bluuebunny/crossref_metadata_2025 huggingface dataset:
Micromanagement of Developmental and Stress-Induced Senescence: The Emerging Role of MicroRNAs
Authors: Swida-Barteczka Aleksandra , Szweykowska-Kulinska Zofia
Published: March 2019

MicroRNAs are short (19–24-nucleotide-long), non-coding RNA molecules. They downregulate gene expression by triggering the cleavage or translational inhibition of complementary mRNAs. Senescence is a stage of development following growth completion and is dependent on the expression of specific genes. MicroRNAs control the gene expression responsible for plant competence to answer senescence signals. Therefore, they coordinate the juvenile-to-adult phase transition of the whole plant, the growth and senescence phase of each leaf, age-related cellular structure changes during vessel formation, and remobilization of resources occurring during senescence. MicroRNAs are also engaged in the ripening and postharvest senescence of agronomically important fruits. Moreover, the hormonal regulation of senescence requires microRNA contribution. Environmental cues, such as darkness or drought, induce senescence-like processes in which microRNAs also play regulatory roles. In this review, we discuss recent findings concerning the role of microRNAs in the senescence of various plant species.
Overexpression of Two Members of D7 Salivary Genes Family is Associated with Pyrethroid Resistance in the Malaria Vector Anopheles Funestus s.s. but Not in Anopheles Gambiae in Cameroon
Authors: Elanga-Ndille Emmanuel , Nouage Lynda , Binyang Achille , Assatse Tatiane , Tene-Fossog Billy , Tchouakui Magellan , Nguete Nguiffo Daniel , Irving Helen , Ndo Cyrille , Awono-Ambene Parfait , Wondji Charles S.
Published: March 2019

D7 family proteins are among the most expressed salivary proteins in mosquitoes. They facilitate blood meal intake of the mosquito by scavenging host amines that induce vasoconstriction, platelet aggregation and pain. Despite this important role, little information is available on the impact of insecticide resistance on the regulation of D7 proteins and consequently on the blood feeding success. In this study, real-time quantitative polymerase chain reaction (qPCR) analyses were performed to investigate how pyrethroid resistance could influence the expression of genes encoding D7 family proteins in Anopheles gambiae and Anopheles funestus s.s. mosquitoes from Elon in the Central Cameroon. Out of 328 collected mosquitoes, 256 were identified as An. funestus sl and 64 as An. gambiae sl. Within the An. funestus group, An. funestus s.s. was the most abundant species (95.95%) with An. rivulorum, An. parensis and An. rivulorum-like also detected. All An. gambiae s.l mosquitoes were identified as An. gambiae. High levels of pyrethroid resistance were observed in both An. gambiae and An. funestus mosquitoes. RT-qPCR analyses revealed a significant overexpression of two genes encoding D7 proteins, D7r3 and D7r4, in pyrethroids resistant An. funestus. However, no association was observed between the polymorphism of these genes and their overexpression. In contrast, overall D7 salivary genes were under-expressed in pyrethroid resistant An. gambiae. This study provides preliminary evidences that pyrethroid resistance could influence blood meal intake through over-expression of D7 proteins although future studies will help establishing potential impact on vectorial capacity.
RNA Sequencing Reveals Specific Transcriptomic Signatures Distinguishing Effects of the [SWI+] Prion and SWI1 Deletion in Yeast Saccharomyces cerevisiae
Authors: Malovichko Yury V. , Antonets Kirill S. , Maslova Anna R. , Andreeva Elena A. , Inge-Vechtomov Sergey G. , Nizhnikov Anton A.
Published: March 2019

Prions are infectious, self-perpetuating protein conformers. In mammals, pathological aggregation of the prion protein causes incurable neurodegenerative disorders, while in yeast Saccharomyces cerevisiae, prion formation may be neutral or even beneficial. According to the prevailing contemporary point of view, prion formation is considered to be a functional inactivation of the corresponding protein whose conformational state shifts from the functional monomeric one to the infectious aggregated one. The Swi1 protein forms the [SWI+] prion and belongs to the nucleosome remodeler complex SWI/SNF controlling the expression of a significant part of the yeast genome. In this work, we performed RNA sequencing of isogenic S. cerevisiae strains grown on the media containing galactose as the sole carbon source. These strains bore the [SWI+] prion or had its structural gene SWI1 deleted. The comparative analysis showed that [SWI+] affects genome expression significantly weaker as compared to the SWI1 deletion. Moreover, in contrast to [SWI+], the SWI1 deletion causes the general inhibition of translation-related genes expression and chromosome I disomy. At the same time, the [SWI+] prion exhibits a specific pattern of modulation of the metabolic pathways and some biological processes and functions, as well as the expression of several genes. Thus, the [SWI+] prion only partially corresponds to the loss-of-function of SWI1 and demonstrates several gain-of-function traits.
Multispectral Multibeam Echo Sounder Backscatter as a Tool for Improved Seafloor Characterization
Authors: Brown Craig J. , Beaudoin Jonathan , Brissette Mike , Gazzola Vicki
Published: March 2019

The establishment of multibeam echosounders (MBES), as a mainstream tool in ocean mapping, has facilitated integrative approaches towards nautical charting, benthic habitat mapping, and seafloor geotechnical surveys. The combined acoustic response of the seabed and the subsurface can vary with MBES operating frequency. At worst, this can make for difficulties in merging the results from different mapping systems or mapping campaigns. However, at best, having observations of the same seafloor at different acoustic wavelengths allows for increased discriminatory power in seabed classification and characterization efforts. Here, we present the results from trials of a multispectral multibeam system (R2Sonic 2026 MBES, manufactured by R2Sonic, LLC, Austin, TX, USA) in the Bedford Basin, Nova Scotia. In this system, the frequency can be modified on a ping-by-ping basis, which can provide multi-spectral acoustic measurements with a single pass of the survey platform. The surveys were conducted at three operating frequencies (100, 200, and 400 kHz), and the resulting backscatter mosaics revealed differences in parts of the survey area between the frequencies. Ground validation surveys using a combination of underwater video transects and benthic grab and core sampling confirmed that these differences were due to coarse, dredge spoil material underlying a surface cover of mud. These innovations offer tremendous potential for application in the area of seafloor geological and benthic habitat mapping.
Explanatory Power of Pre-Issue Financial Strength for Long-Term Market Performance: Evidence from Initial Equity Offerings on an Emerging Market
Authors: Czapiewski Leszek , Lizińska Joanna
Published: March 2019

This study tests possible sources of long-term risk-adjusted returns on initial public offerings (IPO) in Poland under the calendar-time portfolio (CTP) approach. The moment of going public still remains a puzzle in many areas. Poland’s status as an emerging market has been indisputable for many years, though improvements in capital market infrastructure have led to its recent reclassification as a developed country. It is an important European equity market. Thus, research on IPO pricing explanation for Poland is important for both investors and academics. In this study, we estimate risk premiums and run regressions on four asset pricing models, including the latest innovation, which is the Fama-French 5-factor model. We also check the robustness. The research documents the existence of the long-run underperformance for Polish IPOs independently of the specification of the calendar-time portfolio approach as alphas range from −9.6% to −13.2% annually. We show that the underperformance is mainly driven by IPOs in a position of weak pre-issue financial health. More profitable IPOs experience less negative long-term returns and the underperformance is even absent in some specifications.
Potential Functions of the Gastrointestinal Microbiome Inhabiting the Length of the Rat Digest Tract
Authors: Li Dongyao , Chen Haiqin , Zhao Jianxin , Zhang Hao , Chen Wei
Published: March 2019

The rat is an important model animal used frequently in biological researches exploring the correlations between gut microbiome and a wide array of diseases. In this study, we used an extended ancestral-state reconstruction algorithm to predict the functional capabilities of the rat gastrointestinal microbiome. Our results indicate an apparent tendency toward metabolic heterogeneity along the longitudinal and transverse axes of the rat gastrointestinal tract (GIT). This heterogeneity was suggested by the enriched small-molecule transport activity and amino acid metabolism in the upper GIT, the aerobic energy metabolism in the stomach and the mucolysis-related metabolism in the lower GIT mucus layer. In contrast to prior results, many functional overlaps were observed when the gastrointestinal microbiomes of different hosts were compared. These overlaps implied that although both the biogeographic location and host genotype were prominent driving forces in shaping the gastrointestinal microbiota, the microbiome functions were similar across hosts when observed under similar physicochemical conditions at identical anatomical sites. Our work effectively complements the rat microbial biogeography dataset we released in 2017 and, thus, contributes to a better understanding and prediction of disease-related alterations in microbial community function.
The Impact of the C-Terminal Region on the Interaction of Topoisomerase II Alpha with Mitotic Chromatin
Authors: Antoniou-Kourounioti Melissa , Mimmack Michael L. , Porter Andrew C.G. , Farr Christine J.
Published: March 2019

Type II topoisomerase enzymes are essential for resolving DNA topology problems arising through various aspects of DNA metabolism. In vertebrates two isoforms are present, one of which (TOP2A) accumulates on chromatin during mitosis. Moreover, TOP2A targets the mitotic centromere during prophase, persisting there until anaphase onset. It is the catalytically-dispensable C-terminal domain of TOP2 that is crucial in determining this isoform-specific behaviour. In this study we show that, in addition to the recently identified chromatin tether domain, several other features of the alpha-C-Terminal Domain (CTD). influence the mitotic localisation of TOP2A. Lysine 1240 is a major SUMOylation target in cycling human cells and the efficiency of this modification appears to be influenced by T1244 and S1247 phosphorylation. Replacement of K1240 by arginine results in fewer cells displaying centromeric TOP2A accumulation during prometaphase-metaphase. The same phenotype is displayed by cells expressing TOP2A in which either of the mitotic phosphorylation sites S1213 or S1247 has been substituted by alanine. Conversely, constitutive modification of TOP2A by fusion to SUMO2 exerts the opposite effect. FRAP analysis of protein mobility indicates that post-translational modification of TOP2A can influence the enzyme’s residence time on mitotic chromatin, as well as its subcellular localisation.
Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats
Authors: Schiavone Stefania , Neri Margherita , Maffione Angela Bruna , Frisoni Paolo , Morgese Maria Grazia , Trabace Luigia , Turillazzi Emanuela
Published: March 2019

Several mechanisms underlying 3,4-Methylenedioxy-N-methylamphetamine (MDMA) neurotoxicity have been proposed, including neurochemical alterations and excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain are not fully known. We aimed to investigate possible alterations in the expression of the ROS producer NOX enzymes (NOX2, NOX1, and NOX4), NO generators (iNOS, eNOS, and nNOS), markers of oxidative (8-hydroxy-2′-deoxyguanosine, 8OHdG), and nitrosative (3-nitrotyrosine, NT) stress, as well as the colocalization between cells positive for the dopamine transporter (DT1) and cells expressing the neuronal nuclei (NeuN) marker, in the frontal cortex of rats receiving saline or MDMA, sacrificed 6 h, 16 h, or 24 h after its administration. MDMA did not affect NOX2, NOX1, and NOX4 immunoreactivity, whereas iNOS expression was enhanced. The number of NT-positive cells was increased in MDMA-exposed animals, whereas no differences were detected in 8OHdG expression among experimental groups. MDMA and NT markers colocalized with DT1 positive cells. DT1 immunostaining was found in NeuN-positive stained cells. Virtually no colocalization was observed with microglia and astrocytes. Moreover, MDMA immunostaining was not found in NOX2-positive cells. Our results suggest that iNOS-derived nitrosative stress, but not NOX enzymes, may have a crucial role in the pathogenesis of MDMA-induced neurotoxicity, highlighting the specificity of different enzymatic systems in the development of neuropathological alterations induced by the abuse of this psychoactive compound.
Efficient Editing of the Nuclear APT Reporter Gene in Chlamydomonas reinhardtii via Expression of a CRISPR-Cas9 Module
Authors: Guzmán-Zapata Daniel , Sandoval-Vargas José M. , Macedo-Osorio Karla S. , Salgado-Manjarrez Edgar , Castrejón-Flores José L. , Oliver-Salvador María del Carmen , Durán-Figueroa Noé V. , Nogué Fabien , Badillo-Corona Jesús A.
Published: March 2019

The clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9 (CRISPR/Cas9) technology is a versatile and useful tool to perform genome editing in different organisms ranging from bacteria and yeast to plants and mammalian cells. For a couple of years, it was believed that the system was inefficient and toxic in the alga Chlamydomonas reinhardtii. However, recently the system has been successfully implemented in this model organism, albeit relying mostly on the electroporation of ribonucleoproteins (RNPs) into cell wall deficient strains. This requires a constant source of RNPs and limits the application of the technology to strains that are not necessarily the most relevant from a biotechnological point of view. Here, we show that transient expression of the Streptococcus pyogenes Cas9 gene and sgRNAs, targeted to the single-copy nuclear apt9 gene, encoding an adenine phosphoribosyl transferase (APT), results in efficient disruption at the expected locus. Introduction of indels to the apt9 locus results in cell insensitivity to the otherwise toxic compound 2-fluoroadenine (2-FA). We have used agitation with glass beads and particle bombardment to introduce the plasmids carrying the coding sequences for Cas9 and the sgRNAs in a cell-walled strain of C. reinhardtii (CC-125). Using sgRNAs targeting exons 1 and 3 of apt9, we obtained disruption efficiencies of 3 and 30% on preselected 2-FA resistant colonies, respectively. Our results show that transient expression of Cas9 and a sgRNA can be used for editing of the nuclear genome inexpensively and at high efficiency. Targeting of the APT gene could potentially be used as a pre-selection marker for multiplexed editing or disruption of genes of interest.
The Impact of Tumor Heterogeneity on Diagnostics and Novel Therapeutic Strategies in Multiple Myeloma
Authors: Rasche Leo , Kortüm K. Martin , Raab Marc S. , Weinhold Niels
Published: March 2019

Myeloma is characterized by extensive inter-patient genomic heterogeneity due to multiple different initiating events. A recent multi-region sequencing study demonstrated spatial differences, with progression events, such as TP53 mutations, frequently being restricted to focal lesions. In this review article, we describe the clinical impact of these two types of tumor heterogeneity. Target mutations are often dominant at one site but absent at other sites, which poses a significant challenge to personalized therapy in myeloma. The same holds true for high-risk subclones, which can be locally restricted, and as such not detectable at the iliac crest, which is the usual sampling site. Imaging can improve current risk classifiers and monitoring of residual disease, but does not allow for deciphering the molecular characteristics of tumor clones. In the era of novel immunotherapies, the clinical impact of heterogeneity certainly needs to be re-defined. Yet, preliminary observations indicate an ongoing impact of spatial heterogeneity on the efficacy of monoclonal antibodies. In conclusion, we recommend combining molecular tests with imaging to improve risk prediction and monitoring of residual disease. Overcoming intra-tumor heterogeneity is the prerequisite for curing myeloma. Novel immunotherapies are promising but research addressing their impact on the spatial clonal architecture is highly warranted.
Bioavailability and In Vivo Antioxidant Activity of a Standardized Polyphenol Mixture Extracted from Brown Propolis
Authors: Curti Valeria , Zaccaria Vincenzo , Tsetegho Sokeng Arold Jorel , Dacrema Marco , Masiello Irene , Mascaro Anna , D’Antona Giuseppe , Daglia Maria
Published: March 2019

Several lines of evidence demonstrate the antioxidant, anti-inflammatory and antimicrobial activities of propolis, mostly ascribed to its polyphenol content. However, little is known regarding the bioavailability of propolis in acute and prolonged settings of oral administration. In this study, we first determined the content of the main polyphenols in a brown propolis extract obtained using a patented extraction method (Multi Dinamic Extraction—M.E.D.) by RP-HPLC-UV-PDA-MSn analysis, followed by the bioavailability of galangin and chrysin, the most abundant polyphenols in the mixture (7.8% and 7.5% respectively), following acute (single bolus of 500 mg/kg containing about 3.65 mg of the polyphenol mixture) and prolonged (100, 250 and 500 mg/kg body for 30 days) oral administration in 30 male 8 weeks old C57BL/6 wild-type mice. In the acute setting, blood was taken at 30 s and 5, 10, 15, 20, 25, 30, 45, 60 and 120 min following the oral bolus. In the prolonged setting, blood samples were obtained after 10, 20 or 30 days of administration. At the end of treatment, expression of antioxidant enzymes (superoxyde dismutase, SOD-1; catalase, CAT; glutathione peroxidase, GSS) was evaluated in liver tissue. Following both acute and prolonged administration, neither galangin nor chrysin were detectable in the plasma of mice, whereas the glucuronide metabolite of galangine was detectable 5 min after acute administration. At the end of the prolonged treatment SOD-1 was found to have increased significantly, unlike CAT and GSS. Overall, these data suggest that oral administration of whole brown propolis extract is followed by rapid absorption and metabolization of galangin followed by adaptations of the antioxidant first line defense system.
Extracellular Spermine Activates DNA Methyltransferase 3A and 3B
Authors: Fukui Taro , Soda Kuniyasu , Takao Koichi , Rikiyama Toshiki
Published: March 2019

We first demonstrated that long-term increased polyamine (spermine, spermidine, putrescine) intake elevated blood spermine levels in mice and humans, and lifelong consumption of polyamine-rich chow inhibited aging-associated increase in aberrant DNA methylation, inhibited aging-associated pathological changes, and extend lifespan of mouse. Because gene methylation status is closely associated with aging-associated conditions and polyamine metabolism is closely associated with regulation of gene methylation, we investigated the effects of extracellular spermine supplementation on substrate concentrations and enzyme activities involved in gene methylation. Jurkat cells and human mammary epithelial cells were cultured with spermine and/or D,L-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase. Spermine supplementation inhibited enzymatic activities of adenosylmethionine decarboxylase in both cells. The ratio of decarboxylated S-adenosylmethionine to S-adenosyl-L-methionine increased by DFMO and decreased by spermine. In Jurkat cells cultured with DFMO, the protein levels of DNA methyltransferases (DNMTs) 1, 3A and 3B were not changed, however the activity of the three enzymes markedly decreased. The protein levels of these enzymes were not changed by addition of spermine, DNMT 3A and especially 3B were activated. We show that changes in polyamine metabolism dramatically affect substrate concentrations and activities of enzymes involved in gene methylation.
Content-Aware Retargeted Image Quality Assessment
Authors: Zhang Tingting , Yu Ming , Guo Yingchun , Liu Yi
Published: March 2019

In targeting the low correlation between existing image scaling quality assessment methods and subjective awareness, a content-aware retargeted image quality assessment algorithm is proposed, which is based on the structural similarity index. In this paper, a similarity index, that is, a local structural similarity algorithm, which can measure different sizes of the same image is proposed. The Speed Up Robust Feature (SURF) algorithm is used to extract the local structural similarity and the image content loss degree. The significant area ratio is calculated by extracting the saliency region and the retargeted image quality assessment function is obtained by linear fusion. In the CUHK image database and the MIT RetargetMe database, compared with four representative assessment algorithms and other latest four kinds of retargeted image quality assessment algorithms, the experiment proves that the proposed algorithm has a higher correlation with Mean Opinion Score (MOS) values and corresponds with the result of human subjective assessment.
Halogen Bonding: A Halogen-Centered Noncovalent Interaction Yet to Be Understood
Authors: Varadwaj Pradeep R. , Varadwaj Arpita , Marques Helder M.
Published: March 2019

In addition to the underlying basic concepts and early recognition of halogen bonding, this paper reviews the conflicting views that consistently appear in the area of noncovalent interactions and the ability of covalently bonded halogen atoms in molecules to participate in noncovalent interactions that contribute to packing in the solid-state. It may be relatively straightforward to identify Type-II halogen bonding between atoms using the conceptual framework of σ-hole theory, especially when the interaction is linear and is formed between the axial positive region (σ-hole) on the halogen in one monomer and a negative site on a second interacting monomer. A σ-hole is an electron density deficient region on the halogen atom X opposite to the R–X covalent bond, where R is the remainder part of the molecule. However, it is not trivial to do so when secondary interactions are involved as the directionality of the interaction is significantly affected. We show, by providing some specific examples, that halogen bonds do not always follow the strict Type-II topology, and the occurrence of Type-I and -III halogen-centered contacts in crystals is very difficult to predict. In many instances, Type-I halogen-centered contacts appear simultaneously with Type-II halogen bonds. We employed the Independent Gradient Model, a recently proposed electron density approach for probing strong and weak interactions in molecular domains, to show that this is a very useful tool in unraveling the chemistry of halogen-assisted noncovalent interactions, especially in the weak bonding regime. Wherever possible, we have attempted to connect some of these results with those reported previously. Though useful for studying interactions of reasonable strength, IUPAC’s proposed “less than the sum of the van der Waals radii” criterion should not always be assumed as a necessary and sufficient feature to reveal weakly bound interactions, since in many crystals the attractive interaction happens to occur between the midpoint of a bond, or the junction region, and a positive or negative site.
Combinations of Symptoms in Emergency Presentations: Prevalence and Outcome
Authors: Kuster Tobias , Nickel Christian H. , Jenny Mirjam A. , Blaschke Lana L. , Bingisser Roland
Published: March 2019

The predictive power of certain symptoms, such as dyspnoea, is well known. However, research is limited to the investigation of single chief complaints. This is in contrast to patients in the emergency department (ED) presenting usually more than one symptom. We aimed to identify the most common combinations of symptoms and to report their related outcomes: hospitalisation, admission to intensive care units, and mortality. This is a secondary analysis of a consecutive sample of all patients presenting to the ED of the University Hospital Basel over a total time course of 6 weeks. The presence of 35 predefined symptoms was systematically assessed upon presentation. A total of 3960 emergency patients (median age 51, 51.7% male) were included. Over 130 combinations of two, 80 combinations of three, and 10 combinations of four symptoms occurred 42 times or more during a total inclusion period of 42 days. Two combinations of two symptoms were predictive for in-hospital mortality: weakness and fatigue (Odds ratio (OR) = 2.45), and weakness and headache (OR = 3.01). Combinations of symptoms were frequent. Nonspecific complaints (NSCs), such as weakness and fatigue, are among the most frequently reported combinations of symptoms, and are associated with adverse outcomes. Systematically assessing symptoms may add valuable information for prognosis and may therefore influence triage, clinical work-up, and disposition.
Progression-Related Loss of Stromal Caveolin 1 Levels Mediates Radiation Resistance in Prostate Carcinoma via the Apoptosis Inhibitor TRIAP1
Authors: Ketteler Julia , Panic Andrej , Reis Henning , Wittka Alina , Maier Patrick , Herskind Carsten , Yagüe Ernesto , Jendrossek Verena , Klein Diana
Published: March 2019

Tumour resistance to chemo- and radiotherapy, as well as molecularly targeted therapies, limits the effectiveness of current cancer treatments. We previously reported that the radiation response of human prostate tumours is critically regulated by CAV1 expression in stromal fibroblasts and that loss of stromal CAV1 expression in advanced tumour stages may contribute to tumour radiotherapy resistance. Here we investigated whether fibroblast secreted anti-apoptotic proteins could induce radiation resistance of prostate cancer cells in a CAV1-dependent manner and identified TRIAP1 (TP53 Regulated Inhibitor of Apoptosis 1) as a resistance-promoting CAV1-dependent factor. TRIAP1 expression and secretion was significantly higher in CAV1-deficient fibroblasts and secreted TRIAP1 was able to induce radiation resistance of PC3 and LNCaP prostate cancer cells in vitro, as well as of PC3 prostate xenografts derived from co-implantation of PC3 cells with TRIAP1-expressing fibroblasts in vivo. Immunohistochemical analyses of irradiated PC3 xenograft tumours, as well as of human prostate tissue specimen, confirmed that the characteristic alterations in stromal-epithelial CAV1 expression were accompanied by increased TRIAP1 levels after radiation in xenograft tumours and within advanced prostate cancer tissues, potentially mediating resistance to radiation treatment. In conclusion, we have determined the role of CAV1 alterations potentially induced by the CAV1-deficient, and more reactive, stroma in radio sensitivity of prostate carcinoma at a molecular level. We suggest that blocking TRIAP1 activity and thus avoiding drug resistance may offer a promising drug development strategy for inhibiting resistance-promoting CAV1-dependent signals.
Phytochemicals Targeting VEGF and VEGF-Related Multifactors as Anticancer Therapy
Authors: Parveen Amna , Subedi Lalita , Kim Heung Wan , Khan Zahra , Zahra Zahra , Farooqi Muhammad Qudratullah , Kim Sun Yeou
Published: March 2019

The role of vascular endothelial growth factor (VEGF) in cancer cells is not limited to angiogenesis; there are also multiple factors, such as neuropilins (non-tyrosine kinases receptors), tyrosine kinases receptors, immunodeficiencies, and integrins, that interact with VEGF signaling and cause cancer initiation. By combating these factors, tumor progression can be inhibited or limited. Natural products are sources of several bioactive phytochemicals that can interact with VEGF-promoting factors and inhibit them through various signaling pathways, thereby inhibiting cancer growth. This review provides a deeper understanding of the relation and interaction of VEGF with cancer-promoting factors and phytochemicals in order to develop multi-targeted cancer prevention and treatment.
Complex Microbiome in Brain Abscess Revealed by Whole-Genome Culture-Independent and Culture-Based Sequencing
Authors: Lin Jyun-Hong , Wu Zong-Yen , Gong Liang , Wong Chee-Hong , Chao Wen-Cheng , Yen Chun-Ming , Wang Ching-Ping , Wei Chia-Lin , Huang Yao-Ting , Liu Po-Yu
Published: March 2019

Brain abscess is a severe infectious disease with high mortality and mobility. Although culture-based techniques have been widely used for the investigation of microbial composition of brain abscess, these approaches are inherent biased. Recent studies using 16S ribosomal sequencing approaches revealed high complexity of the bacterial community involved in brain abscess but fail to detect fungal and viral composition. In the study, both culture-independent nanopore metagenomic sequencing and culture-based whole-genome sequencing using both the Illumina and the Nanopore platforms were conducted to investigate the microbial composition and genomic characterization in brain abscess. Culture-independent metagenomic sequencing revealed not only a larger taxonomic diversity of bacteria but also the presence of fungi and virus communities. The culture-based whole-genome sequencing identified a novel species in Prevotella and reconstructs a Streptococcus constellatus with a high GC-skew genome. Antibiotic-resistance genes CfxA and ErmF associated with resistance to penicillin and clindamycin were also identified in culture-based and culture-free sequencing. This study implies current understanding of brain abscess need to consider the broader diversity of microorganisms.
Prognostic Relevance of Altered Lymphocyte Subpopulations in Critical Illness and Sepsis
Authors: Hohlstein Philipp , Gussen Hendrik , Bartneck Matthias , Warzecha Klaudia Theresa , Roderburg Christoph , Buendgens Lukas , Trautwein Christian , Koch Alexander , Tacke Frank
Published: March 2019

Lymphopenia and functional defects in lymphocytes may impact the prognosis in patients with critical illness or sepsis. Therefore, we prospectively analyzed peripheral blood leukocytes from 63 healthy volunteers, 50 non-critically ill standard care (SC) patients with infections, and 105 intensive care unit (ICU) patients (52 with sepsis, 53 without sepsis) using flow cytometry. Compared to healthy volunteers, SC and ICU patients showed significant leukocytosis, especially in sepsis, while lymphocyte numbers were significantly decreased. All major lymphocyte populations (B, T, and natural killer (NK) cells) decreased in ICU patients. However, we observed a relative reduction of T cells, alongside decreased CD8+ T cells, in critically ill patients, independent of sepsis. High absolute T cell counts (>0.36/nL) at ICU admission were associated with a significantly reduced mortality, independent of patient’s age. Moreover, patients that survived ICU treatment showed dynamic changes within 48 h towards restoration of lymphopenia and T cell depletion, while non-surviving patients failed to restore lymphocyte counts. In conclusion, the flow-cytometric analysis of peripheral blood revealed striking changes in circulating lymphocyte subsets in critically ill patients, independent of sepsis. Lymphopenia and T cell depletion at ICU admission were associated with increased mortality, supporting their relevance as predictive biomarkers and potential therapeutic targets in intensive care medicine.
Identification of the Interface in a Binary Complex Plasma Using Machine Learning
Authors: Huang He , Schwabe Mierk , Du Cheng-Ran
Published: March 2019

A binary complex plasma consists of two different types of dust particles in an ionized gas. Due to the spinodal decomposition and force imbalance, particles of different masses and diameters are typically phase separated, resulting in an interface. Both external excitation and internal instability may cause the interface to move with time. Support vector machine (SVM) is a supervised machine learning method that can be very effective for multi-class classification. We applied an SVM classification method based on image brightness to locate the interface in a binary complex plasma. Taking the scaled mean and variance as features, three areas, namely small particles, big particles and plasma without dust particles, were distinguished, leading to the identification of the interface between small and big particles.
Chip Morphology and Delamination Characterization for Vibration-Assisted Drilling of Carbon Fiber-Reinforced Polymer
Authors: Hussein Ramy , Sadek Ahmad , Elbestawi Mohamed A. , Attia M. Helmi
Published: March 2019

Carbon fiber-reinforced polymers (CFRP) are widely used in the aerospace industry. A new generation of aircraft is being built using CFRP for up to 50% of their total weight, to achieve higher performance. Exit delamination and surface integrity are significant challenges reported during conventional drilling. Exit delamination influences the mechanical properties of machined parts and, consequently, reduces fatigue life. Vibration-assisted drilling (VAD) has much potential to overcome these challenges. This study is aimed at investigating exit delamination and geometrical accuracy during VAD at both low- and high-frequency ranges. The kinematics of VAD are used to investigate the relationship between the input parameters (cutting speed, feed, vibration frequency, and amplitude) and the uncut chip thickness. Exit delamination and geometrical accuracy are then evaluated in terms of mechanical and thermal load. The results show a 31% reduction in cutting temperature, as well as a significant enhancement in exit delamination, by using the VAD technology.
Gravity-Based Foundations in the Offshore Wind Sector
Authors: Esteban M. Dolores , López-Gutiérrez José-Santos , Negro Vicente
Published: March 2019

In recent years, the offshore wind industry has seen an important boost that is expected to continue in the coming years. In order for the offshore wind industry to achieve adequate development, it is essential to solve some existing uncertainties, some of which relate to foundations. These foundations are important for this type of project. As foundations represent approximately 35% of the total cost of an offshore wind project, it is essential that they receive special attention. There are different types of foundations that are used in the offshore wind industry. The most common types are steel monopiles, gravity-based structures (GBS), tripods, and jackets. However, there are some other types, such as suction caissons, tripiles, etc. For high water depths, the alternative to the previously mentioned foundations is the use of floating supports. Some offshore wind installations currently in operation have GBS-type foundations (also known as GBF: Gravity-based foundation). Although this typology has not been widely used until now, there is research that has highlighted its advantages over other types of foundation for both small and large water depth sites. There are no doubts over the importance of GBS. In fact, the offshore wind industry is trying to introduce improvements so as to turn GBF into a competitive foundation alternative, suitable for the widest ranges of water depth. The present article deals with GBS foundations. The article begins with the current state of the field, including not only the concepts of GBS constructed so far, but also other concepts that are in a less mature state of development. Furthermore, we also present a classification of this type of structure based on the GBS of offshore wind facilities that are currently in operation, as well as some reflections on future GBS alternatives.
Physical Modelling of Blue Mussel Dropper Lines for the Development of Surrogates and Hydrodynamic Coefficients
Authors: Landmann Jannis , Ongsiek Thorsten , Goseberg Nils , Heasman Kevin , Buck Bela H. , Paffenholz Jens-André , Hildebrandt Arndt
Published: March 2019

In this work, laboratory tests with live bivalves as well as the conceptual design of additively manufactured surrogate models are presented. The overall task of this work is to develop a surrogate best fitting to the live mussels tested in accordance to the identified surface descriptor, i.e., the Abbott–Firestone Curve, and to the hydrodynamic behaviour by means of drag and inertia coefficients. To date, very few investigations have focused on loads from currents as well as waves. Therefore, tests with a towing carriage were carried out in a wave flume. A custom-made rack using mounting clamps was built to facilitate carriage-run tests with minimal delays. Blue mussels (Mytilus edulis) extracted from a site in Germany, which were kept in aerated seawater to ensure their survival for the test duration, were used. A set of preliminary results showed drag and inertia coefficients C D and C M ranging from 1.16–3.03 and 0.25 to 1.25. To derive geometrical models of the mussel dropper lines, 3-D point clouds were prepared by means of 3-D laser scanning to obtain a realistic surface model. Centered on the 3-D point cloud, a suitable descriptor for the mass distribution over the surface was identified and three 3-D printed surrogates of the blue mussel were developed for further testing. These were evaluated regarding their fit to the original 3-D point cloud of the live blue mussels via the chosen surface descriptor.
Determining Distribution for the Quotients of Dependent and Independent Random Variables by Using Copulas
Authors: Ly Sel , Pho Kim-Hung , Ly Sal , Wong Wing-Keung
Published: March 2019

Determining distributions of the functions of random variables is a very important problem with a wide range of applications in Risk Management, Finance, Economics, Science, and many other areas. This paper develops the theory on both density and distribution functions for the quotient Y = X 1 X 2 and the ratio of one variable over the sum of two variables Z = X 1 X 1 + X 2 of two dependent or independent random variables X 1 and X 2 by using copulas to capture the structures between X 1 and X 2 . Thereafter, we extend the theory by establishing the density and distribution functions for the quotients Y = X 1 X 2 and Z = X 1 X 1 + X 2 of two dependent normal random variables X 1 and X 2 in the case of Gaussian copulas. We then develop the theory on the median for the ratios of both Y and Z on two normal random variables X 1 and X 2 . Furthermore, we extend the result of median for Z to a larger family of symmetric distributions and symmetric copulas of X 1 and X 2 . Our results are the foundation of any further study that relies on the density and cumulative probability functions of ratios for two dependent or independent random variables. Since the densities and distributions of the ratios of both Y and Z are in terms of integrals and are very complicated, their exact forms cannot be obtained. To circumvent the difficulty, this paper introduces the Monte Carlo algorithm, numerical analysis, and graphical approach to efficiently compute the complicated integrals and study the behaviors of density and distribution. We illustrate our proposed approaches by using a simulation study with ratios of normal random variables on several different copulas, including Gaussian, Student-t, Clayton, Gumbel, Frank, and Joe Copulas. We find that copulas make big impacts from different Copulas on behavior of distributions, especially on median, spread, scale and skewness effects. In addition, we also discuss the behaviors via all copulas above with the same Kendall’s coefficient. The approaches developed in this paper are flexible and have a wide range of applications for both symmetric and non-symmetric distributions and also for both skewed and non-skewed copulas with absolutely continuous random variables that could contain a negative range, for instance, generalized skewed-t distribution and skewed-t Copulas. Thus, our findings are useful for academics, practitioners, and policy makers.
Local Perspectives on Ecosystem Service Trade-Offs in a Forest Frontier Landscape in Myanmar
Authors: Feurer Melanie , Heinimann Andreas , Schneider Flurina , Jurt Christine , Myint Win , Zaehringer Julie Gwendolin
Published: March 2019

Extensive land use changes in forest frontier landscapes are leading to trade-offs in the supply of ecosystem services (ES) with, in many cases, as yet unknown effects on human well-being. In the Tanintharyi Region of Myanmar, a forest frontier landscape facing oil palm and rubber expansion, little is known about local perspectives on ES and the direct impact of trade-offs from land use change. This study assessed the trade-offs experienced with respect to 10 locally important ES from land user perspectives using social valuation techniques. The results show that while intact forests provide the most highly valued ES bundle, the conversion to rubber plantations entails fewer negative trade-offs than that to oil palm. Rubber plantations offer income, fuelwood, a good microclimate, and even new cultural identities. By contrast, oil palm concessions have caused environmental pollution, and, most decisively, have restricted local people’s access to the respective lands. The ES water flow regulation is seen as the most critical if more forest is converted; other ES, such as non-timber forest products, can be more easily substituted. We conclude that, from local perspectives, the impact of ES trade-offs highly depends on access to land and opportunities to adapt to change.
Absorption Wavebands for Discriminating Oxidation Time of Engine Oil as Detected by FT-IR Spectroscopy
Authors: Abdul-Munaim Ali Mazin , Holland Torrey , Sivakumar Poopalasingam , Watson Dennis G.
Published: March 2019

Fourier Transform-Infrared (FT-IR) spectroscopy was used to analyze gasoline engine oil (SAE 5W20) samples that were exposed to seven different oxidation times (0 h, 24 h, 48 h, 72 h, 96 h, 120 h, and 144 h) to determine the best wavenumbers and wavenumber ranges for the discrimination of the oxidation times. The thermal oxidation process generated oil samples with varying total base number (TBN) levels. Each wavenumber (400–3900 cm−1) and wavenumber ranges identified from the literature and this study were statistically analyzed to determine which wavenumbers and wavenumber ranges could discriminate among all oxidation times. Linear regression was used with the best wavenumbers and wavenumber ranges to predict oxidation time.
Convergence Theorems for Common Solutions of Split Variational Inclusion and Systems of Equilibrium Problems
Authors: Tang Yan , Cho Yeol Je
Published: March 2019

In this paper, the split variational inclusion problem (SVIP) and the system of equilibrium problems (EP) are considered in Hilbert spaces. Inspired by the works of Byrne et al., López et al., Moudafi and Thukur, Sobumt and Plubtieng, Sitthithakerngkiet et al. and Eslamian and Fakhri, a new self-adaptive step size algorithm is proposed to find a common element of the solution set of the problems SVIP and EP. Convergence theorems are established under suitable conditions for the algorithm and application to the common solution of the fixed point problem, and the split convex optimization problem is considered. Finally, the performances and computational experiments are presented and a comparison with the related algorithms is provided to illustrate the efficiency and applicability of our new algorithms.
The Generalized Quadratic Gauss Sum and Its Fourth Power Mean
Authors: Shen Shimeng , Zhang Wenpeng
Published: March 2019

In this article, our main purpose is to introduce a new and generalized quadratic Gauss sum. By using analytic methods, the properties of classical Gauss sums, and character sums, we consider the calculating problem of its fourth power mean and give two interesting computational formulae for it.
Antiproliferative Activity of (-)-Rabdosiin Isolated from Ocimum sanctum L.
Authors: Flegkas Alexandros , Milosević Ifantis Tanja , Barda Christina , Samara Pinelopi , Tsitsilonis Ourania , Skaltsa Helen
Published: March 2019

Background: Ocimum sanctum L. (holy basil; Tulsi in Hindi) is an important medicinal plant, traditionally used in India. Methods: The phytochemical study of the nonpolar (dichloromethane 100%) and polar (methanol:water; 7:3) extracts yielded fourteen compounds. Compounds 6, 7, 9, 11, 12, and 13, along with the methanol:water extract were evaluated for their cytotoxicity against the human cancer cell lines MCF-7, SKBR3, and HCT-116, and normal peripheral blood mononuclear cells (PBMCs). Results: Five terpenoids, namely, ursolic acid (1), oleanolic acid (2), betulinic acid (3), stigmasterol (4), and β-caryophyllene oxide (5); two lignans, i.e., (-)-rabdosiin (6) and shimobashiric acid C (7); three flavonoids, luteolin (8), its 7-O-β-D-glucuronide (9), apigenin 7-O-β-D-glucuronide (10); and four phenolics, (E)-p-coumaroyl 4-O-β-D-glucoside (11), 3-(3,4-dihydroxyphenyl) lactic acid (12), protocatechuic acid (13), and vanillic acid (14) were isolated. Compound 6 was the most cytotoxic against the human cancer lines assessed and showed very low cytotoxicity against PBMCs. Conclusions: Based on these results, the structure of compound 6 shows some promise as a selective anticancer drug scaffold.
Mechanical Properties of a Thermally-aged Cast Duplex Stainless Steel by in Situ Tensile Test at the Service Temperature
Authors: Zhang Qingdong , Ma Sida , Jing Tao
Published: March 2019

Z3CN20.09M cast duplex stainless steel (CDSS) has been used for primary coolant water pipes in pressurized water reactors due to its excellent mechanical properties. Such pipes operate at an elevated service temperature (~320 °C) and experience issues of thermal aging embrittlement. In situ tensile tests were conducted to investigate the deformation mechanisms of Z3CN20.09M CDSS after long-term thermal aging at 475 °C for up to 2000 h in both optical microscope and scanning electron microscope at 320 °C. For the 320 °C tests, the tensile stress and other mechanical properties, e.g. the yield stress and the ultimate tensile strength, increase during the thermal aging process and recover to almost the same level as the unaged condition after annealing heat-treatment, which is caused by the formation and dissolution of precipitation during aging and anneal heat-treatment, respectively. For the slip mechanism, straight slip lines form first in the austenite phase. When these slip lines reach the austenite/ferrite interface, three kinds of slip systems are found in the ferrite phase. During the fracture process, the austenite phase is torn apart and the ferrite phase shows a significant elongation. The role of the ferrite phase is to hold the austenite matrix, thus increasing the tensile strength of this steel.