bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic Waste Buyback as a Viable Method to Enhance Sustainable Municipal Solid Waste Management in Developing Countries
Authors: Hettiarachchi Hiroshan , Meegoda Jay N. , Ryu Sohyeon
Published: November 2018

Many developing countries have inadequate Municipal Solid Waste (MSW) management systems due to lack of not only the awareness, technologies, finances, but also a proper governance that is able to enforce and monitor the regulations. Not all the solutions practiced by and in developed countries fit to the developing country contexts. The local conditions and limitations must always be taken into account when proposing waste management options for developing countries. The excessively high organic waste fraction in MSW and relatively inexpensive labor markets available in developing countries are two of the strengths that have not yet been utilized fully. This manuscript is an attempt to point out the benefits we receive from the above two strengths if we establish organic waste buyback programs. This can only become successful if we find solutions to: (1) collect source-separated organic waste, and then (2) find stable markets for the products made from organic waste. Compost or biogas could be the best bet developing countries can consider as products. However, there must be some policy interventions to support buyback programs at the waste collection stage as well as at the product marketing stage. Implementation of such organic waste buyback centers that can offer some incentives can indirectly motivate residents to do source separation. This will in turn also help promote more recycling, as any waste bin that has no organics in it is much easier for anyone (e.g., waste pickers) to look for other recyclables. Developing country settings such as the Green Container composting program in Cajicá, Colombia, and buyback centers in South Africa that are presented later in the manuscript are thought to be the places where the concept can be implemented with little effort. The environment, economy, and society are considered to be the three dimensions (or pillars) of sustainability. Interestingly, the organic waste buyback centers solution has positive implications on all three aspects of sustainability. Thus, it also supports the 2030 Agenda of the United Nations (UN), by making specific contributions to the Sustainable Development Goals (SDGs) such as zero hunger (SDG 2), affordable and clean energy (SDG 7), climate action (SDG 13), clean water and sanitation (SDG 6), and sustainable cities and communities (SDG 11).
Carcinogenic Potency of Airborne Polycyclic Aromatic Hydrocarbons in Relation to the Particle Fraction Size
Authors: Pehnec Gordana , Jakovljević Ivana
Published: November 2018

Polycyclic aromatic hydrocarbons (PAHs) that are bound to particulate matter can have adverse effects on human health. Particle size plays an important role in assessing health risks. The aim of this study was to compare concentrations of PAHs bound to particle fractions PM10, PM2.5, and PM1, as well as to estimate their carcinogenic potency and relative contributions of the individual PAHs to the carcinogenic potency in relation to the size of the particle. Measurements of ten PAHs were carried out in 2014 at an urban location in the northern part of Zagreb, Croatia. 24-h samples of the PM10, PM2.5, and PM1 particle fraction were collected over forty days per season. Carcinogenic potency of PAHs was estimated by calculating benzo(a)pyrene equivalent concentrations while using three different toxic equivalence factor (TEF) schemes. The total carcinogenic potency (TCP) and percentage contributions differed significantly depending on the TEF scheme used. The lowest PAH mass concentrations and TCPs were in summer and the highest in winter. The contributions of individual PAHs to the sum of PAH mass concentrations remained similar in all fractions and seasons, while in fractions PM10–2.5 and PM2.5–1 they varied significantly. Road traffic represented the important source of PAHs in all fractions and throughout all seasons. Other sources (wood and biomass burning, petroleum combustion) were also present, especially during winter as a consequence of household heating. The highest contribution to the TCP came from benzo(a)pyrene, dibenzo(ah)antrachene, indeno(1,2,3,cd)pyrene, and benzo(b)fluoranthene (together between 87% and 96%) in all fractions and seasons. In all cases, BaP showed the highest contribution to the TCP regardless relatively low contributions to the mass of total PAHs and it can be considered as a good representative for assessing the carcinogenicity of the PAH mixture. When comparing the TCP of PAHs in PM10 and PM2.5 fractions, it was found that about 21–26% of carcinogenic potency of the PAH mixture belonged to the PM2.5 fraction. Comparison of TCP in PM2.5 and PM1 showed that about 86% of carcinogenic potency belonged to the PM1 fraction, regardless of the TEF scheme used.
Winter Is Coming: A Socio-Environmental Monitoring and Spatiotemporal Modelling Approach for Better Understanding a Respiratory Disease
Authors: Marek Lukas , Campbell Malcolm , Epton Michael , Kingham Simon , Storer Malina
Published: November 2018

Chronic Obstructive Pulmonary Disease is a progressive lung disease affecting the respiratory function of every sixth New Zealander and over 300 million people worldwide. In this paper, we explored how the combination of social, demographical and environmental conditions (represented by increased winter air pollution) affected hospital admissions due to COPD in an urban area of Christchurch (NZ). We juxtaposed the hospitalisation data with dynamic air pollution data and census data to investigate the spatiotemporal patterns of hospital admissions. Spatial analysis identified high-risk health hot spots both overall and season specific, exhibiting higher rates in winter months not solely due to air pollution, but rather as a result of its combination with other factors that initiate deterioration of breathing, increasing impairments and lead to the hospitalisation of COPD patients. From this we found that socioeconomic deprivation and air pollution, followed by the age and ethnicity structure contribute the most to the increased winter hospital admissions. This research shows the continued importance of including both individual (composition) and area level (composition) factors when examining and analysing disease patterns.
Impaired Water Hazard Zones: Mapping Intersecting Environmental Health Vulnerabilities and Polluter Disproportionality
Authors: Liévanos Raoul S.
Published: November 2018

This study advanced a rigorous spatial analysis of surface water-related environmental health vulnerabilities in the California Bay-Delta region, USA, from 2000 to 2006. It constructed a novel hazard indicator—“impaired water hazard zones’’—from regulatory estimates of extensive non-point-source (NPS) and point-source surface water pollution, per section 303(d) of the U.S. Clean Water Act. Bivariate and global logistic regression (GLR) analyses examined how established predictors of surface water health-hazard exposure vulnerability explain census block groups’ proximity to impaired water hazard zones in the Bay-Delta. GLR results indicate the spatial concentration of Black disadvantage, isolated Latinx disadvantage, low median housing values, proximate industrial water pollution levels, and proximity to the Chevron oil refinery—a disproportionate, “super emitter”, in the Bay-Delta—significantly predicted block group proximity to impaired water hazard zones. A geographically weighted logistic regression (GWLR) specification improved model fit and uncovered spatial heterogeneity in the predictors of block group proximity to impaired water hazard zones. The modal GWLR results in Oakland, California, show how major polluters beyond the Chevron refinery impair the local environment, and how isolated Latinx disadvantage was the lone positively significant population vulnerability factor. The article concludes with a discussion of its scholarly and practical implications.
Disordered Regions of Mixed Lineage Leukemia 4 (MLL4) Protein Are Capable of RNA Binding
Authors: Szabó Beáta , Murvai Nikoletta , Abukhairan Rawan , Schád Éva , Kardos József , Szeder Bálint , Buday László , Tantos Ágnes
Published: November 2018

Long non-coding RNAs (lncRNAs) are emerging as important regulators of cellular processes and are extensively involved in the development of different cancers; including leukemias. As one of the accepted methods of lncRNA function is affecting chromatin structure; lncRNA binding has been shown for different chromatin modifiers. Histone lysine methyltransferases (HKMTs) are also subject of lncRNA regulation as demonstrated for example in the case of Polycomb Repressive Complex 2 (PRC2). Mixed Lineage Leukemia (MLL) proteins that catalyze the methylation of H3K4 have been implicated in several different cancers; yet many details of their regulation and targeting remain elusive. In this work we explored the RNA binding capability of two; so far uncharacterized regions of MLL4; with the aim of shedding light to the existence of possible regulatory lncRNA interactions of the protein. We demonstrated that both regions; one that contains a predicted RNA binding sequence and one that does not; are capable of binding to different RNA constructs in vitro. To our knowledge, these findings are the first to indicate that an MLL protein itself is capable of lncRNA binding.
The Mitochondrial Genes BAK1, FIS1 and SFN are Linked with Alterations in Mitochondrial Membrane Potential in Barrett’s Esophagus
Authors: Phelan James J. , MacCarthy Finbar , O’Toole Dermot , Ravi Narayanasamy , Reynolds John V. , O’Sullivan Jacintha
Published: November 2018

Barrett’s esophagus and esophageal cancer lack prognostic markers that allow the tailoring of personalized medicine and biomarkers with potential to provide insight into treatment response. This study aims to characterize mitochondrial function across the metaplasia-dysplasia-adenocarcinoma disease sequence in Barrett’s esophagus and examines the functional effect of manipulating mitochondrial genes. Mitochondrial genes of interest were validated in in vitro cell lines across the metaplasia (QH), dysplasia (GO) and adenocarcinoma (OE33) sequence and in in vivo patient tissue samples. These genes were subsequently knocked down in QH and OE33 cells and the functional effect of siRNA-induced knockdown on reactive oxygen species production, mitochondrial mass, mitochondrial membrane potential and cellular metabolism was investigated. Three global mitochondrial genes (BAK1, FIS1 and SFN) were differentially altered across the in vivo Barrett’s disease sequence. We also demonstrate that knockdown of BAK1, FIS1 and SFN in vitro resulted in significant alterations in mitochondrial membrane potential; however, no differences in reactive oxygen species or mitochondrial mass were observed. Furthermore, knockdown of these genes in esophageal adenocarcinoma cells significantly altered cellular metabolism. In conclusion, we found that differential expression of BAK1, FIS1, and SFN were altered across the Barrett’s disease sequence and manipulation of these genes elicited significant effects on mitochondrial membrane potential.
A Novel High Sensitivity Type II Collagen Blood-Based Biomarker, PRO-C2, for Assessment of Cartilage Formation
Authors: Luo Yunyun , He Yi , Reker Ditte , Gudmann Natasja Stæhr , Henriksen Kim , Simonsen Ole , Ladel Christoph , Michaelis Martin , Mobasheri Ali , Karsdal Morten , Bay-Jensen Anne-Christine
Published: November 2018

N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH2-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utility of PIIBNP as a marker in preclinical and clinical settings has not been fully investigated yet. In this study, we aimed to characterize an antibody targeting human PIIBNP and to develop an immunoassay assessing type II collagen synthesis in human blood samples. A high sensitivity electrochemiluminescence immunoassay, hsPRO-C2, was developed using a well-characterized antibody against human PIIBNP. Human cartilage explants from replaced osteoarthritis knees were cultured for ten weeks in the presence of growth factors, insulin-like growth factor 1 (IGF-1) or recombinant human fibroblast growth factor 18 (rhFGF-18). The culture medium was changed every seven days, and levels of PIIBNP, PIIANP, and matrix metalloproteinase 9-mediated degradation of type II collagen (C2M) were analyzed herein. Serum samples from a cross-sectional knee osteoarthritis cohort, as well as pediatric and rheumatoid arthritis samples, were assayed for PIIBNP and PIIANP. Western blot showed that the antibody recognized PIIBNP either as a free fragment or attached to the main molecule. Immunohistochemistry demonstrated that PIIBNP was predominately located in the extracellular matrix of the superficial and deep zones and chondrocytes in both normal and osteoarthritic articular cartilage. In addition, the hsPRO-C2 immunoassay exhibits acceptable technical performances. In the human cartilage explants model, levels of PIIBNP, but not PIIANP and C2M, were increased (2 to 7-fold) time-dependently in response to IGF-1. Moreover, there was no significant correlation between PIIBNP and PIIANP levels when measured in knee osteoarthritis, rheumatoid arthritis, and pediatric serum samples. Serum PIIBNP was significantly higher in controls (KL0/1) compared to OA groups (KL2/3/4, p = 0.012). The hsPRO-C2 assay shows completely different biological and clinical patterns than PIIANP ELISA, suggesting that it may be a promising biomarker of cartilage formation.
Label-Free Monitoring of Uptake and Toxicity of Endoprosthetic Wear Particles in Human Cell Cultures
Authors: Jonitz-Heincke Anika , Tillmann Jenny , Ostermann Melanie , Springer Armin , Bader Rainer , Høl Paul , Cimpan Mihaela
Published: November 2018

The evaluation of the biological effects of endoprosthetic wear particles on cells in vitro relies on a variety of test assays. However, most of these methods are susceptible to particle-induced interferences; therefore, label-free testing approaches emerge as more reliable alternatives. In this study, impedance-based real-time monitoring of cellular viability and metabolic activity were performed following exposure to metallic and ceramic wear particles. Moreover, label-free imaging of particle-exposed cells was done by high-resolution darkfield microscopy (HR-ODM) and field emission scanning electron microscopy (FESEM). The isolated human fibroblasts were exposed to CoCr28Mo6 and alumina matrix composite (AMC) ceramic particles. HR-ODM and FESEM revealed ingested particles. For impedance measurements, cells were seeded on gold-plated microelectrodes. Cellular behavior was monitored over a period of 48 h. CoCr28Mo6 and AMC particle exposure affected cell viability in a concentration-dependent manner, i.e., 0.01 mg/mL particle solutions led to small changes in cell viability, while 0.05 mg/mL resulted in a significant reduction of viability. The effects were more pronounced after exposure to CoCr28Mo6 particles. The results were in line with light and darkfield microcopy observations indicating that the chosen methods are valuable tools to assess cytotoxicity and cellular behavior following exposure to endoprosthetic wear particles.
Expression of the Biofilm-Associated Genes in Methicillin-Resistant Staphylococcus aureus in Biofilm and Planktonic Conditions
Authors: Kot Barbara , Sytykiewicz Hubert , Sprawka Iwona
Published: November 2018

The role of genes that are essential for development of Staphylococcus aureus biofilm during infection is not fully known. mRNA from two methicillin-resistant S. aureus strains that formed weak and strong biofilm on polystyrene plates were isolated at five time points from cells grown in biofilm and planktonic culture. Quantitative real-time PCR analysis showed that the expression levels of investigated genes under biofilm conditions were significantly higher than under planktonic conditions. The expression levels of the gene encoding elastin binding protein (ebps) and laminin binding protein (eno) were significantly increased in biofilm at 3 h, both in strongly and weakly adhering strain. The peak expression of fib gene encoding fibrinogen binding protein was found at 6 and 8 h in the case of strongly and weakly adhering strain, respectively. The expression of icaA and icaD genes in both strains was significantly higher under biofilm conditions when comparing to planktonic cells during 12 h. The expression level of the genes encoding binding proteins and the glucosamine polymer polysaccharide intercellular adhesin (PIA) slowly decreased after 24 h. Finally, we found that the expression levels of genes encoding binding factors in weakly adhering strain were significantly lower than in strongly adhering strain.
Minimal/Measurable Residual Disease Monitoring in NPM1-Mutated Acute Myeloid Leukemia: A Clinical Viewpoint and Perspectives
Authors: Forghieri Fabio , Comoli Patrizia , Marasca Roberto , Potenza Leonardo , Luppi Mario
Published: November 2018

Acute myeloid leukemia (AML) with NPM1 gene mutations is currently recognized as a distinct entity, due to its unique biological and clinical features. We summarize here the results of published studies investigating the clinical application of minimal/measurable residual disease (MRD) in patients with NPM1-mutated AML, receiving either intensive chemotherapy or hematopoietic stem cell transplantation. Several clinical trials have so far demonstrated a significant independent prognostic impact of molecular MRD monitoring in NPM1-mutated AML and, accordingly, the Consensus Document from the European Leukemia Net MRD Working Party has recently recommended that NPM1-mutated AML patients have MRD assessment at informative clinical timepoints during treatment and follow-up. However, several controversies remain, mainly with regard to the most clinically significant timepoints and the MRD thresholds to be considered, but also with respect to the optimal source to be analyzed, namely bone marrow or peripheral blood samples, and the correlation of MRD with other known prognostic indicators. Moreover, we discuss potential advantages, as well as drawbacks, of newer molecular technologies such as digital droplet PCR and next-generation sequencing in comparison to conventional RQ-PCR to quantify NPM1-mutated MRD. In conclusion, further prospective clinical trials are warranted to standardize MRD monitoring strategies and to optimize MRD-guided therapeutic interventions in NPM1-mutated AML patients.
AMP-Activated Protein Kinase and Host Defense against Infection
Authors: Silwal Prashanta , Kim Jin Kyung , Yuk Jae-Min , Jo Eun-Kyeong
Published: November 2018

5′-AMP-activated protein kinase (AMPK) plays diverse roles in various physiological and pathological conditions. AMPK is involved in energy metabolism, which is perturbed by infectious stimuli. Indeed, various pathogens modulate AMPK activity, which affects host defenses against infection. In some viral infections, including hepatitis B and C viral infections, AMPK activation is beneficial, but in others such as dengue virus, Ebola virus, and human cytomegaloviral infections, AMPK plays a detrimental role. AMPK-targeting agents or small molecules enhance the antiviral response and contribute to the control of microbial and parasitic infections. In addition, this review focuses on the double-edged role of AMPK in innate and adaptive immune responses to infection. Understanding how AMPK regulates host defenses will enable development of more effective host-directed therapeutic strategies against infectious diseases.
Modeling of Protein Structural Flexibility and Large-Scale Dynamics: Coarse-Grained Simulations and Elastic Network Models
Authors: Kmiecik Sebastian , Kouza Maksim , Badaczewska-Dawid Aleksandra E. , Kloczkowski Andrzej , Kolinski Andrzej
Published: November 2018

Fluctuations of protein three-dimensional structures and large-scale conformational transitions are crucial for the biological function of proteins and their complexes. Experimental studies of such phenomena remain very challenging and therefore molecular modeling can be a good alternative or a valuable supporting tool for the investigation of large molecular systems and long-time events. In this minireview, we present two alternative approaches to the coarse-grained (CG) modeling of dynamic properties of protein systems. We discuss two CG representations of polypeptide chains used for Monte Carlo dynamics simulations of protein local dynamics and conformational transitions, and highly simplified structure-based elastic network models of protein flexibility. In contrast to classical all-atom molecular dynamics, the modeling strategies discussed here allow the quite accurate modeling of much larger systems and longer-time dynamic phenomena. We briefly describe the main features of these models and outline some of their applications, including modeling of near-native structure fluctuations, sampling of large regions of the protein conformational space, or possible support for the structure prediction of large proteins and their complexes.
Possible Involvement of 2′,3′-Cyclic Nucleotide-3′-Phosphodiesterase in the Protein Phosphorylation-Mediated Regulation of the Permeability Transition Pore
Authors: Baburina Yulia , Odinokova Irina , Azarashvili Tamara , Akatov Vladimir , Sotnikova Linda , Krestinina Olga
Published: November 2018

Calcium as a secondary messenger regulates the phosphorylation of several membrane-bound proteins in brain and liver mitochondria. Regulation of the activity of different protein kinases and phosphatases by Ca2+ occurs through its binding with calmodulin. The protein phosphorylation is strongly dependent on the Ca2+-induced mitochondrial permeability transition pore (mPTP) opening. 2′,3′-Cyclic nucleotide-3′-phosphodiesterase (CNPase) was phosphorylated by protein kinases A and C. CNPase and melatonin (MEL) might interact with calmodulin. The effects of the calmodulin antagonist calmidazolium and the inhibitor of protein kinase A H89 on mPTP opening in rat brain mitochondria of male Wistar rats were investigated. In addition, the role of CNPase, serine/threonine kinases, and MEL in the mPTP opening was examined. The anti-CNPase antibody added to rat brain mitochondria (RBM) reduced the content of CNPase in mitochondria. The threshold [Ca2+] decreased, and mitochondrial swelling was accelerated in the presence of the anti-CNPase antibody. H89 enhanced the effect of anti-CNPase antibody and accelerated the swelling of mitochondria, while CmZ abolished the effect of anti-CNPase antibody under mPTP opening. The levels of phospho-Akt and phospho-GSK3β increased, while the MEL content did not change. It can be assumed that CNPase may be involved in the regulation of these kinases, which in turn plays an important role in mPTP functioning.
DNA Modified with Boron–Metal Cluster Complexes [M(C2B9H11)2]—Synthesis, Properties, and Applications
Authors: Olejniczak Agnieszka B. , Nawrot Barbara , Leśnikowski Zbigniew J.
Published: November 2018

Together with tremendous progress in biotechnology, nucleic acids, while retaining their status as “molecules of life”, are becoming “molecular wires”, materials for the construction of molecular structures at the junction between the biological and abiotic worlds. Herein, we present an overview of the approaches for incorporating metal centers into nucleic acids based on metal–boron cluster complexes (metallacarboranes) as the metal carriers. The methods are modular and versatile, allowing practical access to innovative metal-containing DNA for various applications, such as nucleic acid therapeutics, electrochemical biosensors, infrared-sensitive probes, and building blocks for nanoconstruction.
NRF2 Is One of the Players Involved in Bone Marrow Mediated Drug Resistance in Multiple Myeloma
Authors: Yen Chia-Hung , Hsiao Hui-Hua
Published: November 2018

Multiple myeloma with clonal plasma expansion in bone marrow is the second most common hematologic malignancy in the world. Though the improvement of outcomes from the achievement of novel agents in recent decades, the disease progresses and leads to death eventually due to the elusive nature of myeloma cells and resistance mechanisms to therapeutic agents. In addition to the molecular and genetic basis of resistance pathomechanisms, the bone marrow microenvironment also contributes to disease progression and confers drug resistance in myeloma cells. In this review, we focus on the current state of the literature in terms of critical bone marrow microenvironment components, including soluble factors, cell adhesion mechanisms, and other cellular components. Transcriptional factor nuclear factor erythroid-derived-2-like 2 (NRF2), a central regulator for anti-oxidative stresses and detoxification, is implicated in chemoresistance in several cancers. The functional roles of NRF2 in myeloid-derived suppressor cells and multiple myeloma cells, and the potential of targeting NRF2 for overcoming microenvironment-mediated drug resistance in multiple myeloma are also discussed.
Pediococcus pentosaceus-Fermented Cordyceps militaris Inhibits Inflammatory Reactions and Alleviates Contact Dermatitis
Authors: Kwon Ha-Kyoung , Song Min-Jung , Lee Hye-Ji , Park Tae-Sik , Kim Moon Il , Park Hye-Jin
Published: November 2018

Cordyceps militaris is a medicinal mushroom used to treat immune-related diseases in East Asia. We investigated the anti-inflammatory effect of the extract of C. militaris grown on germinated Rhynchosia nulubilis (GRC) fermented with Pediococcus pentosaceus ON89A isolated from onion (GRC-ON89A) in vivo as well as in vitro. The anti-inflammatory effect of GRC-ON89A was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The total polyphenol content (TPC) and total flavonoid content (TFC) in the GRC-ON89A ethanol extract were significantly increased compared to that in GRC. GRC-ON89A hexane fraction (GRC-ON89A-Hex) inhibited the release of nitric oxide (NO) compared to that of the LPS-treated control without cytotoxicity in LPS-stimulated RAW 264.7 macrophages. GRC-ON89A-Hex decreased the inducible NO synthase (iNOS), cyclooxygenase 2 (COX2), and tumor necrosis factor (TNF)-α mRNA expression in LPS-stimulated RAW 264.7 macrophages. In addition, pre-treatment with GRC-ON89A-Hex significantly inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. To induce allergic contact dermatitis (ACD), 1-fluoro-2, 4-dinitrofluorobenzene (DNFB) was applied to the surface of the right ears of C57BL/6N mice. GRC-ON89A reduced the ear swelling and thickness in DNFB-induced ACD mice. This study demonstrates the potential usefulness of GRC-ON89A as an anti-inflammatory dietary supplement or drug.
Emerging Role of Immune Checkpoint Blockade in Pancreatic Cancer
Authors: Macherla Shravanti , Laks Shachar , Naqash Abdul Rafeh , Bulumulle Anushi , Zervos Emmanuel , Muzaffar Mahvish
Published: November 2018

Immune checkpoint blockade (ICB) with programmed cell death protein-1(PD-1)/programmed death ligand -1(PD-L1) antibodies has revolutionized the management of several cancers, especially non-small cell lung cancer, melanoma, urothelial, and renal cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers associated with high morbidity and mortality. Based on available data, it’s obvious that ICB has limited success in PDACs, which can be explained by the low immunogenicity and immunosuppressive tumor microenvironment of these tumors. In this review article, we focus on PD-L1 expression and microsatellite instability (MSI) in PDAC, and their roles as prognostic and predictive markers. We also discuss data supporting combination therapies to augment cancer immunity cycle. Combining anti-PD-1/PD-L1 agents with other modalities such as vaccines, chemotherapy, and radiation could potentially overcome resistance patterns and increase immune responsiveness in PDAC.
Study on Cardiotoxicity and Mechanism of “Fuzi” Extracts Based on Metabonomics
Authors: Huang Guangyao , Yang Liang , Zhou Wei , Tang Xianglin , Wang Yuguang , Ma Zengchun , Gao Shan , Gao Yue
Published: November 2018

To investigate the toxicity of water and ethanol “Fuzi” (FZ) extracts and to explore the toxicity mechanism in rats. Water and ethanol extracts were prepared. Three groups of rats received the water extract, ethanol extract, or water by oral gavage for seven days. Pathological section staining of heart tissue. Colorimetric analysis was used to determine serum lactate dehydrogenase. The metabolic expression of small molecules in rats was measured by a metabolomics method. Western blotting was used to detect the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), transforming growth factor-β1 (TGF-β1), and caspase-3. Immunohistochemistry was used to detect the expression of CTnI, mTOR, and TGF-β1. The water and ethanol FZ extracts exert cardiotoxic effects via activating the PI3K/Akt/mTOR signaling pathway to induce cardiomyocyte apoptosis.
The Impact of Code Smells on Software Bugs: A Systematic Literature Review
Authors: Cairo Aloisio S. , Carneiro Glauco de F. , Monteiro Miguel P.
Published: November 2018

Context: Code smells are associated to poor design and programming style, which often degrades code quality and hampers code comprehensibility and maintainability. Goal: identify published studies that provide evidence of the influence of code smells on the occurrence of software bugs. Method: We conducted a Systematic Literature Review (SLR) to reach the stated goal. Results: The SLR selected studies from July 2007 to September 2017, which analyzed the source code of open source software projects and several code smells. Based on evidence of 16 studies covered in this SLR, we conclude that 24 code smells are more influential in the occurrence of bugs relative to the remaining smells analyzed. In contrast, three studies reported that at least 6 code smells are less influential in such occurrences. Evidence from the selected studies also point out tools, techniques, and procedures that should be applied to analyze the influence of the smells. Conclusions: To the best of our knowledge, this is the first SLR to target this goal. This study provides an up-to-date and structured understanding of the influence of code smells on the occurrence of software bugs based on findings systematically collected from a list of relevant references in the latest decade.
g-Good-Neighbor Diagnosability of Arrangement Graphs under the PMC Model and MM* Model
Authors: Wang Shiying , Ren Yunxia
Published: November 2018

Diagnosability of a multiprocessor system is an important research topic. The system and interconnection network has a underlying topology, which usually presented by a graph G = ( V , E ) . In 2012, a measurement for fault tolerance of the graph was proposed by Peng et al. This measurement is called the g-good-neighbor diagnosability that restrains every fault-free node to contain at least g fault-free neighbors. Under the PMC model, to diagnose the system, two adjacent nodes in G are can perform tests on each other. Under the MM model, to diagnose the system, a node sends the same task to two of its neighbors, and then compares their responses. The MM* is a special case of the MM model and each node must test its any pair of adjacent nodes of the system. As a famous topology structure, the ( n , k ) -arrangement graph A n , k , has many good properties. In this paper, we give the g-good-neighbor diagnosability of A n , k under the PMC model and MM* model.
Risk and Resilience at the Oroville Dam
Authors: Hollins Lucien X. , Eisenberg Daniel A. , Seager Thomas P.
Published: November 2018

Existing analyses of the February 2017 Oroville Dam Crisis identify maintenance failures and engineering shortcomings as the root cause of a nearly catastrophic failure of the tallest dam in the United States. However, the focus on technical shortcomings largely overlooks the role of adaptive decision-making that eventually averted the crisis. Understanding the decisions that both created the circumstances leading up to the crisis and saved the dam from collapse requires that risk analysis be complemented by a resilience perspective. This paper presents a case study on the Oroville Dam Crisis to develop a timeline of failures and successes in the resilience processes of sensing, anticipation, adapting, and learning throughout the history of the dam. Three factors that drove poor operational and engineering decisions include: (1) misalignment of technical nomenclature and design requirements for the ungated spillway, (2) overconfidence in original engineering designs, and (3) conflicting pressure from diverse stakeholders. These factors contributed to unrealistic perceptions of dam capabilities and promoted decisions to forgo maintenance and design efforts that may have mitigated the danger.
Associations among Bruxism, Gastroesophageal Reflux Disease, and Tooth Wear
Authors: Li Yuanyuan , Yu Fan , Niu Lina , Hu Wei , Long Yong , Tay Franklin R. , Chen Jihua
Published: November 2018

The relationship between bruxism and tooth wear is contentious in the literature. The pathophysiological processes of tooth wear may be complicated by the relationship between bruxism and gastroesophageal reflux disease (GERD). The objective of this study was to evaluate the associations among bruxism, GERD, and tooth wear. Two complementary studies were performed: a case-control study to verify the linkage between GERD and bruxism and a cross-sectional study on the same cohort to establish the connection between GERD and tooth wear in bruxism patients. A cohort of 363 consecutive bruxism patients and 363 matched control participants were recruited. Gastroesophageal reflux disease was diagnosed in accordance with the Montreal criteria. Tooth wear was scored based on the index recommended by Smith and Knight. Logistic regression analyses were performed. After adjustment, GERD was identified as a risk factor of bruxism. Bruxism with reflux symptoms for extensive time-periods was associated with severe tooth wear for the whole dentition (odds ratio, 4.70, 95% confidence interval, 2.04–10.83). Increased odds ratios for severe tooth wear were also found in all tooth locations and palatal/lingual and occlusal/incisal surfaces of bruxism patients with GERD for extensive time-periods. In conclusion, strong associations were identified among bruxism, GERD, and tooth wear.
A ‘Movement Screening Test’ of Functional Control Ability in Female Recreation Golfers and Non-Golfers over the Age of 80 Years: A Reliability Study
Authors: Webb Nicholas , Rowsome Keira , Ewings Sean , Comerford Mark , Stokes Maria , Mottram Sarah
Published: November 2018

Assessing function in elderly populations predominantly aims to quantify the risk of falling. Current assessment methods do not consider changes associated with aging in movement coordination patterns and the ability to control movement. The aim of this study was to examine the intra-rater reliability of a ‘Movement Screening Test’ (MST) in females over 80 years across a range of physical activity levels, who were golfers and non-golfers. Female recreational golfers (N = 21) and non-golfers (N = 10) aged 80 to 87 years performed the MST. The MST consists of three tests: Test 1, sit to stand with arm lift; Test 2, trunk lean with knee bend and opposite arm lift; Test 3, chest rotation with neutral head and pelvis. Videos of the MST were analyzed and scored according to specific criteria. The videos were reviewed on two separate occasions to quantify the intra-rater reliability of scoring of the MST. Intra-rater reliability ( κ ) of the MST demonstrated substantial agreement for 11/23 criteria ( κ = 0.65 and to 0.78) and excellent agreement for 9/23 criteria ( κ = 0.81 to 1). Therefore, the reliability of the MST for women aged 80 years and over was established. The MST test and scoring system may be further refined to improve reliability. Further investigations could explore coordination patterns in older people, how these relate to various aspects of musculoskeletal function, and how they vary between different populations.
Two-Dimensional Orthonormal Tree-Structured Haar Transform for Fast Block Matching
Authors: Ito Izumi , Egiazarian Karen
Published: November 2018

The goal of block matching (BM) is to locate small patches of an image that are similar to a given patch or template. This can be done either in the spatial domain or, more efficiently, in a transform domain. Full search (FS) BM is an accurate, but computationally expensive procedure. Recently introduced orthogonal Haar transform (OHT)-based BM method significantly reduces the computational complexity of FS method. However, it cannot be used in applications where the patch size is not a power of two. In this paper, we generalize OHT-based BM to an arbitrary patch size, introducing a new BM algorithm based on a 2D orthonormal tree-structured Haar transform (OTSHT). Basis images of OHT are uniquely determined from the full balanced binary tree, whereas various OTSHTs can be constructed from any binary tree. Computational complexity of BM depends on a specific design of OTSHT. We compare BM based on OTSHTs to FS and OHT (for restricted patch sizes) within the framework of image denoising, using WNNM as a denoiser. Experimental results on eight grayscale test images corrupted by additive white Gaussian noise with five noise levels demonstrate that WNNM with OTSHT-based BM outperforms other methods both computationally and qualitatively.
On the Dynamics of Canyon–Flow Interactions
Authors: Kämpf Jochen
Published: November 2018

This paper explores the dynamical origin and physical characteristics of flow disturbances induced by ocean currents in interaction with shelf-incised submarine canyons. To this end, a process-oriented hydrodynamic model is applied in a series of case studies. The focus of studies is the canyon-upwelling process in which seawater is moved from the upper continental slope onto the shelf within a shelf-break canyon. Results reveal that the generation of canyon upwelling, to zero-order approximation, is a barotropic and friction-independent quasi-geostrophic process. Hence, the principle of conservation of potential vorticity for such flows is sufficient to explain the fundamental physical properties of the canyon-upwelling process. For instance, this principle explains the direction-dependence of the canyon-upwelling process. This principle also explains the formation of stationary topographic Rossby waves downstream from the canyon that can lead to far-field effects. Density effects, being of secondary influence to the canyon-upwelling process, result in the intensification of canyon-upwelling flows via the formation of narrow near-bottom density fronts and associated baroclinic geostrophic frontal flows. Findings of this work reveal that the apparently complex canyon-upwelling process is much more basic than previously thought.
Improvements for the Eastern North Pacific ADCIRC Tidal Database (ENPAC15)
Authors: Szpilka Christine , Dresback Kendra , Kolar Randall , Massey T. Christopher
Published: November 2018

This research details the development and validation of the updated Eastern North Pacific (ENPAC) constituent tidal database, referred to as ENPAC15. The database was last updated in 2003 and was developed using the two-dimensional, depth integrated form of the ADvanced CIRCulation coastal hydrodynamic model, ADCIRC. Regional databases, such as ENPAC15, are capable of providing higher resolution near the coast, allowing users to more accurately define tidal forcing for smaller sub-regions. This study follows the same methodology as the EC2015 updates for the eastern coast of the United States and six main areas of improvement in the modeling configurations are examined: (1) placement of the open ocean boundary; (2) higher coastal resolution; (3) updated global bathymetry; (4) updated boundary forcing using two global tidal databases; (5) updated bottom friction formulations; and (6) improved model physics by incorporating the advective terms in ADCIRC. The skill of the improved database is compared to that of its predecessor and is calculated using harmonic data from three sources. Overall, the ENPAC15 database significantly (52% globally) reduces errors in the ENPAC03 database and improves the quality of tidal constituents available for sub-regional models in the ENPAC region.
Navigating Multiple Tensions for Engaged Praxis in a Complex Social-Ecological System
Authors: Cockburn Jessica , Palmer Carolyn (Tally) G. , Biggs Harry , Rosenberg Eureta
Published: November 2018

Innovative, pragmatic approaches are needed to support sustainable livelihoods and landscape management in complex social-ecological systems (CSES) such as river catchments. In the Tsitsa River Catchment, South Africa, researchers and natural resource managers have come together to apply such innovative approaches. Since CSES are characterised by uncertainty and surprise, understanding and managing them requires a commitment to reflexive praxis and transdisciplinarity. Accordingly, we facilitated a collective reflection and learning process in the project team to deepen our understanding of praxis in CSES. Our findings indicate that CSES thinking created an enabling framing. However, building new linkages among diverse actors to put CSES thinking into practice is challenging, since it requires the development of novel working relationships. Existing institutional structures, power dynamics, and ways of working impose significant constraints. A deeper critical realist analysis of our findings revealed a metaphor which explains why this work is challenging. In this metaphor, the Tsitsa Project team is navigating a bumpy terrain of dialectic tensions. These are tensions for example between natural science and social science, and between science and indigenous knowledge. Based on this metaphor, we suggest an expanding role for scientists and managers, and recommend transformative social learning processes to support teams navigating such bumpy terrains.
Exploring the Emergence of RNA Nucleosides and Nucleotides on the Early Earth
Authors: Biscans Annabelle
Published: November 2018

Understanding how life began is one of the most fascinating problems to solve. By approaching this enigma from a chemistry perspective, the goal is to define what series of chemical reactions could lead to the synthesis of nucleotides, amino acids, lipids, and other cellular components from simple feedstocks under prebiotically plausible conditions. It is well established that evolution of life involved RNA which plays central roles in both inheritance and catalysis. In this review, we present historically important and recently published articles aimed at understanding the emergence of RNA nucleosides and nucleotides on the early Earth.
Performance of Volcano-Like Laser Textured Cutting Tools: An Experimental and Simulative Investigation
Authors: Kang Zhengyang , Fu Yonghong , Fu Xingyu , Jun Martin Byung-Guk
Published: November 2018

In recent years, surface texturing in micro-scale has been attempted on the surface of cutting tools for multiple purposes, e.g., cutting force reduction, prolonging life-span, anti-adhesion, etc. With respect to machinability and performance, micro-groove texture (MGT) has dominated in this field compared to other textured patterns. In this study, a novel volcano-like texture (VLT) was fabricated on the rake face of cemented carbide inserts (WC-Co, YG6) by fiber laser. The following cutting experiment tested the flat, MGT and VLT tools in turning aluminum alloy 6061. The effects of coolant and cutting conditions were investigated. In addition, a validated FEM model was employed to explore the distribution of stress and temperature fields in the tool-chip interface. The initial forming process of adhesion layer on rake face was investigated as well. The results indicated that lower cutting force and less adhesion can be achieved by small scale VLT. This study not only introduced VLT on cutting tools but also revealed its comprehensive performance.
Regulating the Optoelectronic Properties of Nickel Dithiolene by the Substituents: A Theoretical Study
Authors: Sun Lili , Shu Siwei , Zhou Yi , Hou Sen , Liu Yan , Ke Zhuofeng
Published: November 2018

Dithiolene-based complexes show great potential to be applied as materials for organic optoelectronic devices. In this study, we theoretically designed a series of complexes based on nickel dithiolene and its substituted derivatives, the optoelectronic properties of which were comparatively studied by density functional theory (DFT)/time-dependent density functional theory (TD-DFT). The results show that the charge injection property of nickel dithiolene complexes can be significantly improved with introduction of electron-withdrawing groups. The charge transportation property of nickel dithiolene depends on the conjugation degree of the system. The energy gaps between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are determined by the substituents, which makes the maximum absorption wavelength red-shift from the visible to the near-infrared (NIR) region. The electron density difference graph shows that the electron transition from the ground state to the first excited state is assigned to π-π* transition mainly from HOMO to LUMO. The regularity of substituent effect revealed by us in this study will shed light on the application of nickel dithiolenes as potential optoelectronic materials.
Material Characterization of a Magnetorheological Fluid Subjected to Long-Term Operation in Damper
Authors: Utami Dewi , Ubaidillah  , Mazlan Saiful A. , Imaduddin Fitrian , Nordin Nur A. , Bahiuddin Irfan , Abdul Aziz Siti Aishah , Mohamad Norzilawati , Choi Seung-Bok
Published: November 2018

This paper investigates the field-dependent rheological properties of magnetorheological (MR) fluid used to fill in MR dampers after long-term cyclic operation. For testing purposes, a meandering MR valve was customized to create a double-ended MR damper in which MR fluid flowed inside the valve due to the magnetic flux density. The test was conducted for 170,000 cycles using a fatigue dynamic testing machine which has 20 mm of stroke length and 0.4 Hz of frequency. Firstly, the damping force was investigated as the number of operating cycles increased. Secondly, the change in viscosity of the MR fluid was identified as in-use thickening (IUT). Finally, the morphological observation of MR particles was undertaken before and after the long-term operation. From these tests, it was demonstrated that the damping force increased as the number of operating cycles increases, both when the damper is turn on (on-state) and off (off-state). It is also observed that the particle size and shape changed due to the long operation, showing irregular particles.