bluuebunny/crossref_metadata_2025 huggingface dataset:
基于复杂性理论的信息系统项目整体管理研究
Authors: 张 远惠
Published: September 2019

20世纪70年代以来,复杂性理论开始成为业界学者们进行跨学科研究的重点,有关复杂性理论研究的成果被广泛地应用于各学科——地质学、生态学、经济学、心理学和管理学等,并不断得到发展和创新。本文将复杂性理论应用于信息系统项目管理方面,倡导信息系统项目管理者应采用系统整体性思维方式,通过遵循复杂系统具有的主要特征,如与环境的共演化性、非线性、突现性和自组织性等,创造性地解决管理过程中出现的各种问题,如复杂性理论中的“混沌边缘”理论概念,其在管理中的应用表现为：最成功的管理并不是靠完全的控制,而是使系统运行于“混沌边缘”,而这里是最容易突现出创造性解决方案的空间,可为系统带来新的有序状态。这一观点也是时下业界研究的热点。
工程教育专业认证要求下的现代控制理论课程教学改革
Authors: 高 瑜 , 陈 良
Published: September 2019

工程教育是我国高等教育的重要组成部分,也是国家工业化进程中的重要环节,专业认证的实施有助于提升高校工程教育的质量,同时实现教育体系与国际化标准的接轨。作为工科自动化专业的一门专业必修课程,现代控制理论已逐渐取代经典控制理论占据主导地位。本文主要分析该课程的特点和教学目标,探讨在工程教育专业认证的背景下,具体的教学改革措施与实施方案,目标是提高学生解决复杂工程问题的能力。
Out-of-Hospital Cardiac Arrest Protocol Comparison
Authors: Perry Omer , Wacht Oren , Jaffe Eli , Sinuany-Stern Zilla , Bitan Yuval
Published: September 2019

Background

Early identification of out-of-hospital cardiac arrest (OHCA) has been proven to increase survival rates. Toward this goal, emergency medical dispatchers commonly use one of two types of emergency medical dispatcher systems, each with a unique OHCA protocol. The criteria-based dispatch (CBD) protocol is a set of guidelines and prompts intended for dispatchers with clinical background and experience, while the medical priority dispatch (MPD) is a scripted caller interrogation protocol intended for non-healthcare dispatchers. The objective of this study was to compare CBD and MPD protocols in terms of accuracy and duration of the identification process.

Methods

To compare the two protocols we conducted an OHCA simulation of an emergency phone call by a bystander. Two groups participated in the simulation: 1) emergency medical technicians during paramedic vocational training, in the role of CBD dispatchers, and 2) non-healthcare personnel in the role of MPD dispatchers. Dispatchers were asked to identify whether a patient was having a cardiac arrest based on the information they received from the bystander.

Results

Duration of the OHCA identification process was significantly shorter for participants using MPD (CBD 50 seconds vs. MPD 33 seconds, p=0.003). The OHCA accuracy was 86.49% for the CBD and 82.86% for MPD, but this difference was not statistically significant (p=0.60).

Conclusion

The advantages of each protocol suggest that some combination of the two protocols may optimise the OHCA identification process, leading to increased accuracy and shorter duration of the identification process.
The Role of Knowledge Adoptive Capacity towards Exports Performance
Authors: Aqdas Ramaisa , Nik Abdullah Nik Ab Halim
Published: September 2019

Purpose - Knowledge absorptive capacity plays a significant role in export performance. It is a dynamic capability that firms apply to gain competitiveness in today’s knowledge-based economies. The aim of the present research is to identify relationship among dimensions of KAC and export performance. Design/Methodology - Nature of study was descriptive and quantitative. Data was collected through questionnaires from 291 large scale textile firms of Pakistan. Smart PLS was used in analyzing data by incorporating CFA and SEM techniques to test the hypotheses. Findings - The results reveal that knowledge acquisition, transformation, and exploitation have significant positive relationship with export performance.
Contribuciones para la Evaluación de la Vulnerabilidad Sísmica de Puentes Típicos en Argentina en cercanía de Fallas Activas
Authors: Aníbal Saracho José , Pérez Gustavo Ariel , Barlek José Rodolfo , Dip Óscar , Castelli Eduardo Alberto
Published: September 2019

La evaluación de la vulnerabilidad sísmica de puentes permite identificar aquellas estructuras sísmicamente deficientes y establecer prioridades y pautas relacionadas con la necesidad de su rehabilitación, refuerzo o reemplazo. Al respecto, en Argentina no existe ninguna metodología establecida. El objetivo es presentar un método de avanzada aplicado a dos puentes típicos ubicados en zonas caracterizadas como de elevada y muy elevada peligrosidad sísmica del territorio nacional a fin de verificar su nivel de desempeño estructural. Se utiliza análisis dinámico no lineal, método considerado como el de mayor rigurosidad. Los modelos 3D utilizados se construyeron con la plataforma de elementos finitos OpenSees. Se verificó el mejor comportamiento sismorresistente del puente que presenta mayor rigidez del sistema suelo de relleno-pilotes en los estribos y con mayor número y robustez de las pilas. Ambos puentes cumplen con los niveles de desempeño exigidos, acorde a la vida útil remanente de cada uno de ellos.
Moving Beyond the Host: Unraveling the Skin Microbiome of Endangered Costa Rican Amphibians
Authors: Jiménez Randall R. , Alvarado Gilbert , Estrella Josimar , Sommer Simone
Published: September 2019

Some neotropical amphibians, including a few species in Costa Rica, were presumed to be “extinct” after dramatic population declines in the late 1980s but have been rediscovered in isolated populations. Such populations seem to have evolved a resistance/tolerance to Batrachochytrium dendrobatidis (Bd), a fungal pathogen that causes a deadly skin disease and is considered one of the main drivers of worldwide amphibian declines. The skin microbiome is an important component of the host’s innate immune system and is associated with Bd-resistance. However, the way that the bacterial diversity of the skin microbiome confers protection against Bd in surviving species remains unclear. We studied variation in the skin microbiome and the prevalence of putatively anti-Bd bacterial taxa in four co-habiting species in the highlands of the Juan Castro Blanco National Park in Costa Rica using 16S rRNA amplicon sequencing. Lithobates vibicarius, Craugastor escoces, and Isthmohyla rivularis have recently been rediscovered, whereas Isthmohyla pseudopuma has suffered population fluctuations but has never disappeared. To investigate the life stage at which the protective skin microbiome is shaped and when shifts occur in the diversity of putatively anti-Bd bacteria, we studied the skin microbiome of tadpoles, juveniles and adults of L. vibicarius. We show that the skin bacterial composition of sympatric species and hosts with distinct Bd-infection statuses differs at the phyla, family, and genus level. We detected 94 amplicon sequence variants (ASVs) with putative anti-Bd activity pertaining to distinct bacterial taxa, e.g., Pseudomonas spp., Acinetobacter johnsonii, and Stenotrophomonas maltophilia. Bd-uninfected L. vibicarius harbored 79% more putatively anti-Bd ASVs than Bd-infected individuals. Although microbiome composition and structure differed across life stages, the diversity of putative anti-Bd bacteria was similar between pre- and post-metamorphic stages of L. vibicarius. Despite low sample size, our results support the idea that the skin microbiome is dynamic and protects against ongoing Bd presence in endangered species persisting after their presumed extinction. Our study serves as a baseline to understand the microbial patterns in species of high conservation value. Identification of microbial signatures linked to variation in disease susceptibility might, therefore, inform mitigation strategies for combating the global decline of amphibians.
Dot Product Equality Constrained Attitude Determination from Two Vector Observations: Theory and Astronautical Applications
Authors: Wu Jin , Shan Shangqiu
Published: September 2019

In this paper, the attitude determination problem from two vector observations is revisited, incorporating the redundant equality constraint obtained by the dot product of vector observations. Analytical solutions to this constrained attitude determination problem are derived. It is found out that the studied two-vector attitude determination problem by Davenport q-method under the dot product constraint has deterministic maximum eigenvalue, which leads to its advantage in error/perturbation analysis and covariance determination. The proposed dot product constrained two-vector attitude solution is applied then to solve several engineering problems. Detailed simulations on spacecrafts attitude determination indicate the efficiency of the proposed theory.
Global Internet Data on the Interest in Antibiotics and Probiotics Generated by Google Trends
Authors: Kamiński Mikołaj , Łoniewski Igor , Marlicz Wojciech
Published: September 2019

Data from the Google search engine enables the assessment of Google users’ interest in a specific topic. We analyzed the world trends in searches associated with the topics “antibiotics” and “probiotics” from January 2004 to June 2019, using Google Trends. We analyzed the yearly trends and seasonal variation. We performed an R-Spearman rank correlation analysis of the relative search volume (RSV) of the topics in 2015 with antibiotic consumption, health expenditure per capita, and the 2015 Human Development Index (HDI) of the country. The mean interest in the topic of antibiotics was equal to RSV = 57.5 ± 17.9, rising by 3.7 RSV/year (6.5%/year), while that of probiotics was RSV = 14.1 ± 7.9, which rose by 1.7 RSV/year (12.1%). The seasonal amplitude of antibiotics was equal to RSV = 9.8, while probiotics was RSV = 2.7. The seasonal peaks for both topics were observed in the cold months. The RSV of probiotics, but not antibiotics, was associated with antibiotic consumption (Rs = 0.35; p < 0.01), health expenditure (Rs = 0.41; p < 0.001), and HDI (Rs = 0.44; p < 0.001). Google users’ interest in antibiotic- and probiotic-related information increases from year to year, and peaks in cold months. The interest in probiotic-related information might be associated with antibiotic consumption, health expenditure, and the development status of the Google users’ country.
Investigation of Electrodeposition External Conditions on Morphology and Texture of Ni/SiCw Composite Coatings
Authors: Lai Liyan , Li Hongfang , Sun Yunna , Ding Guifu , Wang Hong , Yang Zhuoqing
Published: September 2019

Recently, a strategy of synthesizing SiC whisker-reinforced nickel (Ni/SiCw) composites with excellent mechanical properties by electrodeposition has been proposed for exploring its potential applications in micromechanical devices. In this paper, a series of external conditions that affected the content of SiC whiskers in composite films were studied, such as cathode current density, stirring rate and electrolyte temperature. The experimental results indicated that the optimum morphology was obtained at a stirring speed of 300 rpm, a temperature of 50 °C, and a current density of 18 mA/cm2. Additionally, the content of SiC whiskers and textural preference were also investigated by varying its external conditions, and the results demonstrated that the composites with high mass percentage whiskers are more advantageous for electrocrystallization of Ni in the (200) orientation. Finally, the relationship between external conditions and intrinsic morphology, composition and texture of Ni/SiCw composites was revealed, and it provides a constructive approach to fabricate the high-content SiC whiskers of these composites.
Biological Effects of High-Voltage Electric Field Treatment of Naked Oat Seeds
Authors: Xu Wenqian , Song Zhiqing , Luan Xinyu , Ding Changjiang , Cao Zhiyuan , Ma Xiaohong
Published: September 2019

In order to study the mechanism of high-voltage electric field (HVEF) biotechnology, corona discharge produced by a multi-needle-plate HVEF was used to treat naked oat seeds, each treatment dose was divided into two groups, one group was covered with a petri dish cover, the other group was directly exposed to HVEF without a petri dish cover. The scanning electron microscope (SEM) results show that the etching degree of the uncovered group was more serious than that of the covered group, it indicates that ion wind etching has a greater impact on the micro-morphology of seed coat, being covered can effectively reduce the etching degree of discharge plasma on seed. Fourier Transform infrared spectroscopy (FTIR) of the seed coat shows most of the HVEF treatment group can form a new absorption peak at 1740 cm−1, which is closely related to the hydrophilicity of the seed. Comprehensive analysis shows that HVEF treatment can improve the hydrophilicity of seeds, whether they are covered or not. Being covered can reduce the degree of etching of the seed coat, but increase the hydrophilicity of the seed, indicating that the non-uniform electric field has a greater impact on the hydrophilicity of the seed. Our study showed that ion wind had an effect on the micro-morphology of seeds, but this effect didn’t translate into a macroscopic effect. This study provides ideas and experimental data support for the study of the biotechnological mechanism of HVEF.
The Effect of Sonication on Bubble Size and Sensory Perception of Carbonated Water to Improve Quality and Consumer Acceptability
Authors: Viejo Claudia Gonzalez , Torrico Damir D. , Dunshea Frank R. , Fuentes Sigfredo
Published: September 2019

Bubbles are important for carbonated beverage quality since smaller bubbles contribute to higher acceptability. Therefore, the effects and acceptability of the application of audible sound in carbonated water were studied using three brands and applying five frequencies for one minute each in ascending order. Six samples, two from each brand, were used for treatments: (i) control and (ii) sonication. Physicochemical measurements consisted of total dissolved solids (TDS), electric conductivity (EC), pH, bubble size, and bubble size distribution. A sensory session (N = 30) was conducted using the Bio-Sensory application to assess acceptability and emotions using self-reported and biometric responses. Statistical analysis included: ANOVA (α = 0.05) and principal component analysis (PCA) for quantitative data and Cochran Q test with pairwise comparisons (p < 0.05) for self-reported emotion responses. Results showed that the sonication effect for the sample with higher TDS, EC, and pH (SPS) reduced bubble size by 46%, while in those with lowest TDS, EC, and pH (IceS) caused an increase of 158% compared to the control. For samples with intermediate values (NuS), there were non-significant differences (p > 0.05) compared to the control. Acceptability was higher for samples with sonication for the three brands. Emotional self-reported responses were more positive for samples with sonication, showing significant differences (p < 0.05) for emotions such as “happy” and “pleased” during both sound and visual assessments. From PCA, a positive relationship between bubble size and liking of bubbles was found as well as for the number of medium bubbles and happy facial expression. The audible sound generated by ubiquitous sound systems may potentially be used by the industry, applying it to the bottled product to modify bubble size and improve quality and acceptability of carbonated beverages.
Recent Advances in the Use of Polyhydroyalkanoates in Biomedicine
Authors: Rodriguez-Contreras Alejandra
Published: September 2019

Polyhydroxyalkanoates (PHAs), a family of natural biopolyesters, are widely used in many applications, especially in biomedicine. Since they are produced by a variety of microorganisms, they possess special properties that synthetic polyesters do not have. Their biocompatibility, biodegradability, and non-toxicity are the crucial properties that make these biologically produced thermoplastics and elastomers suitable for their applications as biomaterials. Bacterial or archaeal fermentation by the combination of different carbohydrates or by the addition of specific inductors allows the bioproduction of a great variety of members from the PHAs family with diverse material properties. Poly(3-hydroxybutyrate) (PHB) and its copolymers, such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHVB) or poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (PHB4HB), are the most frequently used PHAs in the field of biomedicine. PHAs have been used in implantology as sutures and valves, in tissue engineering as bone graft substitutes, cartilage, stents for nerve repair, and cardiovascular patches. Due to their good biodegradability in the body and their breakdown products being unhazardous, they have also been remarkably applied as drug carriers for delivery systems. As lately there has been considerable and growing interest in the use of PHAs as biomaterials and their application in the field of medicine, this review provides an insight into the most recent scientific studies and advances in PHAs exploitation in biomedicine.
Assessment of Antioxidant and Cytotoxic Activities of Extracts of Dendrobium crepidatum
Authors: Paudel Mukti Ram , Chand Mukesh Babu , Pant Basant , Pant Bijaya
Published: September 2019

Dendrobium crepidatum is an epiphytic orchid found in south Asia including Nepal and China. This orchid species is widely used in traditional Chinese medicine (TCM) for the treatment of cancer, diabetes, cataracts, and fever. The objectives of the present research were to assess the antioxidant and cytotoxic properties of its stem’s extracts with the identification of bioactive secondary metabolites. The antioxidant and cytotoxic activities were evaluated using the DPPH (2,2-diphenyl-1-picrylhydrazyl) and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, respectively, and compounds were identified using GC–MS (gas chromatography and mass spectrometry). Ethanol and acetone extracts scavenged 94.69 ± 0.10% and 93.41 ± 0.86% of DPPH free radicals, respectively. They showed 50% inhibition of DPPH free radicals (IC50) at concentrations of 73.90 µg/mL and 99.44 µg/mL, which were found to be statistically similar to that of ascorbic acid (control). Chloroform extract inhibited the growth of 81.49 ± 0.43% of HeLa (human cervical carcinoma) cells and hexane extract inhibited the growth of 76.45 ± 4.26% of U251 (human glioblastoma) cells at 800 µg/mL concentration. These extracts showed 50% inhibition of cell growth (IC50) toward both the HeLa and U251 cell lines at their high concentrations, which were found statistically significantly different from that of cisplatin drug (control). The above extracts showed antioxidant and cytotoxic properties, potentially due to the presence of tetracosane, triacontane, stigmasterol, and some phenol derivatives (2-methoxy-4-vinylphenol, 2-methoxy-5-(1-propenyl)-phenol, p-mesyloxyphenol, and 2,6-dimethoxy-4-(2-propenyl)-phenol). This study explores the potential of this orchid in alternative medicine toward the development of drugs from its medicinally active compounds.
Large-Scale Production of Bioactive Terrein by Aspergillus terreus Strain S020 Isolated from the Saudi Coast of the Red Sea
Authors: Asfour Hani Z. , Awan Zuhier A. , Bagalagel Alaa A. , Elfaky Mahmoud A. , Abdelhameed Reda F. A. , Elhady Sameh S.
Published: September 2019

The diversity of symbiotic fungi derived from two marine sponges and sediment collected off Obhur, Jeddah (Saudi Arabia), was investigated in the current study. A total of 23 isolates were purified using a culture-dependent approach. Using the morphological properties combined with internal transcribed spacer-rDNA (ITS-rDNA) sequences, 23 fungal strains (in the majority Penicillium and Aspergillus) were identified from these samples. The biological screening (cytotoxic and antimicrobial activities) of small-scale cultures of these fungi yielded several target fungal strains which produced bioactive secondary metabolites. Amongst these isolates, the crude extract of Aspergillus terreus strain S020, which was cultured in fermentation static broth, 21 L, for 40 days at room temperature on potato dextrose broth, displayed strong antimicrobial activities against Pseudomonas aeruginosa and Staphylococcus aureus and significant antiproliferative effects on human carcinoma cells. Chromatographic separation of the crude extract by silica gel column chromatography indicated that the S020 isolate could produce a series of chemical compounds. Among these, pure crystalline terrein was separated with a high yield of 537.26 ± 23.42 g/kg extract, which represents the highest fermentation production of terrein to date. Its chemical structure was elucidated on the basis of high-resolution electrospray ionization mass spectrometry (HRESIMS) or high-resolution mass spectrometry (HRMS), 1D, and 2D NMR spectroscopic analyses and by comparison with reported data. The compound showed strong cytotoxic activity against colorectal carcinoma cells (HCT-116) and hepatocellular carcinoma cells (HepG2), with IC50 values of 12.13 and 22.53 µM, respectively. Our study highlights the potential of A. terreus strain S020 for the industrial production of bioactive terrein on a large scale and the importance of future investigations of these strains to identify the bioactive leads in these fungal extracts.
Quercetin Interrupts the Positive Feedback Loop Between STAT3 and IL-6, Promotes Autophagy, and Reduces ROS, Preventing EBV-Driven B Cell Immortalization
Authors: Granato Marisa , Gilardini Montani Maria Saveria , Zompetta Claudia , Santarelli Roberta , Gonnella Roberta , Romeo Maria Anele , D’Orazi Gabriella , Faggioni Alberto , Cirone Mara
Published: September 2019

The oncogenic gammaherpesvirus Epstein–Barr virus (EBV) immortalizes in vitro B lymphocytes into lymphoblastoid cell lines (LCLs), a model that gives the opportunity to explore the molecular mechanisms driving viral tumorigenesis. In this study, we addressed the potential of quercetin, a widely distributed flavonoid displaying antioxidant, anti-inflammatory, and anti-cancer properties, in preventing EBV-driven B cell immortalization. The results obtained indicated that quercetin inhibited thectivation of signal transducer and activator of transcription 3 (STAT3) induced by EBV infection and reduced molecules such as interleukin-6 (IL-6) and reactive oxidative species (ROS) known to be essential for the immortalization process. Moreover, we found that quercetin promoted autophagy and counteracted the accumulation of sequestosome1/p62 (SQSTM1/p62), ultimately leading to the prevention of B cell immortalization. These findings suggest that quercetin may have the potential to be used to counteract EBV-driven lymphomagenesis, especially if its stability is improved.
Insights into Ergosterol Peroxide’s Trypanocidal Activity
Authors: Meza-Menchaca Thuluz , Ramos-Ligonio Angel , López-Monteon Aracely , Vidal Limón Abraham , Kaluzhskiy Leonid , V. Shkel Tatjana , V. Strushkevich Natallia , Jiménez-García Luis , Agredano Moreno Lourdes , Gallegos-García Verónica , Suárez-Medellín Jorge , Trigos Ángel
Published: September 2019

Trypanosoma cruzi, which causes Chagas disease, is a significant health threat in many countries and affects millions of people. Given the magnitude of this disease, a broader understanding of trypanocidal mechanisms is needed to prevent and treat infection. Natural endoperoxides, such as ergosterol peroxide, have been shown to be toxic to parasites without causing harm to human cells or tissues. Although prior studies have demonstrated the trypanocidal activity of ergosterol peroxide, the cellular and molecular mechanisms remain unknown. The results of this study indicate that a free-radical reaction occurs in T. cruzi following ergosterol peroxide exposure, leading to cell death. Using a combination of biochemical, microscopic and in silico experimental approaches, we have identified, for the first time, the cellular and molecular cytotoxic mechanism of an ergosterol peroxide obtained from Pleurotus ostreatus (Jacq) P. Kumm. f. sp. Florida.
Long-chain Omega-3 Polyunsaturated Fatty Acids in Natural Ecosystems and the Human Diet: Assumptions and Challenges
Authors: Gladyshev Michail I. , Sushchik Nadezhda N.
Published: September 2019

Over the past three decades, studies of essential biomolecules, long-chain polyunsaturated fatty acids of the omega-3 family (LC-PUFAs), namely eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have made considerable progress, resulting in several important assumptions. However, new data, which continue to appear, challenge these assumptions. Based on the current literature, an attempt is made to reconsider the following assumptions: 1. There are algal classes of high and low nutritive quality. 2. EPA and DHA decrease with increasing eutrophication in aquatic ecosystems. 3. Animals need EPA and DHA. 4. Fish are the main food source of EPA and DHA for humans. 5. Culinary treatment decreases EPA and DHA in products. As demonstrated, some of the above assumptions need to be substantially specified and changed.
Fetal Brain Abnormality Classification from MRI Images of Different Gestational Age
Authors: Attallah Omneya , Sharkas Maha A. , Gadelkarim Heba
Published: September 2019

Magnetic resonance imaging (MRI) is a common imaging technique used extensively to study human brain activities. Recently, it has been used for scanning the fetal brain. Amongst 1000 pregnant women, 3 of them have fetuses with brain abnormality. Hence, the primary detection and classification are important. Machine learning techniques have a large potential in aiding the early detection of these abnormalities, which correspondingly could enhance the diagnosis process and follow up plans. Most research focused on the classification of abnormal brains in a primary age has been for newborns and premature infants, with fewer studies focusing on images for fetuses. These studies associated fetal scans to scans after birth for the detection and classification of brain defects early in the neonatal age. This type of brain abnormality is named small for gestational age (SGA). This article proposes a novel framework for the classification of fetal brains at an early age (before the fetus is born). As far as we could know, this is the first study to classify brain abnormalities of fetuses of widespread gestational ages (GAs). The study incorporates several machine learning classifiers, such as diagonal quadratic discriminates analysis (DQDA), K-nearest neighbour (K-NN), random forest, naïve Bayes, and radial basis function (RBF) neural network classifiers. Moreover, several bagging and Adaboosting ensembles models have been constructed using random forest, naïve Bayes, and RBF network classifiers. The performances of these ensembles have been compared with their individual models. Our results show that our novel approach can successfully identify and classify numerous types of defects within MRI images of the fetal brain of various GAs. Using the KNN classifier, we were able to achieve the highest classification accuracy and area under receiving operating characteristics of 95.6% and 99% respectively. In addition, ensemble classifiers improved the results of their respective individual models.
Targeting Autophagy by MPT0L145, a Highly Potent PIK3C3 Inhibitor, Provides Synergistic Interaction to Targeted or Chemotherapeutic Agents in Cancer Cells
Authors: Chen Chun-Han , Hsieh Tsung-Han , Lin Yu-Chen , Liu Yun-Ru , Liou Jing-Ping , Yen Yun
Published: September 2019

Anticancer therapies reportedly promote pro-survival autophagy in cancer cells that confers drug resistance, rationalizing the concept to combine autophagy inhibitors to increase their therapeutic potential. We previously identified that MPT0L145 is a PIK3C3/FGFR inhibitor that not only increases autophagosome formation due to fibroblast growth factor receptor (FGFR) inhibition but also perturbs autophagic flux via PIK3C3 inhibition in bladder cancer cells harboring FGFR activation. In this study, we hypothesized that combined-use of MPT0L145 with agents that induce pro-survival autophagy may provide synthetic lethality in cancer cells without FGFR activation. The results showed that MPT0L145 synergistically sensitizes anticancer effects of gefitinib and gemcitabine in non-small cell lung cancer A549 cells and pancreatic cancer PANC-1 cells, respectively. Mechanistically, drug combination increased incomplete autophagy due to impaired PIK3C3 function by MPT0L145 as evidenced by p62 accumulation and no additional apoptotic cell death was observed. Meanwhile, drug combination perturbed survival pathways and increased vacuolization and ROS production in cancer cells. In conclusion, the data suggest that halting pro-survival autophagy by targeting PIK3C3 with MPT0L145 significantly sensitizes cancer cells to targeted or chemotherapeutic agents, fostering rational combination strategies for cancer therapy in the future.
Early Steps of Mammary Stem Cell Transformation by Exogenous Signals; Effects of Bisphenol Endocrine Disrupting Chemicals and Bone Morphogenetic Proteins
Authors: Jung Nora , Maguer-Satta Veronique , Guyot Boris
Published: September 2019

Estrogens are major regulators of the mammary gland development, notably during puberty, via estrogen receptor (ER) activation, leading to the proliferation and differentiation of mammary cells. In addition to estrogens, the bone morphogenetic proteins (BMPs) family is involved in breast stem cell/progenitor commitment. However, these two pathways that synergistically contribute to the biology of the normal mammary gland have also been described to initiate and/or promote breast cancer development. In addition to intrinsic events, lifestyle habits and exposure to environmental cues are key risk factors for cancer in general, and especially for breast cancer. In the latter case, bisphenol A (BPA), an estrogen-mimetic compound, is a critical pollutant both in terms of the quantities released in our environment and of its known and speculated effects on mammary gland biology. In this review, we summarize the current knowledge on the actions of BMPs and estrogens in both normal mammary gland development and breast cancer initiation, dissemination, and resistance to treatment, focusing on the dysregulations of these processes by BPA but also by other bisphenols, including BPS and BPF, initially considered as safer alternatives to BPA.
Low Numbers of Vascular Vessels Correlate to Progression in Hormone-Naïve Prostate Carcinomas Undergoing Radical Prostatectomy
Authors: Smentoch Julia , Szade Jolanta , Żaczek Anna J. , Eltze Elke , Semjonow Axel , Brandt Burkhard , Bednarz-Knoll Natalia
Published: September 2019

Vascularization influences tumor development by supporting the nutrition and dissemination of tumor cells. On the other hand, a low number of vascular vessels (VVlow) may induce hypoxia, accounting for selection of resistant clone(s) of tumor cells. This study aimed to evaluate the prognostic significance of vascular (VV) and lymphatic vessels (LV) in prostate cancer (PCa). Tumor samples from 400 PCa patients undergoing radical prostatectomy (RP) were prepared in duplex as tissue microarrays. Numbers of VV and LV were evaluated using immunohistochemistry detecting CD34 and podoplanin, respectively, and correlated to clinical data, biochemical recurrence (BR), and proteins analyzed in tumor cells. VVlow and LV were found in 32% and 43% of patients with informative PCa samples, respectively. VVlow correlated with a shorter time to BR 3, 5, and 10 years after RP in hormone-naïve patients (p = 0.028, p = 0.027 and p = 0.056, respectively). It was also shown to be an independent prognostic factor 5 years after surgery (multivariate analysis, p = 0.046). Tumors characterized by VVlow expressed the epithelial cell adhesion molecule, EpCAM, less frequently (p = 0.016) and revealed a borderline correlation to increased levels of tumor cell invasion marker Loxl-2 (p = 0.059). No correlations were found for LV. In summary, VVlow in hormone-naïve patients undergoing RP has prognostic potential and seems to be related to an aggressive phenotype of tumor cells.
Kinase Inhibitors and Ovarian Cancer
Authors: Katopodis Periklis , Chudasama Dimple , Wander Gurleen , Sales Louise , Kumar Juhi , Pandhal Manreen , Anikin Vladimir , Chatterjee Jayanta , Hall Marcia , Karteris Emmanouil
Published: September 2019

Ovarian cancer is fifth in the rankings of cancer deaths among women, and accounts for more deaths than any other gynecological malignancy. Despite some improvement in overall-(OS) and progression-free survival (PFS) following surgery and first-line chemotherapy, there is a need for development of novel and more effective therapeutic strategies. In this mini review, we provide a summary of the current landscape of the clinical use of tyrosine kinase inhibitors (TKIs) and mechanistic target of rapamycin (mTOR) inhibitors in ovarian cancer. Emerging data from phase I and II trials reveals that a combinatorial treatment that includes TKIs and chemotherapy agents seems promising in terms of PFS despite some adverse effects recorded; whereas the use of mTOR inhibitors seems less effective. There is a need for further research into the inhibition of multiple signaling pathways in ovarian cancer and progression to phase III trials for drugs that seem most promising.
Catalytic, Photocatalytic, and Electrocatalytic Processes for the Valorization of CO2
Authors: Rossetti Ilenia , Ramis Gianguido
Published: September 2019

Worldwide yearly CO2 emissions reached 36 Gt in 2014, whereas they amounted to ca [...]
Designing a Mesoporous Zeolite Catalyst for Products Optimizing in n-Decane Hydrocraking
Authors: Tan Li , Guo Xiaoyu , Gao Xinhua , Tsubaki Noritatsu
Published: September 2019

Mesoporous ZSM-5 zeolite is developed to enhance the catalytic performance in a hydrocracking reaction. The generated mesopores and mesoporous channels in the new catalyst supply more opportunities for reactant accessing the active sites according to the better mass transfer and diffusion. Meanwhile, the acidity of the mesoporous catalyst is also weakened because of the removal of Si and Al species from its MFI structure, which makes the products distribution drift to more valued chemicals such as olefins. In the modified mesoporous ZSM-5 zeolites via different metallic promoters, the olefins’ selectivity increases as the alkalinity of the catalyst increases. The reason for this is that the formed olefins will be further hydrogenated into corresponding alkanes immediately over the extremely acidic zeolite catalyst. Hence, the moderate alkalinity will limit this process, while at the same time the remaining olefins products will too. Furthermore, the Pd-based mesoporous ZSM-5 zeolite shows an excellent n-decane conversion and high propane selectivity due to the occurrence of hydrogen spillover via the Pd promoter. The phenomenon of hydrogen spillover supplies more chemisorbed sites of hydrogen atoms for hydrocracking and hydrogenating in this reaction. In short, this study explores the important effect factors in n-decane hydrocracking reaction activity and products distribution. It also shows a potential for the further industrial application of petroleum-derived fuel hydrocracking according to the optimized products distribution under metallic promoted mesoporous zeolite.
Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism
Authors: Fan Yuxiang , Simmen Thomas
Published: September 2019

The past decade has seen the emergence of endoplasmic reticulum (ER) chaperones as key determinants of contact formation between mitochondria and the ER on the mitochondria-associated membrane (MAM). Despite the known roles of ER–mitochondria tethering factors like PACS-2 and mitofusin-2, it is not yet entirely clear how they mechanistically interact with the ER environment to determine mitochondrial metabolism. In this article, we review the mechanisms used to communicate ER redox and folding conditions to the mitochondria, presumably with the goal of controlling mitochondrial metabolism at the Krebs cycle and at the electron transport chain, leading to oxidative phosphorylation (OXPHOS). To achieve this goal, redox nanodomains in the ER and the interorganellar cleft influence the activities of ER chaperones and Ca2+-handling proteins to signal to mitochondria. This mechanism, based on ER chaperones like calnexin and ER oxidoreductases like Ero1α, controls reactive oxygen production within the ER, which can chemically modify the proteins controlling ER–mitochondria tethering, or mitochondrial membrane dynamics. It can also lead to the expression of apoptotic or metabolic transcription factors. The link between mitochondrial metabolism and ER homeostasis is evident from the specific functions of mitochondria–ER contact site (MERC)-localized Ire1 and PERK. These functions allow these two transmembrane proteins to act as mitochondria-preserving guardians, a function that is apparently unrelated to their functions in the unfolded protein response (UPR). In scenarios where ER stress cannot be resolved via the activation of mitochondrial OXPHOS, MAM-localized autophagosome formation acts to remove defective portions of the ER. ER chaperones such as calnexin are again critical regulators of this MERC readout.
splitGFP Technology Reveals Dose-Dependent ER-Mitochondria Interface Modulation by α-Synuclein A53T and A30P Mutants
Authors: Calì Tito , Ottolini Denis , Vicario Mattia , Catoni Cristina , Vallese Francesca , Cieri Domenico , Barazzuol Lucia , Brini Marisa
Published: September 2019

Familial Parkinson’s disease (PD) is associated with duplication or mutations of α-synuclein gene, whose product is a presynaptic cytosolic protein also found in mitochondria and in mitochondrial-associated ER membranes. We have originally shown the role of α-syn as a modulator of the ER-mitochondria interface and mitochondrial Ca2+ transients, suggesting that, at mild levels of expression, α-syn sustains cell metabolism. Here, we investigated the possibility that α-syn action on ER-mitochondria tethering could be compromised by the presence of PD-related mutations. The clarification of this aspect could contribute to elucidate key mechanisms underlying PD. The findings reported so far are not consistent, possibly because of the different methods used to evaluate ER-mitochondria connectivity. Here, the effects of the PD-related α-syn mutations A53T and A30P on ER-mitochondria relationship were investigated in respect to Ca2+ handling and mitochondrial function using a newly generated SPLICS sensor and aequorin-based Ca2+measurements. We provided evidence that A53T and A30P amino acid substitution does not affect the ability of α-syn to enhance ER/mitochondria tethering and mitochondrial Ca2+ transients, but that this action was lost as soon as a high amount of TAT-delivered A53T and A30P α-syn mutants caused the redistribution of α-syn from cytoplasm to foci. Our results suggest a loss of function mechanism and highlight a possible connection between α-syn and ER-mitochondria Ca2+ cross-talk impairment to the pathogenesis of PD.
Progress in the Analysis of Food Allergens through Molecular Biology Approaches
Authors: Volpicella Mariateresa , Leoni Claudia , Dileo Maria C.G. , Ceci Luigi R.
Published: September 2019

Food allergies associated with class E immunoglobulins (IgE) are a serious health problem that affects between 1% and 10% of the population of developing countries, with a variability that depends on the geographical area and age range considered. These allergies are caused by a cross-link reaction between a specific food protein (the allergen) and the host IgE. Allergic reactions can range from mild itching to anaphylactic shock and there are no clues to predict the effects of an allergen. Strict avoidance of allergenic food is the only way to avoid possible serious allergic reactions. In the last 30 years a growing number of molecular studies have been conducted to obtain information on the diffusion of food allergens and to establish the structural basis of their allergenicity. At the same time, these studies have also allowed the development of molecular tools (mainly based on synthetic peptides and recombinant allergens) that can be of great help for diagnostic and therapeutic approaches of food allergies. Accordingly, this review focuses on advances in the study of food allergens made possible by molecular technologies and how results and technologies can be integrated for the development of a systematic food molecular allergology. The review may be of interest both to scientists approaching this field of investigation and to physicians who wish to have an update on the progress of research in diagnosis and therapy of food allergies.
Hyaluronan Accelerates Intestinal Mucosal Healing through Interaction with TSG-6
Authors: Sammarco Giusy , Shalaby Mohammad , Elangovan Sudharshan , Petti Luciana , Roda Giulia , Restelli Silvia , Arena Vincenzo , Ungaro Federica , Fiorino Gionata , Day Anthony J. , D’Alessio Silvia , Vetrano Stefania
Published: September 2019

Hyaluronan (HA) has proven to be beneficial in the treatment of several diseases. Recently, it has been shown that the local application of HA (IBD98E) improves endoscopic and clinical outcomes in subjects with active distal ulcerative colitis (UC). However, the mechanisms by which this polysaccharide exerts its beneficial effects are unclear. Here, we demonstrated that HA treatment in vitro and in vivo improved mucosal healing by accelerating intestinal epithelial regeneration. Indeed, mice treated with HA showed a faster recovery from colitis and reduced endoscopic signs of mucosal inflammation compared to those receiving saline. Furthermore, histological analysis revealed less ulcerated mucosa in mice treated with HA, characterized by re-epithelialized areas. TSG-6, the secreted product of TNF-stimulated gene-6, is an HA-binding protein shown previously to have tissue-protective properties and promote wound healing. Mucosal levels of TSG-6 increased in UC patients compared to the healthy controls and also after wounding in mice. TSG-6 deletion prevented the beneficial properties of HA in mucosal wound repair, suggesting that the interaction of HA with TSG-6 is crucial for intestinal epithelial regeneration. Overall these results are consistent with HA having a therapeutic effect via the promotion of mucosal healing in patients with ulcerative colitis.
Stable Isotope Analyses of Multiple Tissues of Great Shearwaters (Ardenna Gravis) Reveals Long-Term Dietary Stability, Short-Term Changes in Diet, and Can be Used as a Tool to Monitor Food Webs
Authors: Hong Peter , Wiley David N. , Powers Kevin D. , Michener Robert H. , Kaufman Les , Hatch Kent A.
Published: September 2019

The great shearwater (Ardenna gravis) is a common pelagic bird with a distribution that spans almost the entire Atlantic basin, which in conjunction with its relatively high abundance, makes great shearwaters an effective bio indicator. We compared δ13C and δ15N values from the feathers, red blood cells (RBCs), and plasma of great shearwaters collected in 2014 and 2015 from the waters off Massachusetts and Cape Cod. The δ13C and δ15N values of RBCs were quite constant between sampling periods and years, suggesting a generally stable food web over that time period. However, the δ13C of plasma indicates a small seasonal change in diet between July and September for both years, with plasma δ15N values suggesting a slight increase in trophic level late in summer. Comparison of the δ15N of RBCs and plasma indicates that great shearwaters experienced a diet shift during the first few weeks of summer 2014, but not in 2015. Comparisons with other studies suggest that these shearwaters feed at a lower trophic level than great shearwaters sampled in the Bay of Fundy and that there is a decrease in δ13C with increasing latitude, which could indicate a more pelagic diet in northern waters. Stable isotope analysis of the sixth primary feathers provided evidence that these feathers are molted in the Northern Hemisphere and that the diet of great shearwaters shortly after arrival was different in 2014 and 2015. This study demonstrates that within species comparisons of tissue isotopic signatures over time and comparisons of isotopic signatures of tissues with different turnover rates, can detect changes in diet and be used as a tool to monitor for changes in marine food webs over time and space. The relevant signals remain informative even in the absence of species-specific data on tissue-diet discrimination factors, tissue turnover rates, or knowledge of dietary components and their stable isotopic signatures, suggesting dietary changes indicative of a corresponding change in the food web.
Effects of Financial Education and Financial Literacy on Creative Entrepreneurship: A Worldwide Research
Authors: Abad-Segura Emilio , González-Zamar Mariana-Daniela
Published: September 2019

The limited attention given to financial education in the development of student competencies can undermine the decision making of individuals in their adulthood. This circumstance has been widely studied in the literature, where the effect of financial literacy on creative entrepreneurship is influenced. The objective of this study is to analyze global research trends on the effect of financial education and financial literacy with the creativity of individual entrepreneurship. For this, a bibliometric analysis was carried out on 665 documents related to the subject of study during 1990–2018 period. The results show the most influential journals, authors, institutions, countries, and areas of knowledge on this scientific research. This work detects the main trends and patterns to offer a vision of the relationship between financial education and creative entrepreneurship. It should be noted that this research area has become a relevant field of study in education, finance, business, and management issues.
Research on In-Vehicle Key Management System under Upcoming Vehicle Network Architecture
Authors: Wu Zhihong , Zhao Jianning , Zhu Yuan , Lu Ke , Shi Fenglue
Published: September 2019

The intelligentization and connectedness of vehicles make vehicle cybersecurity an important research topic. In-vehicle key management is a critical function in vehicle cybersecurity countermeasures. After describing previous research on vehicle key management and the development trend of vehicle network architecture, a key management scheme for in-vehicle multi-layer electronic control units (ECUs) is proposed. The scheme is based on authenticated key exchange protocol 2 (AKEP2) and on-the-air (OTA) technology. Then, the key storage and trusted key usage based on secure hardware are analyzed and studied. Moreover, the AES Counter with CBC-MAC (AES-CCM) algorithm, which uses fewer keys, is introduced to in-vehicle secure communication. The simulation analysis for the proposed OTA-based key update protocol verifies the protocol’s security. The validity of the hardware-based trusted key usage environment and the feasibility of the AES-CCM algorithm for the CAN FD bus are proven with corresponding experiments.
Hierarchical Control with Fast Primary Control for Multiple Single-Phase Electric Springs
Authors: Wang Qingsong , Zuo Wujian , Cheng Ming , Deng Fujin , Buja Giuseppe
Published: September 2019

An electric spring (ES) is a new power compensation device which becomes useful for the large-scale integration of renewable energy sources into the grid. However, when the grid contains two or more ESs connected at different nodes, a voltage drop occurs between the nodes due to the line impedance. Therefore, the voltage of the ES-stabilized nodes cannot be set at the same reference (e.g., 220 V), otherwise one or more ESs break away because of the voltage windup. In this paper, a hierarchical control of multiple ESs tied to a microgrid is proposed to account for the line voltage drop. The primary control relies on the power decoupling control; it is designed for islanded operation of the microgrid, which improves the dynamics of both the voltage and frequency regulation. The secondary control relies on the droop control; it is introduced to coordinate the operation of the ESs by modifying the reference voltage of each ES dynamically. Advantages and disadvantages of the proposed hierarchical control are analyzed together with the explanations of the algorithms developed for its realization. At last, effectiveness of the arranged control system is validated by simulations on the MATLAB/Simulink platform.