bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracking CO Release in Cells via the Luminescence of Donor Molecules and/or their By‐Products
Authors: Soboleva Tatiana , Berreau Lisa M.
Published: February 2019

Carbon monoxide (CO) is a bioactive signalling molecule that is produced endogenously via the breakdown of heme. Beneficial health effects associated with the delivery of CO gas have spurred the development of CO‐releasing molecules (CORMs) that can be used to provide specific amounts of the gas. In addition to their potential use as therapeutics, CORMs are needed to provide insight into the biological targets of CO. In this regard, light‐activated CO‐releasing molecules (photoCORMs), are valuable for examining the effects of localized CO release.

Herein we examine luminescent CORMs and photoCORMs that have been reported for tracking CO delivery in cells. A variety of motifs are available that exhibit differing luminescence properties and cover a wide range of wavelengths. Trackable CO donors have been successfully applied to targeting CO delivery to mitochondria, thus demonstrating the feasibility of using such molecules in detailed investigations of the biological roles of CO.
Acute kidney injury model established by systemic glutathione depletion in mice
Authors: Matsubara Akiko , Oda Shingo , Jia Ru , Yokoi Tsuyoshi
Published: February 2019

Glutathione (GSH) is one of the most extensively studied tripeptides. The roles for GSH in redox signaling, detoxification of xenobiotics and antioxidant defense have been investigated. A drug‐induced rhabdomyolysis mouse model was recently established in L‐buthionine‐(S,R)‐sulfoximine (BSO; a GSH synthesis inhibitor)‐treated normal mice by co‐administration of antibacterial drug and statin. In these models, mild kidney injury was observed in the BSO only‐treated mice. Therefore, in this study, we studied kidney injury in the GSH‐depleted mouse. BSO was intraperitoneally administered twice a day for 7 days to normal mice. The maximum level of plasma creatine phosphokinase (351 487 ± 53 815 U/L) was shown on day 8, and that of aspartate aminotransferase was shown on day 6. Increased levels of blood urea nitrogen, plasma creatinine, urinary kidney injury molecule‐1 and urinary creatinine were observed. An increase of mRNA expression level of renal lipocalin 2/neutrophil gelatinase‐associated lipocalin was observed. Degeneration and necrosis in the skeletal muscle and high concentrations of myoglobin (Mb) in blood (347‐203 925 ng/mL) and urine (2.5‐68 583 ng/mL) with large interindividual variability were shown from day 5 of BSO administration. Mb‐stained regions in the renal tubule and renal cast were histologically observed. In this study, the GSH‐depletion treatment established an acute kidney injury mouse model due to Mb release from the damaged skeletal muscle. This mouse model would be useful for predicting potential acute kidney injury risks in non‐clinical drug development.
Electrospun triple‐layered PLLA/gelatin. PRGF/PLLA scaffold induces fibroblast migration
Authors: Piran Mehrdad , Shiri Mahdi , Soufi Zomorrod Mahsa , Esmaeili Elaheh , Soufi Zomorrod Mina , Vazifeh Shiran Nader , Mahboudi Hossein , Daneshpazhouh Hamed , Dehghani Naeimeh , Hosseinzadeh Simzar
Published: February 2019

The function of fibroblast cells in wounded areas results in reconstruction of the extra cellular matrix and consequently resolution of granulation tissue. It is suggested that the use of platelet‐rich plasma can accelerate the healing process in nonhealing or slow‐healing wounds. In this study, a simple and novel method has been used to fabricate an electrospun three‐layered scaffold containing plasma rich in growth factor with the aim of increasing the proliferation and migration of fibroblast cells in vitro. First, plasma rich in growth factor was derived from platelet rich plasma, and then a three‐layered scaffold was fabricated using PLLA nanofibers as the outer layers and plasma rich in growth factor‐containing gelatin fibers as the internal layer. The growth morphology of cells seeded on this scaffold was compared to those seeded on one layered PLLA scaffold. The study of the cell growth rate on different substrates and the migration of cells in response to the drug release of multilayered scaffold was investigated by the cell quantification assay and a modified under agarose assay. Scanning electron microscopy and fluorescence images showed that cells seeded on multilayered scaffold were completely oriented 72 hours after seeding compared to those seeded on PLLA scaffold. The cell quantification assay also indicated significant increase in proliferation rate of cells seeded on three‐layered scaffold compared to those seeded on PLLA scaffold and finally, monitoring cell migration proved that cells migrate significantly toward the three‐layered scaffold up to 48 to 72 hours and afterwards start to show a diminished migration rate toward this scaffold.
Elevated expression of the V‐ATPase D2 subunit triggers increased energy metabolite levels in KrasG12D‐driven cancer cells
Authors: Yang Jigang , Guo Feihu , Yuan Leilei , Lv Guangxin , Gong Jianhua , Chen Jing
Published: February 2019

Mutations of the Ras oncogene are frequently detected in human cancers. Among Ras‐mediated tumorigenesis, Kras‐driven cancers are the most dominant mutation types. Here, we investigated molecular markers related to the Kras mutation, which is involved in energy metabolism in Kras mutant‐driven cancer. We first generated a knock‐in KrasG12D cell line as a model. The genotype and phenotype of the Kras
G12D‐driven cells were first confirmed. Dramatically elevated metabolite characterization was observed in Kras
G12D‐driven cells compared with wild‐type cells. Analysis of mitochondrial metabolite‐related genes showed that two of the 84 genes in Kras
G12D‐driven cells differed from control cells by at least twofold. The messenger RNA and protein levels of ATP6V0D2 were significantly upregulated in Kras
G12D‐driven cells. Knockdown of ATP6V0D2 expression inhibited motility and invasion but did not affect the proliferation of Kras
G12D‐driven cells. We further investigated ATP6V0D2 expression in tumor tissue microarrays. ATP6V0D2 overexpression was observed in most carcinoma tissues, such as melanoma, pancreas, and kidney. Thus, we suggest that ATP6V0D2, as one of the V‐ATPase (vacuolar‐type H
+‐ATPase) subunit isoforms, may be a potential therapeutic target for Kras mutation cancer.
Molecular interaction of investigational ligands with human brain acetylcholinesterase
Authors: Shakil Shazi
Published: February 2019

Alzheimer's disease, a neurodegenerative disorder continues to be an area of investigation by the international researchers’ fraternity. Despite all the ongoing efforts, the effective set of promising cholinesterase inhibitors available in the market for patients’ use is limited. Furthermore, the currently available drugs could provide only a palliative type of treatment instead of providing a complete cure or foolproof prevention. Hence, design/discovery of fresh drug molecules as acetylcholinesterase (AChE) inhibitors still remains an urgent requirement. The drug discovery platform, MCULE in the “structure‐based virtual screening” (SBVS) mode was used for high throughput ligand screening of over five million structures targeted against the AChE catalytic site. A stepwise query was made for the SBVS input. The number of hits was narrowed down in consecutive succession via varied filtration criteria as AutoDock‐Vina rankings, MCULE toxicity filtration, exclusion of ligands having less than four H‐bond acceptors, filtration by ΔG cutoff, rule‐of‐five violation and SWISS ADME profiling. This was followed by holistic analysis of all the results, thereby leading to one promising ligand. The screened out drug molecule, MCULE‐5872671137‐0‐1 exhibited a robust interaction with the AChE catalytic site involving 20 amino acid residues, an acceptable binding free energy of −10.2 kcal/mol in addition to a favorable SWISS ADME‐profie showing no harmful effects on the human body. It can be carefully stated that the molecule, MCULE‐5872671137‐0‐1, which is chemically (3S)‐N‐{4‐[(4‐chlorophenyl)sulfanyl]phenyl}‐3‐hydroxypyrrolidine‐1‐carboxamide could function as a significant “seed” ligand for future design of potent AChE inhibitors and/or novel neuro drugs built upon the seed‐scaffold.
Continuous enantiomer‐selective acylation reaction of 1‐phenylethanamine in a magnetic fluidized bed reactor system (MFBRS)
Authors: Ou Zhimin , Pan Jiaying , Tang Lan , Shi Hanbing
Published: February 2019

BACKGROUND

Magnetic nanoparticle immobilized enzymes are attractive owing to their potential applications in many biological fields. When an alternating magnetic field is applied, the magnetic moments of the magnetic nanoparticles are apt to align in the direction of the field, and the magnetic nanoparticles experience force in the direction of the field. Thus, the magnetic nanoparticles behave like microscopic stirrers.

RESULTS

In this study, (R)‐N‐(1‐phenylethyl)acetamide was prepared continuously using immobilized lipase in an alternating magnetic field. The effect of several factors on the acylation reaction were investigated. A kinetic model of the continuous acylation reaction process also was developed. The conversion of 1‐phenylethanamine reached a maximum value of 41.8% with lipase concentration 75 mg mL−1 (dry weight/reaction volume), substrate concentration 500 mmol L−1 and flow rate 25 μL min−1 The enantiomeric excess of (R)‐N‐(1‐phenylethyl)acetamide was > 98.4%. The kinetic constants of the continuous reduction were rm = 2.25 × 10−2 mmol L–1 min−1, kcat = 6 × 10−4 mmol L–1 min−1, KA = 0.75 mmol L–1 , KB = 4.36 × 10−3, KQA = 2.43 × 10−2 and KBQA = 6.2 × 10−4 mmol L–1. The kinetic model was in good agreement with the experimental data obtained during continuous acylation reaction.

CONCLUSION

The results revealed that the inhibition of the acylation reaction at high substrate concentrations was eliminated during the continuous reaction. Compared with the batch acylation reaction, the continuous acylation reaction showed significantly improved lipase catalyst efficiency. © 2019 Society of Chemical Industry
Beyond inference by eye: Statistical and graphing practices in JEAB, 1992‐2017
Authors: Kyonka Elizabeth G. E. , Mitchell Suzanne H. , Bizo Lewis A.
Published: February 2019

Debates about the utility of p values and correct ways to analyze data have inspired new guidelines on statistical inference by the American Psychological Association (APA) and changes in the way results are reported in other scientific journals, but their impact on the Journal of the Experimental Analysis of Behavior (JEAB) has not previously been evaluated. A content analysis of empirical articles published in JEAB between 1992 and 2017 investigated whether statistical and graphing practices changed during that time period. The likelihood that a JEAB article reported a null hypothesis significance test, included a confidence interval, or depicted at least one figure with error bars has increased over time. Features of graphs in JEAB, including the proportion depicting single‐subject data, have not changed systematically during the same period. Statistics and graphing trends in JEAB largely paralleled those in mainstream psychology journals, but there was no evidence that changes to APA style had any direct impact on JEAB. In the future, the onus will continue to be on authors, reviewers and editors to ensure that statistical and graphing practices in JEAB continue to evolve without interfering with characteristics that set the journal apart from other scientific journals.
Detoxification and functionalization of gold nanorods with organic polymers and their applications in cancer photothermal therapy
Authors: Jin Na , Zhang Qing , Yang Manyi , Yang Mingying
Published: February 2019

Gold nanorods (AuNRs) have attracted widespread attention in the last few decades due to their potential applications in cancer photothermal therapy (CPTT). However, the utilization of AuNRs is restricted because of their high toxicity for cells and tissues. Numerous methods have been developed to solve this problem, among which the most convenient one is to coat AuNRs with biocompatible materials or replace their original toxic surfactant such as the hexadecyl‐trimethyl ammonium bromide (CTAB). Organic polymers (OPs) are intensively researched due to their low toxicity and easy access to modification with functional groups (e.g.,targeting molecules), pharmaceuticals (e.g.,chemo drugs) and imaging agents (e.g.,radioactive elements). Herein, this mini review summarized recent progress in detoxification and functionalization of AuNRs exploiting OPs coatings and their applications in CPTT. To begin with, we introduced current major approaches used to modify AuNRs with typical OPs. Then, applications of OPs coated AuNRs in CPTT were discussed. At the end of the review, we proposed a brief outlook for the future development of modification and functionalization of AuNRs with organic materials.
Feature enhancement framework for brain tumor segmentation and classification
Authors: Tahir Bilal , Iqbal Sajid , Usman Ghani Khan M. , Saba Tanzila , Mehmood Zahid , Anjum Adeel , Mahmood Toqeer
Published: February 2019

Automatic medical image analysis is one of the key tasks being used by the medical community for disease diagnosis and treatment planning. Statistical methods are the major algorithms used and consist of few steps including preprocessing, feature extraction, segmentation, and classification. Performance of such statistical methods is an important factor for their successful adaptation. The results of these algorithms depend on the quality of images fed to the processing pipeline: better the images, higher the results. Preprocessing is the pipeline phase that attempts to improve the quality of images before applying the chosen statistical method. In this work, popular preprocessing techniques are investigated from different perspectives where these preprocessing techniques are grouped into three main categories: noise removal, contrast enhancement, and edge detection. All possible combinations of these techniques are formed and applied on different image sets which are then passed to a predefined pipeline of feature extraction, segmentation, and classification. Classification results are calculated using three different measures: accuracy, sensitivity, and specificity while segmentation results are calculated using dice similarity score. Statistics of five high scoring combinations are reported for each data set. Experimental results show that application of proper preprocessing techniques could improve the classification and segmentation results to a greater extent. However, the combinations of these techniques depend on the characteristics and type of data set used.
Synthesis, Antimicrobial, and Antioxidant Screening of Aryl Acetic Acid Incorporated 1,2,4‐Triazolo‐1,3,4‐Thiadiazole Derivatives
Authors: Kamboj Vipan Kumar , Kapoor Archana , Jain Sandeep
Published: February 2019

Some novel [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole derivatives were synthesized from aryl acetic acids. All the synthesized derivatives were selected for the screening of antibacterial potential against Gram‐positive bacteria [Staphylococcus aureus (MTCC 3160) and Micrococcus luteus (MTCC 1538)] and Gram‐negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)] and antifungal potential against Aspergillus niger (MTCC 8652) and Candida albicans (MTCC 227), and free radical scavenging activity through 2,2‐diphenyl‐2‐picrylhydrazyl hydrate method. The compounds TH‐4, TH‐13, and TH‐19 were found to be more potent antimicrobial agents compared to standard drugs. The compounds TH‐3, TH‐9, and TH‐18 also showed significant antimicrobial activity. The compound TH‐13 showed antioxidant activity with IC50 value better than the standard compound. The structures of all the synthesized compounds were confirmed by Fourier transform infrared, 1H‐NMR, liquid chromatography–mass spectrometry, and CHN analyzer.
Weights for general circulation models from CMIP3/CMIP5 in a statistical downscaling framework and the impact on future Mediterranean precipitation
Authors: Kaspar‐Ott Irena , Hertig Elke , Kaspar Severin , Pollinger Felix , Ring Christoph , Paeth Heiko , Jacobeit Jucundus
Published: February 2019

This study investigates the projected precipitation changes of the 21st century in the Mediterranean area with a model ensemble of all available CMIP3 and CMIP5 data based on four different scenarios. The large spread of simulated precipitation change signals underlines the need of an evaluation of the individual general circulation models in order to give higher weights to better and lower weights to worse performing models. The models' spread comprises part of the internal climate variability, but is also due to the differing skills of the circulation models. The uncertainty resulting from the latter is the aim of our weighting approach. Each weight is based on the skill to simulate key predictor variables in context of large and medium scale atmospheric circulation patterns within a statistical downscaling framework for the Mediterranean precipitation. Therefore, geopotential heights, sea level pressure, atmospheric layer thickness, horizontal wind components and humidity data at several atmospheric levels are considered. The novelty of this metric consists in avoiding the use of the precipitation data by itself for the weighting process, as state‐of‐the‐art models still have major deficits in simulating precipitation. The application of the weights on the downscaled precipitation changes leads to more reliable and precise change signals in some Mediterranean sub‐regions and seasons. The model weights differ between sub‐regions and seasons, however, a clear sequence from better to worse models for the representation of precipitation in the Mediterranean area becomes apparent.
Use of Concentrated Parenteral Nutrition Solutions Is Associated With Improved Nutrient Intakes and Postnatal Growth in Very Low‐Birth‐Weight Infants
Authors: Späth Cornelia , Zamir Itay , Sjöström Elisabeth Stoltz , Domellöf Magnus
Published: February 2019

Background

Evidence showing the beneficial effects of enhanced parenteral nutrition (PN) to very low‐birth‐weight (VLBW, <1500 g) infants is accumulating. However, PN composition and its impact on growth outcomes are questioned. This study aimed to investigate the associations between administration of a concentrated PN regime and intakes of energy and macronutrients as well as postnatal growth in VLBW infants.

Methods

We compared 2 cohorts of VLBW infants born before (n = 74) and after (n = 44) a concentrated PN regime was introduced into clinical use. Daily nutrition and fluid intake during the first 28 postnatal days and all available growth measurements during hospitalization were retrospectively collected from clinical charts.

Results

Infants who received concentrated PN compared with original PN had higher parenteral intakes of energy (56 vs 45 kcal/kg/d,P< 0.001), protein (2.6 vs 2.2 g/kg/d,P= 0.008), and fat (1.5 vs 0.7 g/kg/d,P< 0.001) during the first postnatal week. Changes in standard deviation scores for weight and length from birth to postnatal day 28 were more positive in the concentrated PN group (mean [95% CI]; weight change: –0.77 [–1.02 to –0.52] vs –1.29 [–1.33 to –1.05],P= 0.005; length change: –1.01 [–1.36 to –0.65] vs –1.60 [–1.95 to –1.25],P= 0.025). There were no significant differences in fluid intake and infant morbidity between the groups.

Conclusion

Our results suggest that concentrated PN is useful and seems to be safe for improving early nutrition and growth in VLBW infants.
The power of odour volatiles from unifloral melipona honey evaluated by gas chromatography–olfactometry Osme techniques
Authors: Costa Ana CV , Garruti Deborah S , Madruga Marta S
Published: February 2019

Background

The quality and power of each odorous volatile present in the headspace of unifloral honey velame branco (Croton heliotropiifolius Kunth) prepared by stingless uruçu (Melipona scutellaris Latrelle) were evaluated using the gas chromatography–olfactometry Osme technique. Five trained panellists evaluated the sensory chromatographic effluent in three replications, and the results were integrated by SCDTI software.

Results

Of the 42 compounds identified in the chromatogram, 17 odorous stimuli were detected by the sensory panel. Among these compounds, the most odoriferous impacts were pentanoate acetate ‘ripe fruit’, safranal green, medicinal plant and methyl eugenol ‘clove, tea’. The furaneol compounds, hotrienol and benzaldehyde showed aroma notes associated with honey.

Conclusion

These results are important since, in addition to revealing the presence of compounds that are not identified by other analytical methods, they can also assist in the verification of monofloral honeys compliance. © 2019 Society of Chemical Industry
Modeling precursors of impulsive tourist shopping behavior: Evidence from long‐haul Chinese outbound tourists
Authors: Meng Fang , Zhang Pei , Li Hengyun , So Kevin Kam Fung
Published: February 2019

Studies have examined tourism shopping in various aspects, but scarce research has specifically focused on impulsive shopping behavior of tourists, which is of particular relevance in the tourism settings. This study addresses this paucity by examining factors influencing impulsive tourist shopping urge and purchase from the aspects of tourist internal attribute, social influence, and product attribute. By examining Chinese long‐haul tourists traveled outside Asia, the empirical results suggest that (a) impulsive trait and hedonic and materialistic tendency of tourists lead to impulsive urge and engagement in actual impulsive buying; (b) shopping companion/social influences from family and relatives, peers (friends/colleagues), and shop assistants also affect the impulsive shopping urge; (c) product brand variety shows significant effect on impulsive urge, whereas the influence of product price is insignificant; and (d) traveling with a shopping list or not moderates the relationship between impulsive urge and actual impulsive purchase. The study advances the theoretical understanding of tourist impulsive shopping behavior and provides marketing/managerial insights into Chinese overseas tourism market.
Long‐Term Measures of Dyslipidemia, Inflammation, and Oxidative Stress in Rats Fed a High‐Fat/High‐Fructose Diet
Authors: Feillet‐Coudray Christine , Fouret Gilles , Vigor Claire , Bonafos Béatrice , Jover Bernard , Blachnio‐Zabielska Agnieszka , Rieusset Jennifer , Casas François , Gaillet Sylvie , Landrier Jean Francois , Durand Thierry , Coudray Charles
Published: February 2019

Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy‐five male Wistar rats were divided to control and high‐fat high‐fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr‐fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL‐6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid‐reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies.
Characterization of Collagen/Lipid Nanoparticle–Curcumin Cryostructurates for Wound Healing Applications
Authors: Laghezza Masci Valentina , Taddei Anna‐Rita , Courant Thomas , Tezgel Ozgül , Navarro Fabrice , Giorgi Franco , Mariolle Denis , Fausto Anna‐Maria , Texier Isabelle
Published: February 2019

Curcumin‐loaded collagen cryostructurates have been devised for wound healing applications. Curcumin displays strong antioxidant, antiseptic, and anti‐inflammatory properties, while collagen is acknowledged for promoting cell adhesion, migration and differentiation. However, when curcumin is loaded directly into collagen hydrogels, it forms large molecular aggregates and clogs the matrix pores. A double‐encapsulation strategy is therefore developed by loading curcumin into lipid nanoparticles (LNP), and embedding these particles inside collagen scaffolds. The resulting collagen/LNP cryostructurates have an optimal fibrous structure with ≈100 µm average pore size for sustaining cell migration. Results show that collagen is structurally unaltered and that nanoparticles are homogeneously distributed amidst collagen fibers. Hydrogels soaked in saline buffer release about 20 to 30% of their nanoparticles content within 24 h, while achieved 100% release after 25 days. When exposed to NIH 3T3 fibroblasts, these hydrogels provide a satisfactory scaffold for cell interaction as early as 4 h after seeding, with no cytotoxic counter effect. These positive features make the collagen/lipid cryostructurates a promising material for further use in wound healing.
Blends of Polystyrene/Shoes Waste (SBRr): Influence of Mixture Sequence and Compatibilizer
Authors: Luna Carlos Bruno B. , da Silva Divânia F. , Araújo Edcleide M. , de Mélo Tomás Jeferson A. , de Oliveira T. Bezerra Ewerton , Siqueira Danilo D. , de Oliveira Amanda D.
Published: February 2019

The aim of this research is to analyze the influence of the mixture sequence and compatibilizer on the morphology and mechanical and thermomechanical properties of polystyrene (PS)/shoes waste (SBRr) blends. The blends are processed in a twin screw co‐rotating extruder and then injection molded. They are analyzed by impact and tensile tests, Shore D hardness, heat deflection temperature (HDT), ductile‐brittle transition temperature and transmission electron microscopy (TEM). The results showed that there is a significant increase in the impact strength, in the hardness and in the HDT of the blends when PS and styrene–butadiene–styrene (SBS) were mixed together in a first extrusion, prior to the incorporation of the SBRr into a second extrusion. However, the different mixing sequences studied apparently did not influence the results of tensile strength. The morphology showed by the mixing sequence (PS/SBS) + SBRr evidenced a better dispersion of the SBRr in the PS matrix, favoring better properties.
A compartmental model for global spread dynamics of malware under mutation
Authors: Ren Jianguo , Xu Yonghong , Xie Chunli , He Shouwu
Published: February 2019

Malware mutation is pervasive among networks. Modeling and understanding its propagation characteristics have been of great importance. In this study, a new compartmental model that extends the present model by incorporating mutated malware into the modeling process as a separate dynamic variable is proposed and theoretically analyzed to deepen the understanding of the spreading mechanisms of mutated malware. The model involves two equilibria, namely, malware‐free equilibrium and malware equilibrium, wherein both have proven to be locally and globally asymptotically stable through the Routh‐Hurwitz criterion and Lyapunov functional approach, respectively. An epidemic threshold is obtained that clearly forms the boundary among the comprehensive dynamics of the model between two distinct ramifications: one with mutation infection prevalence and the other without any mutation infection. Both are incarnated via the existence and stability of the equilibria admitted by the model. Further analyses show that the mutation is related not only to the epidemic threshold, but also to the malware prevalence level. The numerical simulations based on the analytic results demonstrate that the diffusion of mutated malware can fall away or can be maintained at a suitable level.
A monolithic approach to fluid‐structure interaction based on a hybrid Eulerian‐ALE fluid domain decomposition involving cut elements
Authors: Schott B. , Ager C. , Wall W.A.
Published: February 2019

A novel method for complex fluid‐structure interaction (FSI) involving large structural deformation and motion is proposed. The new approach is based on a hybrid fluid formulation that combines the advantages of purely Eulerian (fixed‐grid) and arbitrary Lagrangian‐Eulerian (ALE) moving mesh formulations in the context of FSI. The structure, as commonly given in Lagrangian description, is surrounded by a fine resolved layer of fluid elements based on an ALE‐framework. This ALE‐fluid patch, which is embedded in a Eulerian background fluid domain, follows the deformation and motion of the structural interface. This approximation technique is not limited to finite element methods but can also be realized within other frameworks like finite volume or discontinuous Galerkin methods. In this work, the surface coupling between the two disjoint fluid subdomains is imposed weakly using a stabilized Nitsche's technique in a cut finite element method (CutFEM) framework. At the fluid‐solid interface, standard weak coupling of node‐matching or nonmatching finite element approximations can be utilized. As the fluid subdomains can be meshed independently, a sufficient mesh quality in the vicinity of the common fluid‐structure interface can be assured. To our knowledge, the proposed method is the only method (despite some overlapping domain decomposition approaches that suffer from other issues) that allows for capturing boundary layers and flow detachment via appropriate grids around largely moving and deforming bodies. In contrast to other methods, it is possible to do this, eg, without the necessity of costly remeshing procedures. A clear advantage over existing overlapping domain decomposition methods consists in the sharp splitting of the fluid domain, which comes along with improved convergence behavior of the resulting monolithic FSI system. In addition, it might also help to save computational costs as now background grids can be much coarser. Various FSI‐cases of rising complexity conclude the work. For validation purpose, results have been compared to simulations using a classical ALE‐fluid description or purely fixed‐grid CutFEM‐based schemes.
Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis
Authors: Toney Ashley Mulcahy , Fan Rong , Xian Yibo , Chaidez Virginia , Ramer‐Tait Amanda E. , Chung Soonkyu
Published: February 2019

Objective

Urolithin A (UroA) is a major metabolite of ellagic acid produced following microbial catabolism in the gut. Emerging evidence has suggested that UroA modulates energy metabolism in various cells. However, UroA’s physiological functions related to obesity and insulin resistance remain unclear.

Methods

Male mice were intraperitoneally administrated either UroA or dimethyl sulfoxide (vehicle) along with a high‐fat diet for 12 weeks. Insulin sensitivity was evaluated via glucose and insulin tolerance tests and acute insulin signaling. The effects of UroA on hepatic triglyceride accumulation, adipocyte size, mitochondrial DNA content, and proinflammatory gene expressions were determined. The impact of UroA on macrophage polarization and mitochondrial respiration were assessed in bone marrow–derived macrophages.

Results

Administration of UroA (1) improved systemic insulin sensitivity, (2) attenuated triglyceride accumulation and elevated mitochondrial biogenesis in the liver, (3) reduced adipocyte hypertrophy and macrophage infiltration into the adipose tissue, and (4) altered M1/M2 polarization in peritoneal macrophages. In addition, UroA favored macrophage M2 polarization and mitochondrial respiration in bone marrow‐derived macrophages.

Conclusions

UroA plays a direct role in improving systemic insulin sensitivity independent of its parental compounds. This work supports UroA’s role in the metabolic benefits of ellagic acid–rich foods and highlights the significance of its microbial transformation in the gut.
Ring‐Stacking Water Clusters: Morphology and Stabilities
Authors: Yang Liu , Ji Hanyang , Liu Xiaojie , Lu Wen‐Cai
Published: February 2019

The structures and interaction energies of water clusters with ring stacking motifs are studied by using ab initio calculations. The structures of the water clusters are constructed by stacking either single rings or multi‐rings of tetramer, pentamer, and hexamer. We found that, in the single‐ring‐stacking motif, the most stable isomers exhibit an alternative clockwise‐anticlockwise stacking pattern. We also show that four‐layer single‐ring‐stacking isomers are not energetically favorable in comparison with those of two‐layer multi‐ring‐stacking isomers. The relative stability of the isomers is also analyzed in terms of H‐bond strength and elastic distortions of the water molecules.
Weakening of mechanical properties of cellulose separator caused by electrolyte immersion and elevated temperature
Authors: Liu Wangyu , Dang Yanping , Xie Weigui , Tang Aimin
Published: February 2019

The separator is an important component of the lithium‐ion batteries (LIBs). Considering the influence of temperature and hygroexpansion effect of cellulose materials, the mechanical properties of cellulose separators in air (dry), electrolyte immersion (wet), and elevated temperature (heated) environments are studied. Firstly, orthogonal experiments were designed and conducted to investigate the effects of various factors on the tensile properties of cellulose separators. Based on the results of the orthogonal test, the cellulose separator and the polypropylene (PP) separator were then subjected to tensile and puncture test under dry and wet condition, respectively. The results show that temperature has slight effect on cellulose separator, while it is known that PP separator has weak thermal stability. The mechanical property of PP separator is not sensitive to the immersion of electrolyte. However, the mechanical strength of cellulose separator is greatly reduced when immersed in electrolyte or exposed to high temperature. The tensile property and puncture property of the cellulose separator are severely decreased in the electrolyte. The mechanical properties of the cellulose separator in the electrolyte are insufficient to ensure battery safety. The hydro‐thermal properties of cellulose separator need enhancement in the future research. POLYM. COMPOS., 40:3857–3865, 2019. © 2019 Society of Plastics Engineers
Properties and Structure of ADN‐Prills
Authors: Heintz Thomas , Herrmann Michael J.
Published: February 2019

Ammonium dinitramide (ADN) is the upcoming oxidizer for solid propellants of the current decade. Spherical ADN particles, so‐called ADN‐prills, are a key product for the development of environmentally friendly and low‐signature solid propellants for defence and space applications. At the moment the particle size and the spherical shape of the ADN‐prills can be controlled by the emulsion crystallization process or by spray congealing processes. In this work the crystal structure and the thermal‐ and mechanical stability of ADN‐prills were investigated. By temperature resolved X‐ray diffraction measurements new insights about temperature depending crystalline structures inside of ADN‐prills could be gained. Anisotropic crystal properties could be detected at certain temperature ranges between ambient temperature and the melting point of ADN at 93 °C. Due to the unexpected material properties of molten ADN droplets a surprising correlation between process parameters, particle size, crystal structure, thermal stability and mechanical stability was found. This leads to a more profound knowledge about the crystal structure of ADN‐prills and gives the opportunity to produce enhanced ADN particles for propellant applications.
Peptide‐based building blocks as structural elements for supramolecular Gd‐containing MRI contrast agents
Authors: Diaferia Carlo , Gianolio Eliana , Accardo Antonella
Published: February 2019

Magnetic resonance imaging (MRI) is one of the most important clinic diagnostic tool used to obtain high‐quality body images. The administration of low‐molecular‐weight Gd complex–based MRI contrast agents (CAs) permits to increase the 1H relaxation rate of nearby water molecules, thus modulating signal intensity and contrast enhancement. Even if highly accurate, MRI modality suffers from its low sensitivity. Moreover, low‐molecular‐weight CAs rapidly equilibrate between the intravascular and extravascular spaces after their administration. In order to improve their sensitivity and limit the extravasation phenomenon, several macromolecular and supramolecular multimeric gadolinium complexes (dendrimers, polymers, carbon nanostructures, micelles, and liposomes) have been designed until now. Because of their biocompatibility, low immunogenicity, low cost, and easy synthetic modification, peptides are attractive building blocks for the fabbrication of novel materials for biomedical applications. We report on the state of the art of supramolecular CAs obtained by self‐assembly of three different classes of building blocks containing a peptide sequence, a gadolinium complex, and, if necessary, a third functional portion achieving the organization process.
Ion Impact Induced Ultrafast Electron Dynamics in Finite Graphene‐Type Hubbard Clusters
Authors: Bonitz Michael , Balzer Karsten , Schlünzen Niclas , Rasmussen Maximilian Rodriguez , Joost Jan‐Philip
Published: February 2019

Strongly correlated systems of fermions have an interesting phase diagram arising from the Hubbard gap. Excitation across the gap leads to the formation of doubly occupied lattice sites (doublons) which offers interesting electronic and optical properties. Moreover, when the system is driven out of equilibrium interesting collective dynamics may arise that are related to the spatial propagation of doublons. Here, a novel mechanism that was recently proposed by the authors [Balzer et al., Phys. Rev. Lett. 121, 267602 (2018)] is verified by exact diagonalization and nonequilibrium Green functions (NEGF) simulations – fermionic doublon creation by the impact of energetic ions. The formation of a nonequilibrium steady state with homogeneous doublon distribution is reported. The effect should be particularly important for correlated finite systems, such as graphene nanoribbons, and directly observable with fermionic atoms in optical lattices. It is demonstrated that doublon formation and propagation in correlated lattice systems can be accurately simulated with NEGF. In addition to two‐time results, single‐time results within the generalized Kadanoff–Baym ansatz (GKBA) with Hartree–Fock propagators (HF‐GKBA) is presented. Finally systematic improvements of the GKBA that use correlated propagators (correlated GKBA) and a correlated initial state are discussed.
Human Fibrinogen for Maintenance and Differentiation of Induced Pluripotent Stem Cells in Two Dimensions and Three Dimensions
Authors: Gandhi Jarel K. , Knudsen Travis , Hill Matthew , Roy Bhaskar , Bachman Lori , Pfannkoch-Andrews Cynthia , Schmidt Karina N. , Metko Muriel M. , Ackerman Michael J. , Resch Zachary , Pulido Jose S. , Marmorstein Alan D.
Published: February 2019

Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three-dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture. iPSCs successfully adhered to and proliferated on fibrin hydrogels. The two-dimensional culture with fibrinogen allows for immediate adaption of culture models to a nonxenogeneic model. Similarly, multiple commercially available iPSC lines adhered to and proliferated on fibrinogen coated surfaces. iPSCs cultured on fibrinogen expressed similar levels of the pluripotent stem cell markers SSea4 (98.7% ± 1.8%), Oct3/4 (97.3% ± 3.8%), TRA1-60 (92.2% ± 5.3%), and NANOG (96.0% ± 3.9%) compared with iPSCs on Geltrex. Using a trilineage differentiation assay, we found no difference in the ability of iPSCs grown on fibrinogen or Geltrex to differentiate to endoderm, mesoderm, or ectoderm. Finally, we demonstrated the ability to differentiate iPSCs to endothelial cells using only fibrinogen coated plates. On the basis of these data, we conclude that human fibrinogen provides a readily available and inexpensive alternative to laminin-based products for the growth, expansion, and differentiation of iPSCs for use in research and clinical cell therapy applications. Stem Cells Translational Medicine  2019;8:512–521
Concise Review: Update on Retinal Pigment Epithelium Transplantation for Age-Related Macular Degeneration
Authors: Zarbin Marco , Sugino Ilene , Townes-Anderson Ellen
Published: February 2019

Retinal cell therapy can have the objectives of rescue (i.e., modulation of metabolic abnormalities primarily for sight preservation) as well as replacement (i.e., replace cells lost due to injury or disease for sight restoration as well as preservation). The first clinical trials of retinal pigment epithelium (RPE) transplantation for vision-threatening complications of age-related macular degeneration (AMD) have begun with some preliminary signs of success (e.g., improvement in vision in some patients, anatomic evidence of transplant-host integration with some evidence of host photoreceptor recovery, long-term survival of autologous induced pluripotent stem cell-derived RPE transplants without immune suppression) as well as limitations (e.g., limited RPE suspension survival in the AMD eye, limited tolerance for long-term systemic immune suppression in elderly patients, suggestion of uncontrolled cell proliferation in the vitreous cavity). RPE survival on aged and AMD Bruch’s membrane can be improved with chemical treatment, which may enhance the efficacy of RPE suspension transplants in AMD patients. Retinal detachment, currently used to deliver transplanted RPE cells to the subretinal space, induces disjunction of the first synapse in the visual pathway: the photoreceptor-bipolar synapse. This synaptic change occurs even in areas of attached retina near the locus of detachment. Synaptic disjunction and photoreceptor apoptosis associated with retinal detachment can be reduced with Rho kinase inhibitors. Addition of Rho kinase inhibitors may improve retinal function and photoreceptor survival after subretinal delivery of cells either in suspension or on scaffolds.
The association between stressful life events and respiratory infections during the first 4 years of life: The Environmental Determinants of Diabetes in the Young study
Authors: Roth Roswith , Lynch Kristian , Hyöty Heikki , Lönnrot Maria , Driscoll Kimberly A. , Bennett Johnson Suzanne ,   the TEDDY Study Group
Published: February 2019

The aim of this study was to conduct a prospective analysis of the association between negative life events (NLEs) and respiratory infections in children genetically at risk for islet autoimmunity (IA) and type 1 diabetes (T1D). Long‐ and short‐term temporal associations between NLEs and rate of respiratory infection episodes (RIEs) in 5,618 children in The Environmental Determinants of Diabetes in the Young study for at least 1 up to 4 years were analysed. All models were adjusted for demographic, day care, season of infection, and psychosocial factors associated with the rate of child RIEs between study visits. The rate of child RIEs was 26% higher in Europe (Sweden, Finland, Germany) than in the United States (rate ratio [RR] = 1.26, p < 0.001). However, the percentage of child NLEs (odds ratio [OR] = 1.18, p < 0.001) and mother NLEs (OR = 1.83, p < 0.001) was higher in the United States compared with Europe. In both continents (Europe, RR = 1.12, p < 0.001; United States, RR = 1.07, p = 0.006), high child cumulative NLEs (>1 NLE per year since study inception) was significantly associated with an increased rate of child RIEs. This large‐scale prospective study confirms observations that stress may increase the susceptibility for infections in paediatric populations and suggests at least one mechanism by which stress could increase risk for IA and T1D in genetically at risk children.
Systematic position of the enigmatic liverwort Mizutania (Mizutaniaceae, Marchantiophyta) inferred from molecular phylogenetic analyses
Authors: Masuzaki Hiroaki , Shimamura Masaki , Furuki Tatsuwo , Tsubota Hiromi , Yamaguchi Tomio , Majid Haji Mohamed Abdul , Deguchi Hironori
Published: February 2019

Phylogenetic analyses of liverworts using chloroplast rbcL and rps4 sequences were performed with special reference to the enigmatic thalloid liverwort, Mizutania riccardioides. The results showed that Mizutania is nested within leafy liverwort family Calypogeiaceae (subclass Jungermanniidae), thereby refuting the traditional interpretation that Mizutania is a member of the simple thalloid liverworts (subclass Metzgeriidae) related to Aneuraceae. Male plants with three ranked bracts, which are newly discovered in this study, also show a close morphological affinity to those of leafy liverworts. Parallel evolution of the flattened gametophyte seems to have occurred sporadically in the Jungermanniidae in association with adaptation to prostrate growth on the ground or on living leaves. The unistratose thalloid features of Mizutania are interpreted as an extremely reduced or highly specialized form of a creeping leafy liverwort. The rudimentary sexual branches which develop on the margins of the thallus are similar in many characteristics to those of Calypogeiaceae. We reduce the monotypic family Mizutaniaceae to a synonym of Calypogeiaceae.
A revised classification of Santalales
Authors: Nickrent Daniel L. , Malécot Valéry , Vidal-Russell Romina , Der Joshua P.
Published: February 2019

We present here a revised classification of Santalales, an angiosperm order that contains 18 families, 160 genera, and over 2200 species. Both nonparasitic and parasitic flowering plants occur in the traditionally circumscribed family Olacaceae whereas all other families are composed entirely of parasites. The five evolutionary radiations of aerial parasitism produced mistletoes that constitute most of the generic and specific diversity seen in the order. This classification, although based primarily upon results from molecular phylogenetic investigations, brings together all currently available information that contributes to our understanding of relationships among these plants. Monophyletic groups (clades) obtained from molecular analyses were named using a Linnaean ranked system. Four new families are named that formerly resided in Santalaceae s.l.: Amphorogynaceae, Cervantesiaceae, Comandraceae, and Nanodeaceae. A new tribal and subtribal classification for Loranthaceae is presented where nine new subtribe names are proposed.