor targeting is assessed in a metastatic ovarian cancer mouse model. Ex vivo micro‐CT imaging of collected tumors shows that these NPs not only accumulate at tumor sites but also penetrate inside tumor tissues. This study demonstrates that after intraperitoneal administration, rationally designed bimetallic NPs can simultaneously serve as targeted contrast agents for imaging tumors and to enhance radiation therapy in metastatic ovarian cancer.
A Riemann Problem Based Coupling Method for Predicting the Combustion of Propellant in a Gun Launching Process
Authors: Hu Chaobin , Zhang Xiaobing
Published: February 2019

Methods for improving the accuracy and guaranteeing the fidelity of numerical predictions are of great importance for physical problems accompanied by strong nonlinear multi‐physic interactions and extreme working conditions. The prediction of propellant combustion in a gun launching process is a typical example. A one‐dimensional two‐fluid model was utilized to govern the fluid field induced by the combustion. In order to guarantee the accuracy of the predictions, we utilized a Roe's scheme to solve the partial differential equations. To guarantee the accuracy of the moving boundaries in the expanding chamber, the coupling between the updating of the fluid field and the approximation of the mechanical interactions between the projectile and the barrel is realized based on the commercial software ABAQUS. The separate treatment of the advection and source terms in the split approach was verified through the agreement between the maximum value of the predicted average pressure in a closed bomb and the theoretical value. The coupled method dealing with the moving boundaries was validated by comparing the numerical results with the analytical results of a pressure‐driven piston case. Finally, the numerical method was applied to a large‐caliber gun. The predicted maximum pressure and the muzzle velocity agree well with experiments.
The Connection Between the Parameters of WLF Equation and of Arrhenius Equation
Authors: Bohn Manfred A.
Published: February 2019

The description of the change in characteristic temperatures of thermomechanical and viscoelastic properties of polymers and elastomers with deformation frequency or of temperature dependence of polymer properties is widely achieved by two equations: (1) the Williams‐Landel‐Ferry (WLF) equation and (2) the Arrhenius equation. Mostly the WLF equation is used. Often the distinction between the two descriptions is based on the argument: if volume processes play the key role, then WLF equation is the right one, if thermally activated processes play the key role, then Arrhenius equation is the right one. Both equations are based on the activation of processes, and always the temperature is the variable, which activate the processes. Both descriptions are methods to parameterize the temperature dependence of properties or the change of characteristic temperatures, as glass‐rubber transition temperature, with deformation rate. Also, the so‐called ‘volume processes’ are controlled by temperature, but the thermal activation can be small in energy to initiate the change in spatial position from one site to another for a molecule. This means both descriptions should be congruent. In this article, the congruence is shown and the relation between WLF parameters and Arrhenius parameters will be established. For this, a slight modification of the usual Arrhenius equation is necessary. Also, other descriptions are discussed in short: Doolittle equation and Vogel‐Fulcher equation, they were or are used to describe the change of viscosity with temperature in melts or solutions.
The Holographic Entropy Arrangement
Authors: Hubeny Veronika E. , Rangamani Mukund , Rota Massimiliano
Published: February 2019

We develop a convenient framework for characterizing multipartite entanglement in composite systems, based on relations between entropies of various subsystems. This continues the program initiated in [1], of using holography to effectively recast the geometric problem into an algebraic one. We prove that, for an arbitrary number of parties, our procedure identifies a finite set of entropic information quantities that we conveniently represent geometrically in the form of an arrangement of hyperplanes. This leads us to define the holographic entropy arrangement, whose algebraic and combinatorial aspects we explore in detail. Using the framework, we derive three new information quantities for four parties, as well as a new infinite family for any number of parties. A natural construct from the arrangement is the holographic entropy polyhedron which captures holographic entropy inequalities describing the physically allowed region of entropy space. We illustrate how to obtain the polyhedron by winnowing down the arrangement through a sieve to pick out candidate sign‐definite information quantities. Comparing the polyhedron with the holographic entropy cone, we find perfect agreement for 4 parties and corroborating evidence for the conjectured 5‐party entropy cone. We work with explicit configurations in arbitrary (time‐dependent) states leading to both simple derivations and an intuitive picture of the entanglement pattern.
Dopamine receptor antagonists induce differentiation of PC‐3 human prostate cancer cell‐derived cancer stem cell‐like cells
Authors: Lee Su In , Roney Md Saiful Islam , Park Jong Hyeok , Baek Ji‐Young , Park Jooyeon , Kim Sang Kyum , Park Song‐Kyu
Published: February 2019

Background

The objective of this study was to determine whether PC‐3 human prostate cancer cell‐derived cancer stem cells (CSC)‐like cells grown in a regular cell culture plate not coated with a matrix molecule might be useful for finding differentiation‐inducing agents that could alter properties of prostate CSC.

Methods

Monolayer cells prepared from sphere culture of PC‐3 cells were characterized for the presence of pluripotency and tumorigenicity. They were then applied to screen a compound library to find compounds that could induce morphology changes of cells. Mechanisms of action of compounds selected from the chemical library that induced the loss of pluripotency of cells were also investigated.

Results

C5A cells prepared from PC‐3 cell‐derived sphere culture expressed pluripotency markers such as Oct4, Sox2, and Klf4. C5A cells were highly proliferative. They were invasive in vitro and tumorigenic in vivo. Some dopamine receptor antagonists such as thioridazine caused reduction of pluripotency markers and tumorigenicity. Thioridazine, unlike promazine, inhibited phosphorylation of AMPK in a dose dependent manner. BML‐275, an AMPK inhibitor, also induced differentiation of C5A cells as seen with thioridazine whereas A769663, an AMPK activator, blocked its differentiation‐inducing ability. Transfection of C5A cells with siRNAs of dopamine receptor subtypes revealed that knockdown of DRD2 or DRD4 induced morphology changes of C5A cells.

Conclusions

Some dopamine receptor antagonists such as thioridazine can induce differentiation of CSC‐like cells by inhibiting phosphorylation of AMPK. Binding to DRD2 or DRD4 might have mediated the action of thioridazine involved in the differentiation of CSC‐like cells.
Effect of heterochiral inversions on the structure of a β‐hairpin peptide
Authors: Zerze Gül H. , Stillinger Frank H. , Debenedetti Pablo G.
Published: February 2019

We study computationally a family of β‐hairpin peptides with systematically introduced chiral inversions, in explicit water, and we investigate the extent to which the backbone structure is able to fold in the presence of heterochiral perturbations. In contrast to the recently investigated case of a helical peptide, we do not find a monotonic change in secondary structure content as a function of the number of L‐ to D‐inversions. The effects of L‐ to D‐inversions are instead found to be highly position‐specific. Additionally, in contrast to the helical peptide, some inversions increase the stability of the folded peptide: in such cases, we compute an increase in β‐sheet content in the aqueous solution equilibrium ensemble. However, the tertiary structures of the stable (folded) configurations for peptides for which inversions cause an increase in β‐sheet content show differences from one another, as well as from the native fold of the nonchirally perturbed β‐hairpin. Our results suggest that although some chiral perturbations can increase folding stability, chirally perturbed proteins may still underperform functionally, given the relationship between structure and function.
Mass spectrometric quantification of the binding ratio of metal‐based anticancer complexes with protein thiols
Authors: Han Yumiao , Guo Wei , Zheng Wei , Luo Qun , Wu Kui , Zhao Yao , Wang Fuyi
Published: February 2019

Rationale

The binding ratio of metal complexes with cysteinyl thiols in proteins plays an important role in deciphering the mechanisms of action of therapeutic metal complexes, but its analysis is still a significant challenge. In this work, a quantitative mass spectrometry method is developed to determine the binding ratio of metal‐based anticancer complexes with cysteines in human copper chaperone protein Atox1.

Methods

A novel strategy based on a thiol‐specific stable isotopic labelling reagent was developed to determine the binding ratio of metal‐based anticancer complexes, namely cisplatin and organometallic ruthenium complex [(η6‐biphenyl)RuCl(en)]PF6 (en = ethylenediamine), with the cysteinyl residues of Atox1.

Results

Both cisplatin and the ruthenium complex were reactive not only to Cys15 and/or Cys18, the copper(I) binding site of Atox1, but also to Cys44. The binding ratios of the ruthenium complex with the cysteinyl residues were much higher than those of cisplatin. However, the addition of copper(I) could markedly increase the binding ratios of cysteinyl residues of Atox1 with cisplatin, but not with the ruthenium complex.

Conclusions

This strategy can not only precisely determine the binding ratios of metal complexes to protein thiols, but also be helpful in distinguishing thiol‐binding sites from other binding sites of metal complexes in proteins. We expect wide application of this method to the research of covalent/coordinative interactions between metal complexes and protein thiols.
Advances in Graphene‐Based Liquid Cell Electron Microscopy: Working Principles, Opportunities, and Challenges
Authors: Ghodsi Seyed Mohammadreza , Megaridis Constantine M. , Shahbazian‐Yassar Reza , Shokuhfar Tolou
Published: February 2019

Imaging materials and biological structures in a liquid environment pose a significant challenge for conventional transmission electron microscopy (TEM) due to stringent requirement of ultrahigh vacuum design in the microscope column. The most recent liquid‐cell TEM technique, graphene liquid‐cell (GLC) microscopy, employs only layers of graphene to encapsulate liquid specimens. Recent efforts with GLC–TEM have demonstrated superior imaging resolution of beam‐sensitive specimens. Herein, the parameters that affect the quality of GLC analysis, including the graphene transfer onto TEM grids, are reviewed. Several important factors that affect the in situ TEM imaging of specimens, including the variations in GLC geometries and capillary pressure are discussed. The interaction between the electron beam and the liquid along with the possibility for artifacts or the formation of radical ions is also highlighted in this review. The scientific discoveries enabled by GLC–TEM in the areas of nucleation and growth of crystals, corrosion, battery science, as well as high‐resolution imaging of organelles and proteins are also briefly discussed. Finally, possible future research directions of GLC–TEM and the associated challenges are discussed. The synergistic effort to accomplish the proposed research directions has the potential to yield new discoveries in both materials and life sciences.
On repairable earthquake resisting archetypes with a view to resiliency objectives and assisted self‐centering
Authors: Grigorian Mark , Moghadam Abdolreza S. , Kamizi Mozhgan
Published: February 2019

Performance‐based seismic design, as an alternative to conventional methods of approach, has served engineers and the public rather well during the last two decades. Neither approach guaranties catastrophic collapse prevention nor post‐earthquake realignment and repairs (PERR) due to major seismic events. As a result, most code‐compliant buildings can be regarded as relatively safe but practically disposable. The paper presents a new philosophy that leads to sustainable design of new structures and the upgrading of existing earthquake resisting moment frames. Repairability‐based design (RBD) relies on softening and control rather than strength and resistance to elevate seismic performance to economically viable, physical collapse prevention, damage control, and post‐earthquake realignment and repairs. The new approach was inspired by design led analysis (DLA), performance control (PC), and recent developments in rocking core‐moment frame design. DLA is a displacement based method of analysis with built‐in results. PC is the ability to design a structure in such a way as to expect predetermined modes of response at certain stages of loading, extents of damage, and drift ratios. This paper advocates higher performance objectives than current codes of practice do. Several demonstrative examples have been provided.
Playful Literacies, Creativity, and Multilingual Practices
Authors: Yoon Haeny S.
Published: February 2019

Emergent language learners develop literacy through social interactions in multiple, overlapping communities: home, school, peer groups, and popular culture. The author focuses on how classrooms can be spaces that cultivate authentic literacy engagements while incorporating and valuing students’ existing language resources.