bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology
Authors: Huff Wei X. , Kwon Jae Hyun , Henriquez Mario , Fetcko Kaleigh , Dey Mahua
Published: June 2019

Functional, tumor-specific CD8+ cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8+ effector T cell dysfunction. Among the many facets of CD8+ T cell dysfunction that have been recognized—tolerance, anergy, exhaustion, and senescence—CD8+ T cell senescence is incompletely understood. Naïve CD8+ T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8+CD28− senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8+CD28− senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8+ T cells could improve the efficacy of future anti-tumor immunotherapy.
Immortalization of Different Breast Epithelial Cell Types Results in Distinct Mitochondrial Mutagenesis
Authors: Kwon Sujin , Kim Susan , Nebeck Howard , Ahn Eun
Published: June 2019

Different phenotypes of normal cells might influence genetic profiles, epigenetic profiles, and tumorigenicities of their transformed derivatives. In this study, we investigate whether the whole mitochondrial genome of immortalized cells can be attributed to the different phenotypes (stem vs. non-stem) of their normal epithelial cell originators. To accurately determine mutations, we employed Duplex Sequencing, which exhibits the lowest error rates among currently-available DNA sequencing methods. Our results indicate that the vast majority of the observed mutations of the whole mitochondrial DNA occur at low-frequency (rare mutations). The most prevalent rare mutation types are C→T/G→A and A→G/T→C transitions. Frequencies and spectra of homoplasmic point mutations are virtually identical between stem cell-derived immortalized (SV1) cells and non-stem cell-derived immortalized (SV22) cells, verifying that both cell types were derived from the same woman. However, frequencies of rare point mutations are significantly lower in SV1 cells (5.79 × 10−5) than in SV22 cells (1.16 × 10−4). The significantly lower frequencies of rare mutations are aligned with a finding of longer average distances to adjacent mutations in SV1 cells than in SV22 cells. Additionally, the predicted pathogenicity for rare mutations in the mitochondrial tRNA genes tends to be lower (by 2.5-fold) in SV1 cells than in SV22 cells. While four known/confirmed pathogenic mt-tRNA mutations (m.5650 G>A, m.5521 G>A, m.5690 A>G, m.1630 A>G) were identified in SV22 cells, no such mutations were observed in SV1 cells. Our findings suggest that the immortalization of normal cells with stem cell features leads to decreased mitochondrial mutagenesis, particularly in RNA gene regions. The mutation spectra and mutations specific to stem cell-derived immortalized cells (vs. non-stem cell derived) have implications in characterizing the heterogeneity of tumors and understanding the role of mitochondrial mutations in the immortalization and transformation of human cells.
Isolation and Characterization of CsWRKY7, a Subgroup IId WRKY Transcription Factor from Camellia sinensis, Linked to Development in Arabidopsis
Authors: Chen Wei , Hao Wan-Jun , Xu Yan-Xia , Zheng Chao , Ni De-Jiang , Yao Ming-Zhe , Chen Liang
Published: June 2019

WRKY transcription factors (TFs) containing one or two WRKY domains are a class of plant TFs that respond to diverse abiotic stresses and are associated with developmental processes. However, little has been known about the function of WRKY gene in tea plant. In this study, a subgroup IId WRKY gene CsWRKY7 was isolated from Camellia sinensis, which displayed amino acid sequence homology with Arabidopsis AtWRKY7 and AtWRKY15. Subcellular localization prediction indicated that CsWRKY7 localized to nucleus. Cis-acting elements detected in the promotor region of CsWRKY7 are mainly involved in plant response to environmental stress and growth. Consistently, expression analysis showed that CsWRKY7 transcripts responded to NaCl, mannitol, PEG, and diverse hormones treatments. Additionally, CsWRKY7 exhibited a higher accumulation both in old leaves and roots compared to bud. Seed germination and root growth assay indicated that overexpressed CsWRKY7 in transgenic Arabidopsis was not sensitive to NaCl, mannitol, PEG, and low concentration of ABA treatments. CsWRKY7 overexpressing Arabidopsis showed a late-flowering phenotype under normal conditions compared to wild type. Furthermore, gene expression analysis showed that the transcription levels of the flowering time integrator gene FLOWERING LOCUS T (FT) and the floral meristem identity genes APETALA1 (AP1) and LEAFY (LFY) were lower in WRKY7-OE than in the WT. Taken together, these findings indicate that CsWRKY7 TF may participate in plant growth. This study provides a potential strategy to breed late-blooming tea cultivar.
High PD-L1 Expression Predicts for Worse Outcome of Leukemia Patients with Concomitant NPM1 and FLT3 Mutations
Authors: Brodská Barbora , Otevřelová Petra , Šálek Cyril , Fuchs Ota , Gašová Zdenka , Kuželová Kateřina
Published: June 2019

Compared to solid tumors, the role of PD-L1 in hematological malignancies is less explored, and the knowledge in this area is mostly limited to lymphomas. However, several studies indicated that PD-L1 is also overexpressed in myeloid malignancies. Successful treatment of the acute myeloid leukemia (AML) is likely associated with elimination of the residual disease by the immune system, and possible involvement of PD-L1 in this process remains to be elucidated. We analyzed PD-L1 expression on AML primary cells by flow cytometry and, in parallel, transcript levels were determined for the transcription variants v1 and v2. The ratio of v1/v2 cDNA correlated with the surface protein amount, and high v1/v2 levels were associated with worse overall survival (p = 0.0045). The prognostic impact of PD-L1 was limited to AML with mutated nucleophosmin and concomitant internal tandem duplications in the FLT3 gene (p less than 0.0001 for this particular AML subgroup).
Assessment of the Antiangiogenic and Anti-Inflammatory Properties of a Maslinic Acid Derivative and its Potentiation using Zinc Chloride
Authors: Pavel Ioana Zinuca , Csuk Rene , Danciu Corina , Avram Stefana , Baderca Flavia , Cioca Andreea , Moacă Elena-Alina , Mihali Ciprian-Valentin , Pinzaru Iulia , Muntean Danina Mirela , Dehelean Cristina Adriana
Published: June 2019

Maslinic acid is a pentacyclic triterpene with a plethora of biological activities, including anti-inflammatory, antioxidant, antimicrobial, cardioprotective, and antitumor effects. New derivatives with improved properties and broad-spectrum activity can be obtained following structural changes of the compound. The present study was aimed to characterize a benzylamide derivative of maslinic acid—benzyl (2α, 3β) 2,3-diacetoxy-olean−12-en-28-amide (EM2)—with respect to the anti-angiogenic and anti-inflammatory effects in two in vivo experimental models. Consequently, the compound showed good tolerability and lack of irritation in the chorioallantoic membrane assay with no impairment of the normal angiogenic process during the tested stages of development. In the acute ear inflammation murine model, application of EM2 induced a mild anti-inflammatory effect that was potentiated by the association with zinc chloride (ZnCl2). A decrease in dermal thickness of mice ears was observed when EM2 and ZnCl2 were applied separately or in combination. Moreover, hyalinization of the dermis appeared only when EM2 was associated with ZnCl2, strongly suggesting the role of their combination in wound healing.
Minimal Residual Disease Monitoring with Next-Generation Sequencing Methodologies in Hematological Malignancies
Authors: Sánchez Ricardo , Ayala Rosa , Martínez-López Joaquín
Published: June 2019

Ultra-deep next-generation sequencing has emerged in recent years as an important diagnostic tool for the detection and follow-up of tumor burden in most of the known hematopoietic malignancies. Meticulous and high-throughput methods for the lowest possible quantified disease are needed to address the deficiencies of more classical techniques. Precision-based approaches will allow us to correctly stratify each patient based on the minimal residual disease (MRD) after a treatment cycle. In this review, we consider the most prominent ways to approach next-generation sequencing methodologies to follow-up MRD in hematological neoplasms.
Latent Feature Group Learning for High-Dimensional Data Clustering
Authors: Wang Wenting , He Yulin , Ma Liheng , Huang Joshua Zhexue
Published: June 2019

In this paper, we propose a latent feature group learning (LFGL) algorithm to discover the feature grouping structures and subspace clusters for high-dimensional data. The feature grouping structures, which are learned in an analytical way, can enhance the accuracy and efficiency of high-dimensional data clustering. In LFGL algorithm, the Darwinian evolutionary process is used to explore the optimal feature grouping structures, which are coded as chromosomes in the genetic algorithm. The feature grouping weighting k-means algorithm is used as the fitness function to evaluate the chromosomes or feature grouping structures in each generation of evolution. To better handle the diverse densities of clusters in high-dimensional data, the original feature grouping weighting k-means is revised with the mass-based dissimilarity measure rather than the Euclidean distance measure and the feature weights are optimized as a nonnegative matrix factorization problem under the orthogonal constraint of feature weight matrix. The genetic operations of mutation and crossover are used to generate the new chromosomes for next generation. In comparison with the well-known clustering algorithms, LFGL algorithm produced encouraging experimental results on real world datasets, which demonstrated the better performance of LFGL when clustering high-dimensional data.
Predictive Factors of 2-Year Postoperative Outcomes in Patients with Spontaneous Cerebellar Hemorrhage
Authors: Lee Tsung-Han , Huang Yu-Hua , Su Tsung-Ming , Chen Chih-Feng , Lu Cheng-Hsien , Lee Hsiang-Lin , Tsai Hui-Ping , Sung Wen-Wei , Kwan Aij-Lie
Published: June 2019

Spontaneous cerebellar hemorrhage (SCH) is associated with high patient mortality and morbidity, but the clinical and radiographic predictors of the postoperative outcome have not been widely addressed in the literature. The purpose of this study was to define the prognostic factors for the two-year postoperative outcome in patients with SCH. We conducted a retrospective study of 48 consecutive patients with SCH who underwent neurosurgical intervention. Correlation analysis was performed to examine the possible link between clinical and radiographic parameters, and the National Institutes of Health Stroke Scale (NIHSS) score at each patient’s discharge and the two-year postoperative outcome as defined according to the Glasgow outcome scale (GOS). A total of 48 patients with SCH underwent neurological surgery, which included suboccipital craniectomy and/or external ventricular drainage (EVD). The mean patient age was 63 years. Nine patients underwent suboccipital craniectomy only; 38 underwent both suboccipital craniectomy and EVD. The overall mortality rate was 35.4%. Fourteen patients (29.2%) had good outcomes. A good outcome on the GOS at 2 years after surgical treatment of SCH was associated with the NIHSS score at discharge. An increase of one point in a patient’s NIHSS score at discharge following neurological surgery will increase the probability of a poor two-year postoperative outcome by 28.5%.
Effect of Statin on Cancer Incidence: An Umbrella Systematic Review and Meta-Analysis
Authors: Jeong Gwang Hun , Lee Keum Hwa , Kim Jong Yeob , Eisenhut Michael , Kronbichler Andreas , van der Vliet Hans J. , Hong Sung Hwi , Shin Jae Il , Gamerith Gabriele
Published: June 2019

Statins are reported to reduce the risk of cancer, but the results of various published studies have been contradictory. We carried out an umbrella review to provide an overview and understand the strength of evidence, extent of potential biases, and validity of claimed associations between the use of statins and cancer incidence. We comprehensively re-analyzed the data of meta-analyses of randomized controlled trials (RCTs) and observational studies on associations between statin use and cancer incidence. We also assessed the strength of evidence of the re-analyzed outcomes, which were determined from the criteria including statistical significance of the p-value of random-effects, as well as fixed-effects meta-analyses, small study effects, between-study heterogeneity, and a 95% prediction interval. Using a conventional method to assess the significance of meta-analysis (p-value < 0.05), statins had a statistically significant effect on reducing cancer incidence in 10 of 18 types of cancer. When we graded the level of evidence, no cancer type showed convincing evidence, and four cancers (esophageal cancer, hematological cancer, leukemia, and liver cancer) showed suggestive evidence of a preventive effect. There was weak evidence of an association with six cancers, and no significance for the remaining eight cancers. None of the meta-analyses of RCTs on the association of statin and cancer incidence showed a statistical significance. Although there was a preventive effect of statin on cancer incidence in 10 of the 18 cancer types, the evidence supporting the use of statins to reduce cancer incidence was low. Therefore, the associations between statin use and cancer incidence should be carefully considered by clinicians.
Initial Experience in CT-Guided Percutaneous Transthoracic Needle Biopsy of Lung Lesions Performed by a Pulmonologist
Authors: Ahn June Hong , Jang Jong Geol
Published: June 2019

In the diagnosis of lung lesions, computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) has a high diagnostic yield and a low complication rate. The procedure is usually performed by interventional radiologists, but the diagnostic yield and safety of CT-guided PTNB when performed by pulmonologists have not been evaluated. A retrospective study of 239 patients who underwent CT-guided PTNB at Yeungnam University Hospital between March 2017 and April 2018 was conducted. A pulmonologist performed the procedure using a co-axial technique with a 20-gauge needle. Then diagnostic yield and safety were assessed. The overall sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of malignancy were 96.1% (171/178), 100% (46/46), 100% (171/171), and 86.8% (46/53), respectively. The diagnostic accuracy was 96.9% (217/224) and the overall complication rate was 33.1% (82/248). Pneumothorax, hemoptysis, and hemothorax occurred in 27.0% (67/248), 5.2% (13/248), and 0.8% (2/248) of the patients, respectively. Univariate analyses revealed that pneumothorax requiring chest tube insertion was a significant risk factor (odds ratio, 25.0; p < 0.001) for diagnostic failure. CT-guided PTNB is a safe procedure with a high diagnostic accuracy, even when performed by an inexperienced pulmonologist. The results were similar to those achieved by interventional radiologists as reported in previously published studies.
Fabrication and Application of Carboxymethyl Cellulose-Carbon Nanotube Aerogels
Authors: Long Linyu , Li Fenfen , Shu Mengying , Zhang Caili , Weng Yunxuan
Published: June 2019

In this study, composite aerogels with excellent mechanical properties were prepared by using carboxymethyl cellulose (CMC) as raw materials, with carboxylic carbon nanotubes (CNTs) as reinforcement. By controlling the mass fraction of CNTs, composite aerogels with different CNTs were prepared, and the surface morphology, specific surface area, compressive modulus, density and adsorption capacities towards different oils were studied. Compared to the pure CMC aerogel, the specific surface areas of CMC/CNTs were decreased because of the agglomeration of CNTs. However, the densities of composite aerogels were lower than pure CMC aerogel. This is because the CNTs were first dispersed in water and then added to CMC solution. The results indicated that it was easy for the low CMC initial concentration to be converted to low density aerogel. The compressive modulus was increased from 0.3 MPa of pure CMC aerogel to 0.5 MPa of 5 wt % CMC/CNTs aerogel. Meanwhile, the prepared aerogels showed promising properties as the adsorption materials. Because of the high viscosity, liquid possesses strong adhesion to the pore wall, the adsorption capacity of the CMC aerogel to the liquid increases as the viscosity of the liquid increases.
Synthesis, Characterization, and Crystal Structures of Imides Condensed with p-Phenylamino(Phenyl) Amine and Fluorescence Property
Authors: Zhang Jing , Ma Huaibo
Published: June 2019

A series of aromatic diimide and monoimide compounds condensed with p-phenylamino(phenyl)amine were synthesized and confirmed by Proton Nuclear Magnetic Resonance (1H NMR), Carbon-13 Nuclear Magnetic Resonance (13C NMR), Fourier Transform Infrared Spectroscopy (FT-IR), Elemental Analysis (EA), and High Resolution Mass Spectroscopy (HRMS). Meanwhile, single crystal X-ray diffraction showed the existence of intermolecular N···O hydrogen bonds, which affected the thermal stabilities of corresponding compounds by the support of Thermalgravimetric Analysis (TGA) curves. The steady-state UV-vis absorption peaks of synthetic compounds 1–6 appeared in the range of 220–380 nm. Fluorescence emission spectra showed peaks in the range of 290–420 nm. Meanwhile, deep-blue or violet-blue emissions for 2, 4, and 5 in THF under excitations of 254 nm and 365 nm, respectively, were observed at room temperature in air. Furthermore, Differential pulse voltammetry (DPV) and cyclic voltammogram CV were conducted within −1.5–+1.5 V to show quasi-reversible behavior for conjugated compounds and irreversible behavior for less conjugated ones.
Application of Fixed-Point Theory for a Nonlinear Fractional Three-Point Boundary-Value Problem
Authors: Pourhadi Ehsan , Saadati Reza , Ntouyas Sotiris K.
Published: June 2019

Throughout this paper, via the Schauder fixed-point theorem, a generalization of Krasnoselskii’s fixed-point theorem in a cone, as well as some inequalities relevant to Green’s function, we study the existence of positive solutions of a nonlinear, fractional three-point boundary-value problem with a term of the first order derivative ( a C D α x ) ( t ) = f ( t , x ( t ) , x ′ ( t ) ) , a < t < b , 1 < α < 2 , x ( a ) = 0 , x ( b ) = μ x ( η ) , a < η < b , μ > λ , where λ = b − a η − a and a C D α denotes the Caputo’s fractional derivative, and f : [ a , b ] × R × R → R is a continuous function satisfying the certain conditions.
A Meta-Model-Based Multi-Objective Evolutionary Approach to Robust Job Shop Scheduling
Authors: Wu Zigao , Yu Shaohua , Li Tiancheng
Published: June 2019

In the real-world manufacturing system, various uncertain events can occur and disrupt the normal production activities. This paper addresses the multi-objective job shop scheduling problem with random machine breakdowns. As the key of our approach, the robustness of a schedule is considered jointly with the makespan and is defined as expected makespan delay, for which a meta-model is designed by using a data-driven response surface method. Correspondingly, a multi-objective evolutionary algorithm (MOEA) is proposed based on the meta-model to solve the multi-objective optimization problem. Extensive experiments based on the job shop benchmark problems are conducted. The results demonstrate that the Pareto solution sets of the MOEA are much better in both convergence and diversity than those of the algorithms based on the existing slack-based surrogate measures. The MOEA is also compared with the algorithm based on Monte Carlo approximation, showing that their Pareto solution sets are close to each other while the MOEA is much more computationally efficient.
Female Volleyball Players Are More Prone to Cortisol Anticipatory Stress Response than Sedentary Women
Authors: Dziembowska Inga , Wójcik Małgorzata , Hołyńska-Iwan Iga , Litwic-Kaminska Kamila , Słomka Artur , Żekanowska Ewa
Published: June 2019

Background and Objectives: Top-level sports performance places heavy physical and psychological demands on elite-level athletes, which can be a source of increased levels of stress. Therefore, high-level volleyball players may present altered cardiovascular and endocrinological stress response during stressful events. Although many previous studies have examined the response to stress on athletes, most of them regarded only males, while the impact of the female menstrual cycle has rarely been taken into account. We aimed to study psychophysiological response to anticipatory stressor through analysis of heart rate, self-reported anxiety level, and salivary cortisol in healthy young female athletes by minimalizing the effect of confounders. Materials and Methods: A total of 55 females (25 members of the best league for female volleyball players in Poland and 30 sedentary-lifestyle control subjects) in the follicular phase of their menstrual cycle were exposed to mental arithmetic tasks as an experimental imitation of the stressor. Volleyball players were significantly taller than sedentary individuals (177.1 ± 3.4 cm vs. 173.3 ± 3.4 cm, respectively, p = 0.034), but did not differ in weight (73.6 ± 5.2 kg vs. 70 ± 4.23 kg, respectively, p = 0.081), body mass index (BMI) (23.5 ± 1.13 vs. 24.1 ± 1.45, respectively, p = 0.060), and age (22 ± 1.11 vs. 23 ± 1.14 years, respectively, p = 0.2). Their stress responses were assessed through self-reported anxiety levels and physiological measurements of salivary cortisol concentrations and heart rate (HR). Results: For HR, significant effects of time (F(2,120) = 21.34, p < 0.001, η2 = 0.26) were found, but not for training status (F(1,60) = 2.69, p = 0.106, η2 = 0.04). For cortisol levels, the analysis showed the main effects of time (F(3,180) = 11.73, p < 0.001, η2 = 0.16) and training status (F(1,60) = 4.69, p = 0.034, η2 = 0.07) and a significant interaction between training status and time (F(3,180) = 3.07, p = 0.029, η2 = 0.05). Post-hoc analyses showed higher cortisol concentrations among volleyball players following the math task (all p < 0.001), as well as higher cortisol concentrations in S2, S3, and S4 compared to S1 in volleyball players (all p < 0.001). We observed also a significant increase in state anxiety in both groups (all p < 0.001), but no differences in state anxiety levels between groups. Conclusion: Female volleyball players may not differ in subjective graduation of stressors; however, exposure to training-based stressors seems to promote cortisol response to the anticipated stressor.
Influence of AlN Nanoparticle Addition on Microstructure and Mechanical Properties of Extruded Pure Magnesium and an Aluminum-Free Mg-Zn-Y Alloy
Authors: Giannopoulou Danai , Dieringa Hajo , Bohlen Jan
Published: June 2019

A pure Mg and a ZW0303 alloy metal matrix nanocomposite reinforced with AlN nanoparticles were prepared assisted by mechanical stirring and sonication for deagglomeration of particles. The produced nanocomposites were investigated to determine the influence of the AlN nanoparticles during indirect extrusion on the microstructure and texture development, as well as the resulting hardness and mechanical properties. For pure Mg, grain refinement and hardness increase due to the addition of AlN were revealed in the as-cast and the extruded condition. For ZW0303, the same was found for the as-cast condition. However, contamination of the alloy with Al significantly changes the recrystallization behavior during extrusion. This is directly related to the removal of solute Y due to the formation of intermetallic particles. Particle and grain size effects were distinguished for this alloy.
Hybrid Nanosecond Laser Processing and Heat Treatment for Rapid Preparation of Super-Hydrophobic Copper Surface
Authors: Ma Linxu , Wang Lina , Li Chengying , Guo Jian , Shrotriya Pranav , Deng Cui , Zhao Jingnan
Published: June 2019

The super-hydrophobic copper surface was obtained by using a nanosecond pulsed laser. Different micro- and nano-structures were fabricated by changing the laser scanning interval and scanning speed, before heating in an electric heater at 150 °C for two hours to explore the effect of laser parameters and heat treatment on the wettability of the copper surface. It was found that the laser-treated copper surface is super-hydrophilic, and then, after the heat treatment, the surface switches to hydrophobic or even super-hydrophobic. The best super-hydrophobic surface’s apparent contact angle (APCA) was 155.6°, and the water sliding angle (WSA) was 4°. Super-hydrophobic copper is corrosion-resistant, self-cleaning, and dust-proof, and can be widely used in various mechanical devices.
Numerical Simulation of Macrosegregation with Solid Deformation During the Solidification of Steel Ingots Using a Single-Phase/Two-Phase Integrated Model
Authors: Chen Kangxin , Shen Houfa
Published: June 2019

Macrosegregation, a serious defect formed during the solidification of steel ingots, impairs the performance of the final components. To predict macrosegregation caused by thermal-solutal convection and solid deformation, a volume-averaged single-phase/two-phase integrated model is developed. During the deformation stage, the two-phase model coupling the solid deformation and liquid flow in the mushy zone is utilized. Before or after the deformation stage, the motion of the solid phase is neglected, and the single-phase model is solved. A 450 kg steel ingot punching test is considered for application. The results show that when the solid shell of the ingot is being punched, the solid phase in the mushy core at punching height is compressed, and a relative liquid flow is induced. This in turn causes a transition of positive segregation to negative segregation in the compressed mushy core of the ingot. According to numerical sensitivity tests of different punching parameters, as the punching start time and punching velocity increase, the effect of punching on macrosegregation will be smaller. It is demonstrated that the single-phase/two-phase integrated model can predict macrosegregation in the steel ingots which are deformed during solidification.
A Proposal for the Application of Failure Assessment Diagrams to Subcritical Hydrogen Induced Cracking Propagation Processes
Authors: Arroyo Martínez Borja , Álvarez Laso José Alberto , Gutiérrez-Solana Federico , Cayón Martínez Alberto , Jirón Martínez Yahoska Julieth , Seco Aparicio Ana Ruht
Published: June 2019

In this work, an optimization proposal for a model based on the definition of regions for crack propagation by means of the micromechanical comparison by SEM images and its application to failure assessment diagrams (FADs) is presented. It consists in three approaches. (1) The definition of the crack propagation initiation in the elastic-plastic range. (2) A slight modification of the zones in which the FAD is divided for hydrogen induced cracking (HIC) conditions. (3) The introduction of a simple correction for the definition of the Kr coordinate of the FAD to take into account the fracture toughness reduction caused by an aggressive environment, instead of using a fracture parameter obtained from a test in air. For the experimental work, four medium and high strength steels exposed to a cathodic charge and cathodic protection environments were employed, studying two different loading rates in each case, and testing C(T) samples under slow rates in the environment. The study was completed with a subsequent fractographic analysis by SEM. A good degree of fulfilment was appreciated in both materials and environmental conditions, showing the validity of the predictions supplied by the FAD optimization model proposal, which constitutes an advance in the accuracy of the FAD predictive model.
Dislocation Density-Based Modeling of Dynamic Recrystallized Microstructure and Process in Friction Stir Spot Welding of AA6082
Authors: Gao Zeng , Feng Jianguang , Wang Zhenjiang , Niu Jitai , Sommitsch Christof
Published: June 2019

This work mainly focuses on a series of microstructural analysis and predictions regarding dynamic recrystallization behavior, change in grain size, and dislocation density. Additionally, this study includes the shape prediction of the stir zone formed during friction stir spot welding. Microstructure analysis of the joint reveals that the mechanism of dynamic recrystallization in the stir zone is geometric dynamic recrystallization. A set of constitutive equations based on dislocation density is established and implemented in DEFORM-3D software to predict dynamic recrystallization during friction stir spot welding of AA6082. From the experimental and model predictions, it is observed that the original microstructure in the stir zone is completely replaced by a recrystallized fine grained microstructure. There is satisfactory agreement between the experimental grain size and the simulated results. In addition, the predicted shape of the stir zone fits quite well with the experimental shape as well.
Dynamic Changes of Plasma Metabolome in Response to Severe Feed Restriction in Pregnant Ewes
Authors: Guo Changzheng , Xue Yanfeng , Seddik Hossam-eldin , Yin Yuyang , Hu Fan , Mao Shengyong
Published: June 2019

Maternal metabolic disorders in ewes induced by energy deficiency have a detrimental effect on the maternal health and lambs. However, the dynamic processes of metabolic disorders are unknown. Therefore, this study attempted to explore the dynamic changes of maternal metabolism based on metabolomics approach during energy deficiency in pregnant ewes. Twenty pregnant Hu sheep were fed a basic diet or a 70% restricted basic diet. The HPLC-MS platform was applied to identify blood metabolites. Principal component analysis of blood samples based on their metabolic profile showed that blood samples of feed restriction group differed after the treatment. In particular, when comparing both groups, there were 120, 129, and 114 differential metabolites at day 5, day 10, and day 114 between the two groups, respectively. Enrichment analysis results showed that four metabolic pathways (glycerophospholipid metabolism, linoleic acid metabolism, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis) at day 5, four metabolic pathways (aminoacyl-tRNA biosynthesis, aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, and citrate cycle) at day 10, and nine metabolic pathways (aminoacyl-tRNA biosynthesis, synthesis and degradation of ketone bodies, glycerophospholipid metabolism, butanoate metabolism, linoleic acid metabolism, citrate cycle, alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, and arginine and proline metabolism) at day 15 were significantly enriched between the two groups. These findings revealed temporal changes of metabolic disorders in pregnant ewes caused by severe feed restriction, which may provide insights into mitigation measures.
Epithermal Bicolor Black and White Calcite Spheres from Herja Ore Deposit, Baia Mare Neogene Ore District, Romania-Genetic Considerations
Authors: Mârza Ioan , Tămaș Călin Gabriel , Tetean Romulus , Andreica Alina , Denuț Ioan , Kovács Réka
Published: June 2019

White, black, or white and black calcite spheres were discovered during the 20th century within geodes from several Pb-Zn ± Au-Ag epithermal vein deposits from the Baia Mare ore district, Eastern Carpathians, Romania, with the Herja ore deposit being the maiden occurrence. The black or black and white calcite spheres are systematically accompanied by needle-like sulfosalts which are known by the local miners as “plumosite”. The genesis of epithermal spheres composed partly or entirely of black calcite is considered to be related to the deposition of calcite within voids filled by hydrothermal fluids that contain acicular crystals of sulfosalts, mostly jamesonite in suspension. The proposed genetic model involves gravitational concentration of sulfosalt acicular crystals towards the base of open spaces within paleochannels of epithermal fluid flow and the subsequent formation of calcite spheres by geochemical self organization of amorphous calcium carbonate that crystallized to calcite via vaterite.
Botanical Sources, Chemistry, Analysis, and Biological Activity of Furanocoumarins of Pharmaceutical Interest
Authors: Bruni Renato , Barreca Davide , Protti Michele , Brighenti Virginia , Righetti Laura , Anceschi Lisa , Mercolini Laura , Benvenuti Stefania , Gattuso Giuseppe , Pellati Federica
Published: June 2019

The aim of this work is to provide a critical review of plant furanocoumarins from different points of view, including their chemistry and biosynthetic pathways to their extraction, analysis, and synthesis, to the main biological activities found for these active compounds, in order to highlight their potential within pharmaceutical science. The limits and the possible improvements needed for research involving these molecules are also highlighted and discussed.
Kynurenic Acid and Its Analogs Are Beneficial Physiologic Attenuators in Bdelloid Rotifers
Authors: Datki Zsolt , Galik-Olah Zita , Bohar Zsuzsanna , Zadori Denes , Fulop Ferenc , Szatmari Istvan , Galik Bence , Kalman Janos , Vecsei Laszlo
Published: June 2019

The in vivo investigation of kynurenic acid (KYNA) and its analogs is one of the recent exciting topics in pharmacology. In the current study we assessed the biological effects of these molecules on bdelloid rotifers (Philodina acuticornis and Adineta vaga) by monitoring changes in their survival and phenotypical characteristics. In addition to longitudinal (slowly changing) markers (survival, number of rotifers alive and body size index), some dynamic (quickly responding) ones (cellular reduction capacity and mastax contraction frequency) were measured as well. KYNA and its analogs increased longevity, reproduction and growth, whereas reduction capacity and energy-dependent muscular activity decreased conversely. We found that spermidine, a calorie restriction mimetic, exerted similar changes in the applied micro-invertebrates. This characterized systemic profile evoked by the above-mentioned compounds was named beneficial physiologic attenuation. In reference experiments, using a stimulator (cyclic adenosine monophosphate) and a toxin (sodium azide), all parameters changed in the same direction (positively or negatively, respectively), as expected. The currently described adaptive phenomenon in bdelloid rotifers may provide holistic perspectives in translational research.
Metal-Free Air Oxidation in a Convenient Cascade Approach for the Access to Isoquinoline-1,3,4(2H)-triones
Authors: Di Mola Antonia , Tedesco Consiglia , Massa Antonio
Published: June 2019

Herein we describe a very useful application of the readily available trifunctional aromatic ketone methyl-2-(2-bromoacetyl)benzoate in reactions with primary amines. An unexpected in situ air oxidation that follows a cascade process allowed the access to a series of isoquinoline-1,3,4(2H)-triones, a class of heterocyclic compounds of great interest containing an oxygen-rich heterocyclic scaffold. A modification of the original protocol, utilizing a Staudinger reaction in the presence of trimethylphosphine, was necessary for the synthesis of Caspase inhibitor trione with free NH group.
Optical Sensing of Humidity Using Polymer Top-Covered Bragg Stacks and Polymer/Metal Thin Film Structures
Authors: Lazarova Katerina , Christova Darinka , Georgiev Rosen , Georgieva Biliana , Babeva Tsvetanka
Published: June 2019

Thin films with nanometer thicknesses in the range 100–400 nm are prepared from double hydrophilic copolymers of complex branched structures containing poly(N,N-dimethyl acrylamide) and poly(ethylene oxide) blocks and are used as humidity sensitive media. Instead of using glass or opaque wafer for substrates, polymer thin films are deposited on Bragg stacks and thin (30 nm) sputtered Au–Pd films thus bringing color for the colorless polymer/glass system and enabling transmittance measurements for humidity sensing. All samples are characterized by transmittance measurements at different humidity levels in the range from 5% to 90% relative humidity. Additionally, the humidity induced color change is studied by calculating the color coordinates at different relative humidity using measured spectra of transmittance or reflectance. A special attention is paid to the selection of wavelength(s) of measurements and discriminating between different humidity levels when sensing is performed by measuring transmittance at fixed wavelengths. The influence of initial film thickness, sensor architecture, and measuring configuration on sensitivity is studied. The potential and advantages of using top covered Bragg stacks and polymer/metal thin film structures as humidity sensors with simple optical read-outs are demonstrated and discussed.
Arginine/Nanocellulose Membranes for Carbon Capture Applications
Authors: Venturi Davide , Chrysanthou Alexander , Dhuiège Benjamin , Missoum Karim , Giacinti Baschetti Marco
Published: June 2019

The present study investigates the influence of the addition of l-arginine to a matrix of carboxymethylated nanofibrillated cellulose (CMC-NFC), with the aim of fabricating a mobile carrier facilitated transport membrane for the separation of CO2. Self-standing films were prepared by casting an aqueous suspension containing different amounts of amino acid (15–30–45 wt.%) and CMC-NFC. The permeation properties were assessed in humid conditions (70–98% relative humidity (RH)) at 35 °C for CO2 and N2 separately and compared with that of the non-loaded nanocellulose films. Both permeability and ideal selectivity appeared to be improved by the addition of l-arginine, especially when high amino-acid loadings were considered. A seven-fold increment in carbon dioxide permeability was observed between pure CMC-NFC and the 45 wt.% blend (from 29 to 220 Barrer at 94% RH), also paired to a significant increase of ideal selectivity (from 56 to 185). Interestingly, while improving the separation performance, water sorption was not substantially affected by the addition of amino acid, thus confirming that the increased permeability was not related simply to membrane swelling. Overall, the addition of aminated mobile carriers appeared to provide enhanced performances, advancing the state of the art for nanocellulose-based gas separation membranes.
Replication of Crohn’s Disease Mucosal E. coli Isolates inside Macrophages Correlates with Resistance to Superoxide and Is Dependent on Macrophage NF-kappa B Activation
Authors: Tawfik Ahmed , Knight Paul , Duckworth Carrie A. , Pritchard D. Mark , Rhodes Jonathan M. , Campbell Barry J.
Published: June 2019

Mucosa-associated Escherichia coli are increased in Crohn’s disease (CD) and colorectal cancer (CRC). CD isolates replicate within macrophages but the specificity of this effect for CD and its mechanism are unclear. Gentamicin exclusion assay was used to assess E. coli replication within J774.A1 murine macrophages. E. coli growth was assessed following acid, low-nutrient, nitrosative, oxidative and superoxide stress, mimicking the phagolysosome. Twelve of 16 CD E. coli isolates replicated >2-fold within J774.A1 macrophages; likewise for isolates from 6/7 urinary tract infection (UTI), 8/9 from healthy subjects, compared with 2/6 ulcerative colitis, 2/7 colorectal cancer and 0/3 laboratory strains. CD mucosal E. coli were tolerant of acidic, low-nutrient, nitrosative and oxidative stress. Replication within macrophages correlated strongly with tolerance to superoxide stress (rho = 0.44, p = 0.0009). Exemplar CD E. coli HM605 and LF82 were unable to survive within Nfκb1-/- murine bone marrow-derived macrophages. In keeping with this, pre-incubation of macrophages with hydrocortisone (0.6 µM for 24 h) caused 70.49 ± 12.11% inhibition of intra-macrophage replication. Thus, CD mucosal E. coli commonly replicate inside macrophages, but so do some UTI and healthy subject strains. Replication correlates with resistance to superoxide and is highly dependent on macrophage NF-κB signalling. This may therefore be a good therapeutic target.
Severe Clinical Outcomes of Tuberculosis in Kharkiv Region, Ukraine, Are Associated with Beijing Strains of Mycobacterium tuberculosis
Authors: Konstantynovska Olha , Rekrotchuk Mariia , Hrek Ivan , Rohozhyn Anton , Rudova Nataliia , Poteiko Petro , Gerilovych Anton , Bortz Eric , Solodiankin Oleksii
Published: June 2019

Genotypic variation in Beijing lineages of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), has been associated with hyper virulence and the spread of extensively and multiple drug (X/MDR) resistant MTB strains in Eastern Europe, Central Asia, and East Asia. The clinical outcomes of 215 new cases of TB among the population of the Kharkiv region of Eastern Ukraine were analyzed to uncover factors associated with severe infection. Infecting MTB strains were profiled by 5 locus exact tandem repeats (ETRs) and 15 locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) genotyping. Among diverse MTB genotypes discovered in Ukraine, the Beijing genotype (MIRU-VNTR 42425) was significantly associated with risk factors for severe outcomes of disease in the study population, including TB/HIV co-infection and treatment failure. Strain replacement (superinfection) was observed in 10 patients, suggesting repeated exposure to novel MTB strains in hospital or community settings. Inclusion of MTB genotyping data may identify at-risk patients and improve treatment adherence to prevent X/MDR development for effective public health response against tuberculosis in Ukraine.
Mechanically Robust Gastroretentive Drug-Delivery Systems Capable of Controlling Dissolution Behaviors of Coground β-Lapachone
Authors: Kim Hyeongmin , Lee Chung-Lyol , Lee Seohyun , Lee Tae Jin , Haleem Iqra , Lee Younghong , Hwang Na Jung , Shim Kyusun , Kim Dohyun , Lee Jaehwi
Published: June 2019

In this study, we aimed to design a highly swellable and mechanically robust matrix tablet (SMT) as a gastroretentive drug-delivery system (GRDDS) capable of improving the dissolution behavior of β-lapachone with low aqueous solubility. For the preparation of SMTs, the cogrinding technique and freeze–thaw method were used to disperse β-lapachone in SMTs in an amorphous state and to enhance the swelling and mechanical properties of SMTs, respectively. As a result, the crystallinity of coground β-lapachone incorporated in the SMTs was found to be considerably decreased; thereby, the dissolution rates of the drug in a simulated gastric fluid could be substantially increased. The SMTs of β-lapachone also demonstrated significantly enhanced swelling and mechanical properties compared to those of a marketed product. The reason for this might be because the physically crosslinked polymeric networks with a porous structure that were formed in SMTs through the freeze–thaw method. In addition, β-lapachone was gradually released from the SMTs in 6 h. Therefore, SMTs of β-lapachone developed in this study could be used as GRDDS with appropriate swelling and mechanical properties for improving the dissolution behavior of hydrophobic drugs such as β-lapachone.
An In Vitro Evaluation, on Polyurethane Foam Sheets, of the Insertion Torque (IT) Values, Pull-Out Torque Values, and Resonance Frequency Analysis (RFA) of NanoShort Dental Implants
Authors: Comuzzi Luca , Iezzi Giovanna , Piattelli Adriano , Tumedei Margherita
Published: June 2019

Objectives: The aim of this study was to investigate, in polyurethane foam sheets, the primary implant stability of a NanoShort implant compared to a self-condenser implant and to a standard, conventional implant. Materials and Methods: Three implant designs were evaluated in the present in vitro investigation: The Test implant (NanoShort), the Control A implant (self-condenser), and the Control B implant (standard design). The study was conducted by comparing the insertion torque values, the pull-out strength values, and the resonance frequency analysis (RFA) values of the Test and Control A and B implants inserted in polyurethane foam models of different thicknesses and densities. The foam densities were 10, 20, and 30 pounds per cubic foot (pcf). Three thicknesses of polyurethane foams (1, 2, 3 mm) were evaluated for a total of 640 experimental sites. Results: The Pearson correlation showed a moderate/strong correlation between all study groups (r > 0.3) for insertion torque and pull-out strength levels. Increased stability of the Test implants was obtained in 3 mm polyurethane sheets. The 2.5 and 3.5 mm Test implants presented good stability in 3 mm polyurethane sheets of 20–30 pcf densities. The Control implants showed better results compared to the Test implants in 1, 2, and 3 mm polyurethane sheets with densities of 10, 20, and 30 pcf. Conclusions: The NanoShort dental implant evaluated in this in vitro study showed a high level of stability in some experimental conditions, and could represent a useful tool, especially in the posterior mandible, as an alternative to vertical augmentation procedures.
A Universal Photochemical Method to Prepare Carbohydrate Sensors Based on Perfluorophenylazide Modified Polydopamine for Study of Carbohydrate-Lectin Interactions by QCM Biosensor
Authors: Guo Lili , Chao Shuang , Huang Pei , Lv Xiukai , Song Quanquan , Wu Chunli , Pei Yuxin , Pei Zhichao
Published: June 2019

A universal photochemical method to prepare carbohydrate sensors based on perfluorophenylazide (PFPA) modified polydopamine (PDA) for the study of carbohydrate–lectin interactions by a quartz crystal microbalance (QCM) biosensor was developed. The PFPA was immobilized on PDA-coated gold sensors via Schiff base reactions. Upon light irradiation, the underivatized carbohydrates were inserted into the sensor surface, including mannose, galactose, fucose and N-acetylglucosamine (GlcNAc). Carbohydrate sensors were evaluated for the binding to a series of plant lectins. A kinetic study of the interactions between mannose and concanavalin A (Con A), fucose and Ulex europaeus agglutinin I (UEA-I) were performed. This method can eliminate the tedious modification of carbohydrates, improve the experimental efficiency, and reduce the experimental cost, which is of great significance for the development of QCM biosensors and the study of biomolecular interactions.
Numerical Study of Pressure Fluctuation and Unsteady Flow in a Centrifugal Pump
Authors: Bai Ling , Zhou Ling , Han Chen , Zhu Yong , Shi Weidong
Published: June 2019

A pump is one of the most important machines in the processes and flow systems. The operation of multistage centrifugal pumps could generate pressure fluctuations and instabilities that may be detrimental to the performance and integrity of the pump. In this paper, a numerical study of the influence of pressure fluctuations and unsteady flow patterns was undertaken in the pump flow channel of three configurations with different diffuser vane numbers. It was found that the amplitude of pressure fluctuation in the diffuser was increased gradually with the increase in number of diffuser vanes. The lower number of diffuser vanes was beneficial to obtain a weaker pressure fluctuation intensity. With the static pressure gradually increasing, the effects of impeller blade passing frequency attenuated gradually, and the effect of diffuser vanes was increased gradually.