bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics of the reaction of ethanol and lauric acid catalyzed by deep eutectic solvent based on benzyltrimethylammonium chloride
Authors: Li Kun , Xue Weilan , Zeng Zuoxiang , Shi Xinyue
Published: September 2018

In this work, three types of deep eutectic solvents (DESs: BAC‐PTSA, BAC‐2PTSA, and BAC‐3PTSA) based on benzyltrimethylammonium chloride (BAC) were successfully synthesized by mixing benzyltrimethylammonium chloride with p‐toluenesulphonic acid monohydrate (PTSA) and used as catalysts for the esterification reaction of ethanol and lauric acid. The kinetics of the reaction of ethanol and lauric acid in the presence of DESs as catalysts was investigated systemically in the temperature range of 333.15–353.15 K. The influences of different parameters including type of DESs, reaction temperature, catalyst loading, and initial reactant molar ratio on the conversion of lauric acid were discussed. The kinetic experimental data obtained were successfully correlated by the pseudohomogeneous (PH) model based on the activities. Moreover, BAC‐3PTSA is easily synthesized and reused six times without any significant decrease in catalytic activity.
Artificial neural network‐genetic algorithm (ANN‐GA) based medium optimization for the production of human interferon gamma (hIFN‐γ) in Kluyveromyces lactis cell factory
Authors: Unni Silpa , Prabhu Ashish A. , Pandey Rajat , Hande Rohit , Veeranki Venkata Dasu
Published: September 2018

In the current investigation, we have adapted response surface methodology (RSM) and artificial neural network‐genetic algorithm (ANN‐GA) based optimization to develop a defined medium for maximizing human interferon gamma production from recombinant Kluyveromyces lactis (K. lactis). In the initial screening studies, sorbitol and glycine emerged as a carbon and nitrogen source respectively having higher influence on hIFN‐γ production. Substrate inhibition studies were performed by varying the initial substrate concentration, and we found maximum hIFN‐γ concentration at 50 g L−1 of sorbitol. Inhibition kinetics studies were carried out using 3 and 4‐parametric models. Among the estimated models, the Moser model was observed as the best fitted model followed by the Luong model with R2 values of 0.882 and 0.75, respectively. The model acceptability test was carried out using the extra sum of squares F‐test and Akaike information criterion (AIC). The Plackett‐Burman multifactorial design identified sorbitol, glycine, Na2HPO4, and MgSO4.7H2O as the parameters significantly influencing the hIFN‐γ production. Further, the Box‐Behnken design (BBD) followed by the artificial neural network coupled with genetic algorithm (ANN‐GA) was employed for the precise optimization of medium components. With ANN‐GA a maximum hIFN‐γ yield of 2.1 ±0.3 mg L−1 in shake flask level and 3.5 ±0.1 mg L−1 in reactor level was achieved. The findings of this study serve as a model for a process development strategy (bench scale to reactor scale) to achieve a high productivity of the desired protein from a microbial cell factory.
Health literacy and cancer self‐management behaviors: A scoping review
Authors: Papadakos Janet K. , Hasan Salwa M. , Barnsley Jan , Berta Whitney , Fazelzad Rouhi , Papadakos Christine J. , Giuliani Meredith E. , Howell Doris
Published: September 2018

Background

Increasing demands on health care systems require patients to take on more active roles in their health. Effective self‐management has been linked to improved health outcomes, and evidence shows that effective self‐management is linked to health literacy (HL). HL is an important predictor of successful self‐management in other chronic diseases but has had minimal testing in cancer.

Methods

A scoping review was conducted to examine and summarize what is known about the association between HL and self‐management behaviors and health service utilization in the cancer setting. The methodological framework articulated by Arksey and O’Malley was used and was further refined with the Joanna Briggs Institute methodology. Inclusion criteria included the following: peer review; publication in English; and adult patients and caregivers of all races, ethnicities, and cultural groups. Use of a validated instrument to measure HL was required.

Results

The search yielded 2414 articles. After the removal of duplicates and the performance of title scans and abstract reviews, the number was reduced to 44. Of the 44 full‐text articles reviewed, 17 met the inclusion criteria. A number of important self‐management behaviors and related outcomes were found to be associated with HL. These included the uptake of cancer screening, the receipt of prescribed chemotherapy, and a greater risk of postoperative complications.

Conclusions

This literature review shows that HL is associated with important self‐management behaviors in cancer. The implications of these associations for individuals with inadequate HL and for the health care system are significant. More research is needed to explore these associations.
Hospitalization by cytotoxic chemotherapy regimen among older women with stage IV breast cancer
Authors: Kehl Kenneth L. , Niu Jiangong , Chavez‐MacGregor Mariana , Giordano Sharon H.
Published: September 2018

Background

Older patients with cancer are at risk for increased side effects of treatment. Our goal was to inform treatment for older patients by analyzing the relationship between chemotherapy regimen and hospitalization among older women receiving palliative cytotoxic chemotherapy for breast cancer.

Method

We identified women aged 66‐99 years with stage IV de novo breast cancer diagnosed between 2010 and 2013 who received any of the 10 most common cytotoxic chemotherapy‐containing regimens in the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database. The primary outcome was hospitalization or death within 30 days of starting a new line of chemotherapy. Generalized linear mixed effects models with patient‐specific random effects were used for multivariable analysis of the association between chemotherapy regimen and this outcome. Additional covariates included number of prior lines of therapy; time since diagnosis; hormone receptor and HER2 status; sites of metastatic disease; and age, race, and marital status. The unit of analysis was each new line of chemotherapy.

Results

Of 972 lines of chemotherapy initiated among 693 patients, 188 (19%) were followed by hospitalization or death within 30 days. After adjustment, there was significant variation in this outcome by chemotherapy regimen (P = .03); compared with capecitabine, hospitalization/death rates were higher with cyclophosphamide + docetaxel (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.31‐5.59), cyclophosphamide + doxorubicin (OR, 2.45; 95% CI, 1.19‐5.03), docetaxel (OR, 2.49; 95% CI, 1.19‐5.21), and gemcitabine (OR, 3.51; 95% CI, 1.72‐7.19).

Conclusion

Treatment regimen was associated with significant variation in 30‐day hospitalization or death among older women receiving cytotoxic chemotherapy for stage IV de novo breast cancer.
Fluorescence Activated Cell Sorting (FACS) in Genome‐Wide Genetic Screening of Membrane Trafficking
Authors: Menasche Bridget L. , Crisman Lauren , Gulbranson Daniel R. , Davis Eric M. , Yu Haijia , Shen Jingshi
Published: September 2018

About one‐third of cellular proteins in eukaryotic cells are localized to membrane‐enclosed organelles in the endomembrane system. Trafficking of these membrane proteins (including soluble lumenal proteins) among the organelles is mediated by small sac‐like vesicles. Vesicle‐mediated membrane trafficking regulates a broad range of biological processes, many of which are still poorly understood at the molecular level. A powerful approach to dissect a vesicle‐mediated membrane trafficking pathway is unbiased genome‐wide genetic screening, which only recently became possible in mammalian cells with the isolation of haploid human cell lines and the development of CRISPR‐Cas9 genome editing. Here, we describe a FACS‐based method to select populations of live mutant cells based on the surface levels of endogenous proteins or engineered reporters. Collection of these mutant populations enables subsequent deep sequencing and bioinformatics analysis to identify genes that regulate the trafficking pathway. This method can be readily adapted to genetically dissect a broad range of mammalian membrane trafficking processes using haploid genetics or CRISPR‐Cas9 screens. © 2018 by John Wiley & Sons, Inc.
Locally private Jaccard similarity estimation
Authors: Yan Ziqi , Wu Qiong , Ren Meng , Liu Jiqiang , Liu Shaowu , Qiu Shuo
Published: September 2018

Jaccard Similarity has been widely used to measure the distance between two sets (or preference profiles) owned by two different users. Yet, in the private data collection scenario, it requires the untrusted curator could only estimate an approximately accurate Jaccard similarity of the involved users but without being allowed to access their preference profiles. This paper aims to address the above requirements by considering the local differential privacy model. To achieve this, we initially focused on a particular hash technique, MinHash, which was originally invented to estimate the Jaccard similarity efficiently. We designed the PrivMin algorithm to achieve the perturbation of MinHash signature by adopting Exponential mechanism and build the Locally Differentially Private Jaccard Similarity Estimation (LDP‐JSE) protocol for allowing the untrusted curator to approximately estimate Jaccard similarity. Theoretical and empirical results demonstrate that the proposed protocol can retain a highly acceptable utility of the estimated similarity as well as preserving privacy.
Research on exchange rate pass‐through effect based on artificial intelligence approach
Authors: Chen Hong , Hu WenZhe
Published: September 2018

Artificial intelligence is widely believed to reshape many industries in the future. This paper analyzes the chaotic characteristics of Chinese export price index, exchange rate data, and studies the predictive ability of the neural network model in exchange rate passthrough (ERPT) prediction. The Hermite neural network model, one of artificial intelligence models, is selected to forecast the rate of pass‐through effect. Hermite neural network model demonstrates a superior forecasting accuracy, and its forecasting error is less than that of the general neural network model.
Heterojunction and Oxygen Vacancy Modification of ZnO Nanorod Array Photoanode for Enhanced Photoelectrochemical Water Splitting
Authors: Long Xuefeng , Li Feng , Gao Lili , Hu Yiping , Hu Haiguo , Jin Jun , Ma Jiantai
Published: September 2018

Application of ZnO in the field of photoelectrochemical water splitting is limited because of its wide‐band‐gap and high recombination rate. Herein is reported the design of an efficient ZnO photoanode deposited with CoOx nanoparticles to achieve a heterojunction and oxygen vacancies. The CoOx nanoparticles with abundant oxygen vacancies were anchored onto the nanorod arrays by spin coating and calcination followed by a solvothermal treatment. CoOx nanoparticles serve the dual function of forming a p‐n heterojunction to facilitate the separation of photogenerated carriers, and act as a cocatalyst to decrease water oxidation barrier. Finally, oxygen vacancies increase the number of active redox sites and act as hole traps, enabling their migration to the electrode/electrolyte interface. The composite photoanode exhibits a high incident photon‐to‐current conversion efficiency (76.7 % at 350 nm), which is twice that of pristine ZnO, and a photoconversion efficiency of 0.68 % (0.73 V versus RHE). The current approach can be expanded to fabricate other efficient photocatalysts.
NAD+‐Dependent Enzymatic Route for the Epimerization of Hydroxysteroids
Authors: Tonin Fabio , Otten Linda G. , Arends Isabel W. C. E.
Published: September 2018

Epimerization of cholic and chenodeoxycholic acid (CA and CDCA, respectively) is a notable conversion for the production of ursodeoxycholic acid (UDCA). Two enantiocomplementary hydroxysteroid dehydrogenases (7α‐ and 7β‐HSDHs) can carry out this transformation fully selectively by specific oxidation of the 7α‐OH group of the substrate and subsequent reduction of the keto intermediate to the final product (7β‐OH). With a view to developing robust and active biocatalysts, novel NADH‐active 7β‐HSDH species are necessary to enable a solely NAD+‐dependent redox‐neutral cascade for UDCA production. A wild‐type NADH‐dependent 7β‐HSDH from Lactobacillus spicheri (Ls7β‐HSDH) was identified, recombinantly expressed, purified, and biochemically characterized. Using this novel NAD+‐dependent 7β‐HSDH enzyme in combination with 7α‐HSDH from Stenotrophomonas maltophilia permitted the biotransformations of CA and CDCA in the presence of catalytic amounts of NAD+, resulting in high yields (>90 %) of UCA and UDCA.
The association between perinatal hypoxia exposure and externalizing symptoms and children’s decision making in conditions of uncertainty is moderated by DRD2 genotype
Authors: White Roisin , Gatzke‐Kopp Lisa M. , Ryan Patrick J. , Lydon‐Staley David M.
Published: September 2018

Variants of the DRD2 Taq1A polymorphism, which have been shown to result in functional differences in dopamine D2 receptors (D2R), have been linked to various externalizing outcomes in adults. However, the neurobiological processes that contribute to these associations are not well understood. The current study investigates gene × environment effects on teacher‐rated externalizing behaviors and probabilistic decision making in a sample of 333 children (age 9) enrolled in an ongoing longitudinal study. Findings indicate that externalizing behaviors increased as a function of hypoxic exposure only among individuals carrying the A1 (A1+) allele. Results also indicate that willingness to pursue reward under conditions of maximum uncertainty (50% probability) decreased as a function of hypoxic exposure only among A1− individuals. Among A1 carriers, no association between probability decision making and hypoxic exposure emerged. These findings suggest that hypoxia could influence neural development through different biological pathways depending on D2 receptor genotype, and provide insight into the development of individual differences in behavior and decision making.
Double electroporation in two adjacent tissues in chicken embryos
Authors: Draga Margarethe , Pröls Felicitas , Scaal Martin
Published: September 2018

In ovo electroporation is a well established method to introduce transgenes into a number of tissues in chicken embryos, e.g., neural tissue, limb mesenchyme, and somites. This method has been widely used to investigate cell lineage, cell morphology, and molecular pathways by localized expression of fluorescent reporter constructs. Furthermore gain‐ and loss‐of‐function experiments can be performed by electroporating transgenes or gene‐silencing constructs. We have developed a new technique to electroporate tissues positioned opposite to each other with different plasmids using an electroporation chamber. As proof of principle, we electroporated the dorsal surface ectoderm with a reporter construct expressing mCherry and the subjacent somites with a reporter construct expressing EGFP. This double‐electroporation technique allows investigation of the localization of two different proteins of interest in two adjacent tissues and will be useful to examine the cellular and molecular interaction of neighboring structures during embryonic development. Developmental Dynamics 247:1211–1216, 2018. © 2018 Wiley Periodicals, Inc.
Chromosome Missegregation and Aneuploidy Induction in Human Peripheral Blood Lymphocytes In vitro by Low Concentrations of Chlorpyrifos, Imidacloprid and α‐Cypermethrin
Authors: Mužinić Vedran , Ramić Snježana , želježić Davor
Published: September 2018

Chlorpyrifos, imidacloprid, and α‐cypermethrin are some of the most widely used insecticides in contemporary agriculture. However, their low‐dose, nontarget genotoxic effects have not been extensively assayed. As one of the most relevant cancer biomarkers, we aimed to assess the aneuploidy due to chromosome missegregation during mitosis. To aim it we treated human lymphocytes in vitro with three concentrations of insecticides equivalents relevant for real scenario exposure assessed by regulatory agencies. We focused on chlorpyrifos as conventional and imidacloprid and α‐cypermethrin as sustainable use insecticides. Cytokinesis‐blocked micronucleus assay was performed coupled with fluorescence in situ hybridization (FISH) with directly labeled pancentromeric probes for chromosomes 9, 18, X and Y. None of the insecticides induced significant secondary DNA damage in terms of micronuclei (MN), nuclear buds (NB), or nucleoplasmic bridges (NPB). However, significant disbalances in chromosomes 9, 18, X and Y, and in insecticide‐treated cells has been observed. According to recent studies, these disbalances in chromosome numbers may be atributted to defect sister chromatid cohesion which contribute to the increase of chromosome missegregation but not to micronuclei incidence. We conclude that tested insecticidal active substances exert chromosome missegregation effects at low concentrations, possibly by mechanism of sister chromatid cohesion. These findings may contribute to future risk assesments and understanding of insecticide mode of action on human genome. Environ. Mol. Mutagen. 60:72–84, 2019. © 2018 Wiley Periodicals, Inc.
Small RNA sequencing of sessile serrated polyps identifies microRNA profile associated with colon cancer
Authors: Kanth Priyanka , Hazel Mark W. , Boucher Kenneth M. , Yang Zhihong , Wang Li , Bronner Mary P. , Boylan Katherine E. , Burt Randall W. , Westover Michelle , Neklason Deborah W. , Delker Don A.
Published: September 2018

Sessile serrated adenoma/polyps (SSA/Ps) of the colon account for 20–30% of all colon cancers. Small non‐coding RNAs, including microRNAs (miRNAs), may function as oncogenes or tumor suppressor genes involved in cancer development. Small RNA sequencing (RNA‐seq) was used to characterize miRNA profiles in SSA/Ps, hyperplastic polyps (HPs), adenomatous polyps and paired uninvolved colon. Our 108 small RNA‐seq samples' results were compared to small RNA‐seq data from 212 colon cancers from the Cancer Genome Atlas. Twenty‐three and six miRNAs were differentially expressed in SSA/Ps compared to paired uninvolved colon and HPs, respectively. Differential expression of MIR31‐5p, MIR135B‐5p and MIR378A‐5p was confirmed by RT‐qPCR. SSA/P‐specific miRNAs are similarly expressed in colon cancers containing genomic aberrations described in serrated cancers. Correlation of miRNA expression with consensus molecular subtypes suggests more than one subtype is associated with the serrated neoplasia pathway. Canonical pathway analysis suggests many of these miRNAs target growth factor signaling pathways.
Long‐term relationships between screening rates, breast cancer characteristics, and overdiagnosis in US counties, 1975–2009
Authors: Harding C. , Pompei F. , Burmistrov D. , Wilson R.
Published: September 2018

Effects of mammography screening in the general population are disputed. Screening rates differ greatly between US counties, providing a natural opportunity to investigate effects of screening. We compared mammography screening rates with the types and outcomes of breast cancers diagnosed in US counties. The county screening rate was defined as the proportion of women age ≥40 with ≥1 mammogram in the past 2 years (range, 34–91%). Two periods were analyzed: 1975–2009 (612,941 breast cancer cases, 195 counties) and 1996–2009 (645,057 cases, 211–547 counties). Multiple signs of overdiagnosis were observed: First, breast cancer incidence increased as screening became common. Second, incidence stopped increasing once screening rates stabilized. Third, the increases in incidence were limited to age groups receiving screening. Fourth, the increases were larger in counties where screening became more common. Fifth, the increases were limited to small and early‐stage breast cancers (which are consistent with overdiagnosis). Sixth, compensatory reductions in large and advanced‐stage breast cancers were much smaller than the increases. Difference‐in‐differences regression analysis suggested 31% (95% CI: 28–34%) of breast cancers diagnosed in 1996–2009 were overdiagnosed. Screening rates correlated with increased incidence for all hormone receptor statuses, HER2 statuses, and grades. Reductions in breast cancer mortality during 1975–2009 were similar in screened and unscreened age groups. Overall, we found repeated signs that breast cancer overdiagnosis is widespread in the US, but the biological nature of overdiagnosed tumors remains unclear. Mortality benefits of screening, though they may be present and substantial, could not be detected at the population level.
Microbiota‐derived lipopolysaccharide retards chondrocyte hypertrophy in the growth plate through elevating Sox9 expression
Authors: Cheng Xin , Li Pei‐Zhi , Wang Guang , Yan Yu , Li Ke , Brand‐Saberi Beate , Yang Xuesong
Published: September 2018

Accumulating data show that the cytotoxicity of bacterial lipopolysaccharides (LPS) from microbiota or infection is associated with many disorders observed in the clinics. However, it is still obscure whether or not embryonic osteogenesis is affected by the LPS exposure during gestation. Using the early chicken embryo model, we could demonstrate that LPS exposure inhibits chondrogenesis of the 8‐day chicken embryos by Alcian Blue‐staining and osteogenesis of 17‐day by Alcian Blue and Alizarin Red staining. Further analysis of the growth plates showed that the length of the proliferating zone (PZ) increases whereas that of the hypertrophic zone (HZ) decreased following LPS exposure. However there is no significant change on cell proliferation in the growth plates. Immunofluorescent staining, western blot analysis, and quantitive polymerase chain reaction revealed that Sox9 and Col2a1 are highly expressed at the messenger RNA level and their protein products are also abundant. LPS exposure causes a downregulation of Runx2 and Col10a1 expression in 8‐day hindlimbs, and a suppression of Runx2, Col10a1, and Vegfa expression in 17‐day phalanges. Knocking down Sox9 in ATDC5 cells by small interfering RNA transfection lead to the expression reduction of Col2a1, Runx2, and Col10a1, implying the vital role of Sox9 in the process of LPS‐induced delay in the transition from proliferating chondrocytes to hypertrophic chondrocytes in the growth plate. In the presence of LPS, the antioxidant defense regulator nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is highly expressed, and the activities of superoxide dismutase 1 (SOD1), SOD2, and glutaredoxin rise in 17‐day phalanges and ADTC5 cells. Simultaneously, an increase of intracellular ROS is observed. When Nrf2 expression was knocked down in ATDC5 cells, the expressions of Sox9, Col2a1, Runx2, Col10a1, and Vegfa were also going down as well. Taken together, our current data suggest that LPS exposure during gestation could restrict the chondrocytes conversion from proliferating to hypertrophic in the growth plate, in which LPS‐induced Sox9 plays a crucial role to trigger the cascade of downstream genes by excessive ROS production and Nrf2 elevation.
Use of an in vitro dynamic culture system to assess flow shear forces upon cell adhesion within different structures
Authors: Hu Xingyou , Shen Gaotian , Hu Tao , Guan Guoping , Wang Lu
Published: September 2018

BACKGROUND

The perennial problems associated with long‐term patency of small diameter vascular grafts have yet to be satisfactorily resolved. One approach to rectify this problem is a rapid endothelialization on the inner wall of the grafts, which could significantly reduce inflammation or hyperplasia. Two critical factors that can affect this process in vivo include that of the biocompatibility of the materials and adhesion strength of cells on its surfaces. Thus, an important area of investigation involves an evaluation of cell adhesion on biomaterials in a dynamic culture system, but only limited research has been directed at examining the relationship between the shear forces resulting from flow rates and cell adhesion on the surface of materials. In this study, an in vitro dynamic culture system was utilized for use in examining such relationship by changing the flow rates.

RESULTS

Cells adherent on monofilaments were dislodged with a shear force of 5.4 dyn, while most cells adherent on multifilaments tolerated shear forces of 7.0 dyn.

CONCLUSION

Priority rankings of materials could be generated as a function of the shear forces tested, and the design or application of artificial blood vessel materials for use within specific regions of the body could be optimized. © 2018 Society of Chemical Industry
Evaporation‐induced self‐assembly (EISA) synthesized mesoporous bimetallic oxides (MBOs) enabling enhanced co‐uptake of arsenate and fluoride from water
Authors: Li Feihu , Fu Jingjing , Jin Jie , Wang Silan , Liu Yangyang , Yang Meng , Fu Xiaoru
Published: September 2018

BACKGROUND

Simultaneous removal of arsenic and fluoride anions from water by adsorption remains a challenge for environmental remediation practice. To address this issue, four mesoporous bimetallic oxides (MBOs) were prepared via the evaporation‐induced self‐assembly (EISA) method and studied as adsorbents for the co‐uptake of arsenate (As(V)) and fluoride (F−) from synthetic wastewater. Adsorption envelope and equilibrium experiments were performed to investigate the adsorption behaviors and properties.

RESULTS

These composites possessed high surface areas (e.g. 200 m2 g−1 for meso‐Ti/Al) and well‐defined mesopores, enabling high adsorption capacities for both As(V) and F−. The maximum adsorption capacities of mesoporous titanium‐lanthanum oxide (meso‐Ti/La) were as high as 81.42 mg g−1 and 44.37 mg g−1 for As(V) and F−, respectively. Surface complexation modeling indicates that As(V) removal mainly involved bidentate surface complexation with surface ≡Me‐OH, while F− was retained by formation of monodentate surface complexes.

CONCLUSION

The removal mechanisms were confirmed by X‐ray photoelectron spectroscopy. These MBOs were found to be effective for simultaneous removal of arsenic and fluoride from water. This study also demonstrated that the incorporation of multi‐components and mesoporosity into one composite is an efficient strategy for design and application of high‐efficiency adsorbents for environmental remediation of aqueous contaminants. © 2018 Society of Chemical Industry
The Appeal of Transformational Leadership
Authors: Hansbrough Tiffany Keller , Schyns Birgit
Published: September 2018

Although transformational leadership has been described as an ideal leadership style, there have been recent calls for research to examine why the concept of transformational leadership appeals to some individuals but not to others. Accordingly, three empirical studies were conducted to investigate the impact of personality and implicit leadership theories on the appeal of transformational leadership. The results indicate that conscientiousness strongly impacts the appeal of transformational leadership. Furthermore, the implicit leadership theory dimension of dedication mediates the relationship between conscientiousness and the appeal of transformational leadership. These findings thus question the universal appeal of transformational leadership as well as provide an explanatory mechanism regarding the differential appeal of transformational leadership.
pH‐dependent conformational dynamics of beta‐secretase 1: A molecular dynamics study
Authors: Mermelstein Daniel J. , McCammon J. Andrew , Walker Ross C.
Published: September 2018

Beta‐secretase 1 (BACE‐1) is an aspartyl protease implicated in the overproduction of β‐amyloid fibrils responsible for Alzheimer disease. The process of β‐amyloid genesis is known to be pH dependent, with an activity peak between solution pH of 3.5 and 5.5. We have studied the pH‐dependent dynamics of BACE‐1 to better understand the pH dependent mechanism. We have implemented support for graphics processor unit (GPU) accelerated constant pH molecular dynamics within the AMBER molecular dynamics software package and employed this to determine the relative population of different aspartyl dyad protonation states in the pH range of greatest β‐amyloid production, followed by conventional molecular dynamics to explore the differences among the various aspartyl dyad protonation states. We observed a difference in dynamics between double‐protonated, mono‐protonated, and double‐deprotonated states over the known pH range of higher activity. These differences include Tyr 71‐aspartyl dyad proximity and active water lifetime. This work indicates that Tyr 71 stabilizes catalytic water in the aspartyl dyad active site, enabling BACE‐1 activity.
Effects of bio‐based coatings on the ripening and quality attributes of tomato (Solanum lycopersicum) fruits
Authors: Aghofack‐Nguemezi Jean , Hoffmann Thomas , Schwab Wilfried
Published: September 2018

BACKGROUND

Postharvest conservation of tomatoes is a major current challenge for growers and traders. Edible coatings constitute a pertinent alternative to existing conservation methods.

RESULTS

Control tomatoes were fully ripe 3 days after harvesting, whereas fruits dipped in solutions containing extracts from cocoa pods (T1), cocoa leaves (T2) or coffee hulls (T3) reached full ripeness 14 days after treatment (DAT). Fruits treated by dipping in a solution containing an extract from coffee leaves (T4) were fully ripe 21 DAT. The visual assessment was confirmed by alterations in the level of chlorophyll a. Treatments induced a significant inhibition of chlorophyll a breakdown, especially during the first week after their application, T4 being the most efficacious. Weight loss increased significantly throughout the experimental period and was accelerated by treatments. Some quality‐related parameters of ripe tomato fruits were in most cases not significantly influenced by treatments. In a few cases, however, there were improvements in quality traits of ripe fruits. On 21 DAT, T4 induced significant increases in levels of β‐carotene and 6‐methyl‐3,5‐heptadien‐2‐ol, whereas T2 led, especially, to higher levels of volatile compounds.

CONCLUSION

Edible coatings based on extracts from coffee or cocoa leaves induced improvements in the shelf life and quality of tomato fruits. © 2018 Society of Chemical Industry
Science‐based regulatory approach for safe nutraceuticals
Authors: Sattigere Vijay D , Ramesh Kumar Parigi , Prakash Vish
Published: September 2018

Food safety is a very complex issue. The food that reaches the plate from the farm is exposed to many hazards in processing methods and each of those steps is likely to contribute, indirectly or directly, to contaminants and pathogens that ultimately make the food unsafe. Consumers would always wish for 100% product safety; even regulators want to ensure 100% safety of the product and protect consumers. Every country has its own food safety regulations, but the application of food safety management in the plant and prescription of standards with a clear network of organising the risk analysis in the chain is lacking. However, with the wide array of new health products – nutraceuticals, nutritional supplements, functional foods, dietary supplements, foods for special medical purposes and foods for special dietary uses – safety draws the attention consumers to a much greater extent. Foods may contain herb/plant or animal extracts that perhaps were not previously ingredients, making health claims a very challenging and difficult task for manufacturers and regulators in the food industry. This Mini‐Review attempts to address this issue from a science‐based viewpoint. © 2018 Society of Chemical Industry
Movement responses of roe deer to hunting risk
Authors: Picardi Simona , Basille Mathieu , Peters Wibke , Ponciano José Miguel , Boitani Luigi , Cagnacci Francesca
Published: September 2018

Large herbivores respond to fluctuations in predation and hunting risk. The temporal scale of risk heterogeneity affects behavioral responses and determines the usefulness of metrics to quantify them. We present a conceptual framework to link anti‐predator responses to risk fluctuations and appropriate metrics, based on temporal scale. We applied this framework to investigate movement responses of roe deer (Capreolus capreolus) to hunting risk, measured using movement rate and home range size. Because movements are also affected by reproductive phases, we considered potential effects of the rut in parallel to hunting risk. We compared movements of male and female roe deer in a protected site versus 2 hunted sites during and outside the hunting season and rut. We detected differences in movement rates in response to different hunting management practices. We did not detect effects for hunting regimes or between sexes during the rut when using home range size as the response variable. During the hunting season, movement rates were lower in the hunted sites than in the protected site, irrespective of sex. We did not observe differences in movement rates among sites outside of the hunting season. Males had higher movement rates than females during the rut in only 1 site. Our findings supported the hypothesis that roe deer decrease movements when exposed to high hunting risk. The effect of the rut on movements was negligible except for 1 study site. We suggest that movement rate is a more useful metric than home range size for assessing movement responses to hunting. © 2018 The Wildlife Society
Speech treatment in Parkinson's disease: Randomized controlled trial (RCT)
Authors: Ramig Lorraine , Halpern Angela , Spielman Jennifer , Fox Cynthia , Freeman Katherine
Published: September 2018

Background

As many as 89% of people with Parkinson's disease (PD) develop speech disorders.

Objectives

This randomized controlled trial evaluated two speech treatments for PD matched in intensive dosage and high‐effort mode of delivery, differing in subsystem target: voice (respiratory‐laryngeal) versus articulation (orofacial‐articulatory).

Methods

PD participants were randomized to 1‐month LSVT LOUD (voice), LSVT ARTIC (articulation), or UNTXPD (untreated) groups. Speech clinicians specializing in PD delivered treatment. Primary outcome was sound pressure level (SPL) in reading and spontaneous speech, and secondary outcome was participant‐reported Modified Communication Effectiveness Index (CETI‐M), evaluated at baseline, 1, and 7 months. Healthy controls were matched by age and sex.

Results

At baseline, the combined PD group (n = 64) was significantly worse than healthy controls (n = 20) for SPL (P < 0.05) and CETI‐M (P = 0.0001). At 1 and 7 months, SPL between‐group comparisons showed greater improvements for LSVT LOUD (n = 22) than LSVT ARTIC (n = 20; P < 0.05) and UNTXPD (n = 22; P < 0.05). Sound pressure level differences between LSVT ARTIC and UNTXPD at 1 and 7 months were not significant (P > 0.05). For CETI‐M, between‐group comparisons showed greater improvements for LSVT LOUD and LSVT ARTIC than UNTXPD at 1 month (P = 0.02; P = 0.02). At 7 months, CETI‐M between‐group differences were not significant (P = 0.08). Within‐group CETI‐M improvements for LSVT LOUD were maintained through 7 months (P = 0.0011).

Conclusions

LSVT LOUD showed greater improvements than both LSVT ARTIC and UNTXPD for SPL at 1 and 7 months. For CETI‐M, both LSVT LOUD and LSVT ARTIC improved at 1 month relative to UNTXPD. Only LSVT LOUD maintained CETI‐M improvements at 7 months. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
How significant is sub‐daily variability of rainfall for hydrological modelling of floods? A satellite based approach to sub‐daily downscaling of gauged rainfall
Authors: Shrestha Pallav K. , Shrestha Sangam , Ninsawat Sarawut
Published: September 2018

Floods exhibit pronounced sub‐daily variations originating from the rainfall variability during storm events. Accurate flood simulations require sub‐daily gauged rainfall which may not be available in all cases. This study evaluates an approach wherein daily gauged rainfall was downscaled to 3 hr resolution using the Tropical Rainfall Measurement Mission's (TRMM) 3B42 level 3 satellite rainfall product (Rsat). Hydrological performance of the TRMM downscaled rainfall (Rds) was compared with Rsat and daily gauged rainfall downscaled uniformly at 3 hr intervals (Runi) by forcing them individually into a pre‐calibrated distributed hydrological model. Satellite based sub‐daily downscaling of daily gauged rainfall (Rds) was witnessed to be the best alternative for flood analyses in the absence of sub‐daily measurements. Visual and statistical evaluation showed the superiority of Rds in flood hydrograph performance (hourly median values of Nash–Sutcliffe efficiency [NSE] 0.89 and R2 [co‐efficient of determination] 0.96) as well as in full‐length hydrograph performance (hourly overall values of NSE 0.72 and R2 0.69). Between Runi and Rsat, the choice rests on the purpose as the latter was more valuable for flood analysis while Runi was the better choice for achieving water balance and full‐length hydrograph match. The performance of Rds (good), Rsat (moderate) and Runi (poor) shows that a combination of rain gauge data downscaled with sub‐daily information from satellites provides the best option for accurate hydrological modelling of floods. Interestingly, Rds induced an additional lead error of 3.5 hr (median value) in flood peak timing which is recommended as a subject for future research.
Hemophilia B in a female with intellectual disability caused by a deletion of Xq26.3q28 encompassing the F9
Authors: Stoof Sara C. M. , Kersseboom Rogier , de Vries Femke A. T. , Kruip Marieke J. H. A. , Kievit Anneke J. A. , Leebeek Frank W. G.
Published: September 2018

Background

Hemophilia B is an X‐linked recessive disorder caused by mutations in the F9 on Xq27.1. Mainly males are affected but about 20% of female carriers have clotting factor IX activity below 0.40 IU/ml and bleeding problems. Fragile‐X syndrome (FMR1) and FRAXE syndrome (AFF2) are well‐known causes of X‐linked recessive intellectual disability. Simultaneous deletion of both FMR1 and AFF2 in males results in severe intellectual disability. In females the phenotype is more variable. We report a 19‐year‐old female with severe intellectual disability and a long‐standing bleeding history.

Methods

A SNP array analysis (Illumina Human Cyto 12‐SNP genotyping array) and sequencing of F9 were performed. Laboratory tests were performed to evaluate the bleeding diathesis.

Results

Our patient was diagnosed with mild hemophilia B after finding an 11 Mb deletion of Xq26.3q28 that included the following genes among others IDS, SOX3, FMR1, AFF2, and F9.

Conclusion

The case history demonstrates that a severe bleeding tendency suggestive of a hemostasis defect in patients with intellectual disability warrants careful hematological and genetic work‐up even in the absence of a positive family history.
On Darboux helices in Euclidean 4‐space
Authors: İlarslan Kazım , Yıldırım Mehmet
Published: September 2018

The notion of Darboux helix in Euclidean 3‐space was introduced and studied by Yaylı et al. 2012. They show that the class of Darboux helices coincide with the class of slant helices. In a special case, if the curvature functions satisfy the equality κ2 + τ2  =  constant, then these curves are curve of the constant precession.

In this paper, we study Darboux helices in Euclidean 4‐space, and we give a characterization for a curve to be a Darboux helix. We also prove that Darboux helices coincide with the general helices. In a special case, if the first and third curvatures of the curve are equal, then Darboux helix, general helix, and V4‐slant helix are the same concepts.
Nonstandard finite‐difference scheme to approximate the generalized Burgers‐Fisher equation
Authors: Namjoo Mehran , Zeinadini Mehdi , Zibaei Sadegh
Published: September 2018

In this paper, numerical solution of the generalized Burgers‐Fisher (BF) equation is presented on the basis of the nonstandard finite‐difference (NSFD) scheme. At first, two exact finite‐difference schemes for the BF equation are obtained. Afterwards, an NSFD scheme is presented for this equation. The positivity, consistency, and boundedness of the scheme are discussed. The numerical results obtained by the NSFD scheme is compared with the exact solution and some available methods to verify the accuracy and efficiency of the NSFD scheme.
Radial Nerve F‐wave reference values with surface electrodes from the anconeus muscle
Authors: Taga Arens , Poma Giuseppina , Cattaneo Luigi , Saccani Elena , Tinchelli Stefano , Pavesi Giovanni
Published: September 2018

Introduction: We sought to obtain normative values for radial nerve F‐wave variables, recording with surface electrodes from the anconeus muscle. Methods: We tested 30 healthy participants (17 women, 13 men) and measured the following variables: number of F waves/40 traces (F%); minimum, maximum, and mean F‐wave latency (FMIN, FMAX, FMED, respectively); F‐wave chronodispersion (FCHR); interside differences of F% and FMIN (DF% and DFMIN, respectively). Results: The mean F% was 41.3%; the normative values of FMIN, FMED, FMAX, and FCHR were < 21.2, <22.1, <23.3, and < 4.0 ms, respectively; and normative values of DF% and DFMIN were < 16.6% and < 1.1 ms, respectively. Height was the sole independent predictor in a regression model of FMIN, FMED, and FMAX; this explained 37%–44% of the variability. Discussion: We identified a feasible and useful technique to record radial nerve F waves from the anconeus muscle and obtained normative values of F‐wave variables. Muscle Nerve 59:244–246, 2019
Protective role of c‐Jun N‐terminal kinase‐2 (JNK2) in ibuprofen‐induced acute liver injury
Authors: Zoubek Miguel E , Woitok Marius M , Sydor Svenja , Nelson Leonard J , Bechmann Lars P , Lucena Maria I , Andrade Raul J , Bast Aalt , Koek Ger H , Trautwein Christian , Cubero Francisco J
Published: September 2018

Ibuprofen is a worldwide used non‐steroidal anti‐inflammatory drug which may cause acute liver injury (ALI) requiring liver transplantation. We aimed to unveil the molecular pathways involved in triggering ibuprofen‐induced ALI, which, at present, remain elusive. First, we investigated activation of essential pathways in human liver sections of ibuprofen‐induced ALI. Next, we assessed the cytotoxicity of ibuprofen in vitro and developed a novel murine model of ibuprofen intoxication. To assess the role of JNK, we used animals carrying constitutive deletion of c‐Jun N‐terminal kinase 1 (Jnk1−/−) or Jnk2 (Jnk2−/−) expression and included investigations using animals with hepatocyte‐specific Jnk deletion either genetically (Jnk1Δhepa) or by siRNA (siJnk2Δhepa). We found in human and murine samples of ibuprofen‐induced acute liver failure that JNK phosphorylation was increased in the cytoplasm of hepatocytes and other non‐liver parenchymal cells (non‐LPCs) compared with healthy tissue. In mice, ibuprofen intoxication resulted in a significantly stronger degree of liver injury compared with vehicle‐treated controls as evidenced by serum transaminases, and hepatic histopathology. Next, we investigated molecular pathways. PKCα, AKT, JNK and RIPK1 were significantly increased 8 h after ibuprofen intoxication. Constitutive Jnk1−/− and Jnk2−/− deficient mice exhibited increased liver dysfunction compared to wild‐type (WT) animals. Furthermore, siJnk2Δhepa animals showed a dramatic increase in biochemical markers of liver function, which correlated with significantly higher serum liver enzymes and worsened liver histology, and MAPK activation compared to Jnk1Δhepa or WT animals. In our study, cytoplasmic JNK activation in hepatocytes and other non‐LPCs is a hallmark of human and murine ibuprofen‐induced ALI. Functional in vivo analysis demonstrated a protective role of hepatocyte‐specific Jnk2 during ibuprofen ALI. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Comparing outpatient oral antibiotic use in Germany and the Netherlands from 2012 to 2016
Authors: Gradl Gabriele , Teichert Martina , Kieble Marita , Werning Johanna , Schulz Martin
Published: September 2018

Purpose

Overuse of antibiotics is of concern, but may differ between European countries. This study compares outpatient use of oral antibiotics between Germany (DE) and the Netherlands (NL).

Methods

For DE, we used the DAPI database with information on dispensings at the expense of the Statutory Health Insurance Funds from > 80% of community pharmacies. For NL, data were obtained from the Dutch Foundation for Pharmaceutical Statistics. Use of oral antibiotics was estimated as defined daily doses per 1000 inhabitants per day (DID), except for age comparisons as packages per 1000 inhabitants annually. National time trends were assessed with linear regression, stratified for the major antibiotic classes, and individual substances.

Results

From 2012 to 2016, outpatient antibiotic use was lower in NL than in DE (9.64 vs 14.14 DID in 2016) and non‐significantly decreased slightly over time in both countries. In DE, dispensings of oral antibiotics to children were higher compared with NL for the age groups 2 to 5 (2.0‐fold in 2016) and 6 to 14 years (2.7‐fold in 2016). Use of cephalosporins was very low in NL (0.02 DID in 2016), but the second most frequently dispensed class in DE (2.95 DID in 2016).

Conclusion

From 2012 to 2016, outpatient use of oral antibiotics was lower in NL than in DE. Differences were primarily observed in the age groups 2 to 5 and 6 to 14 years, although the recommendations of evidence‐based guidelines in both countries were in agreement.
Exposure measurement error when assessing current glucocorticoid use using UK primary care electronic prescription data
Authors: Joseph Rebecca M. , van Staa Tjeerd P. , Lunt Mark , Abrahamowicz Michal , Dixon William G.
Published: September 2018

Purpose

To quantify misclassification in glucocorticoid (GC) exposure defined using UK primary care prescription data.

Methods

A cross‐sectional study including patients with rheumatoid arthritis prescribed oral GCs in the past 2 years. Glucocorticoid exposure based on electronic prescription records was compared with participant‐reported GC use captured using a paper diary. Prescription data (containing information about prescriptions issued but no dispensing information) was provided by the Clinical Practice Research Datalink. The following variables were defined: current use and dose of oral GCs and if (and when) participants had received a GC injection. For oral GCs, self‐reported use was taken to represent “true” exposure. A dataset representing a hypothetical population was generated to assess the impact of the misclassification found for current use.

Results

A total of 67 of 78 study participants (86%) were correctly classified as currently on/off oral GCs; 32/38 (84.2%) participants reporting current GC use and 35/40 (87.5%) participants not reporting current use were correctly classified. Estimated values of current dose were imprecise (correlation coefficient 0.46). Concordance between reported and prescribed GC injections was poor (kappa statistic 0.14). Misclassification bias was demonstrated in the hypothetical population: For “true” relative risks of 1.5, 4, and 9, the “observed” relative risks were 1.33, 2.48, and 3.58, respectively.

Conclusions

Misclassification of current use of oral GCs was low but sufficient to lead to significant bias. Researchers should take care to assess the likely impact of exposure misclassification on their analyses.