bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Vascular Patterns Using Contact Endoscopy and Narrow-Band Imaging (CE-NBI) for the Diagnosis of Vocal Fold Malignancy
Authors: Davaris Nikolaos , Lux Anke , Esmaeili Nazila , Illanes Alfredo , Boese Axel , Friebe Michael , Arens Christoph
Published: January 2020

The endoscopic detection of perpendicular vascular changes (PVC) of the vocal folds has been associated with vocal fold cancer, dysplastic lesions, and papillomatosis, according to a classification proposed by the European Laryngological Society (ELS). The combination of contact endoscopy with narrow-band imaging (NBI-CE) allows intraoperatively a highly contrasted, real-time visualization of vascular changes of the vocal folds. Aim of the present study was to determine the association of PVC to specific histological diagnoses, the level of interobserver agreement in the detection of PVC, and their diagnostic effectiveness in diagnosing laryngeal malignancy. The evaluation of our data confirmed the association of PVC to vocal fold cancer, dysplastic lesions, and papillomatosis. The level of agreement between the observers in the identification of PVC was moderate for the less-experienced observers and almost perfect for the experienced observers. The identification of PVC during NBI-CE proved to be a valuable indicator for diagnosing malignant and premalignant lesions.
Antiplatelet Drug Ticagrelor Enhances Chemotherapeutic Efficacy by Targeting the Novel P2Y12-AKT Pathway in Pancreatic Cancer Cells
Authors: Elaskalani Omar , Domenichini Alice , Abdol Razak Norbaini , E. Dye Danielle , Falasca Marco , Metharom Pat
Published: January 2020

Background: Extensive research has reported that extracellular ADP in the tumour microenvironment can stimulate platelets through interaction with the platelet receptor P2Y12. In turn, activated platelets release biological factors supporting cancer progression. Experimental data suggest that the tumour microenvironment components, of which platelets are integral, can promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Thus, overcoming chemoresistance requires combining multiple inhibitors that simultaneously target intrinsic pathways in cancer cells and extrinsic factors related to the tumour microenvironment. We aimed to determine whether ticagrelor, an inhibitor of the ADP–P2Y12 axis and a well-known antiplatelet drug, could be a therapeutic option for PDAC. Methods: We investigated a functional P2Y12 receptor and its downstream signalling in a panel of PDAC cell lines and non-cancer pancreatic cells termed hTERT-HPNE. We tested the synergistic effect of ticagrelor, a P2Y12 inhibitor, in combination with chemotherapeutic drugs (gemcitabine, paclitaxel and cisplatin), in vitro and in vivo. Results: Knockdown studies revealed that P2Y12 contributed to epidermal growth factor receptor (EGFR) activation and the expression of SLUG and ZEB1, which are transcriptional factors implicated in metastasis and chemoresistance. Studies using genetic and pharmacological inhibitors showed that the P2Y12–EGFR crosstalk enhanced cancer cell proliferation. Inhibition of P2Y12 signalling significantly reduced EGF-dependent AKT activation and promoted the anticancer activity of anti-EGFR treatment. Importantly, ticagrelor significantly decreased the proliferative capacity of cancer but not normal pancreatic cells. In vitro, synergism was observed when ticagrelor was combined with several chemodrugs. In vivo, a combination of ticagrelor with gemcitabine significantly reduced tumour growth, whereas gemcitabine or ticagrelor alone had a minimal effect. Conclusions: These findings uncover a novel effect and mechanism of action of the antiplatelet drug ticagrelor in PDAC cells and suggest a multi-functional role for ADP-P2Y12 signalling in the tumour microenvironment.
Prevention of DNA Replication Stress by CHK1 Leads to Chemoresistance Despite a DNA Repair Defect in Homologous Recombination in Breast Cancer
Authors: Meyer Felix , Becker Saskia , Classen Sandra , Parplys Ann Christin , Mansour Wael Yassin , Riepen Britta , Timm Sara , Ruebe Claudia , Jasin Maria , Wikman Harriet , Petersen Cordula , Rothkamm Kai , Borgmann Kerstin
Published: January 2020

Chromosomal instability not only has a negative effect on survival in triple-negative breast cancer, but also on the well treatable subgroup of luminal A tumors. This suggests a general mechanism independent of subtypes. Increased chromosomal instability (CIN) in triple-negative breast cancer (TNBC) is attributed to a defect in the DNA repair pathway homologous recombination. Homologous recombination (HR) prevents genomic instability by repair and protection of replication. It is unclear whether genetic alterations actually lead to a repair defect or whether superior signaling pathways are of greater importance. Previous studies focused exclusively on the repair function of HR. Here, we show that the regulation of HR by the intra-S-phase damage response at the replication is of overriding importance. A damage response activated by Ataxia telangiectasia and Rad3 related-checkpoint kinase 1 (ATR-CHK1) can prevent replication stress and leads to resistance formation. CHK1 thus has a preferred role over HR in preventing replication stress in TNBC. The signaling cascade ATR-CHK1 can compensate for a double-strand break repair error and lead to resistance of HR-deficient tumors. Established methods for the identification of HR-deficient tumors for Poly(ADP-Ribose)-Polymerase 1 (PARP1) inhibitor therapies should be extended to include analysis of candidates for intra-S phase damage response.
Exosomes in Bone Sarcomas: Key Players in Metastasis
Authors: Chicón-Bosch Mariona , Tirado Oscar M.
Published: January 2020

Bone sarcomas are rare cancers which often present with metastatic disease and are still associated with poor survival rates. Studies in the last decade have identified that exosomes, a type of extracellular vesicle released by cells, play an important role in tumour progression and dissemination. Through the transfer of their cargo (RNAs, proteins, and lipids) across cells, they are involved in cellular cross-talk and can induce changes in cellular behaviour. Exosomes have been shown to be important in metastasis organotropism, induction of angiogenesis and vascular permeability, the education of cells towards a pro-metastatic phenotype or the interaction between stromal and tumour cells. Due to the importance exosomes have in disease progression and the high incidence of metastasis in bone sarcomas, recent studies have evaluated the implications of these extracellular vesicles in bone sarcomas. In this review, we discuss the studies that evaluate the role of exosomes in osteosarcoma, Ewing sarcoma, and preliminary data on chondrosarcoma.
Urban Transformation: From Single-Point Solutions to Systems Innovation
Authors: Tonks Eleanor , Lockie Sean
Published: January 2020

Adapting our cities to the new climate regime is critical to ensure that human development is not jeopardized and that the world’s citizens can thrive where they live. Faced as we are with the imperative to act, we now need to accept that the challenges we face are not technical in nature—they are systemic. Traditionally, investments in low-carbon city solutions have suffered from being small and disaggregated, with a focus on single-point solutions. To truly enable city transformation at scale, we need to completely rewire our approach to urban innovation and implementation. To face our new reality, EIT Climate-KIC works on catalysing systems change through innovation in areas of human activity that have a critical impact on greenhouse gas emissions—cities, land use, materials, and finance—and to create climate-resilient communities. In this paper, EIT Climate-KIC reflects on its key learnings, as an innovation community, on how to apply innovation in service of urban transformation through the application of nature-based solutions.
The Potential Application of Ecklonia cava Extract in Scalp Protection
Authors: Kim Hayeon , Woo Hyunju , Shin Seoungwoo , Park Deokhoon , Jung Eunsun
Published: January 2020

The scalp is exposed to environmental hazards including airborne pollutants, which exert adverse effects on skin health. Therefore, compounds for defending skin from pollutants have attracted interest in the cosmeceutical community. We investigated whether Ecklonia cava exhibited prophylactic effects against urban pollutants by measuring cell viability and cell cycle distribution in human follicle dermal papilla cells (HFDPC). The effect of E. cava on pollutant-induced damage to skin barrier was determined by measuring filaggrin and MMP-1 expression in both keratinocytes and in a skin explant model. In a clinical trial, the effect of E. cava on scalp skin of patients with scalp scale was observed by evaluating hydration and redness after 4 weeks of daily treatment with a shampoo containing E. cava extract. E. cava extract recovered the loss of cell viability and abnormal cell cycle distribution induced by urban pollutants in HFDPCs. It also attenuated pollutant-induced damage to skin barrier by decreasing MMP-1 and increasing filaggrin expression in keratinocytes and the epidermis of skin explants. Moreover, E. cava showed soothing effects on human scalp by increasing hydration and decreasing redness in a clinical trial. Collectively, E. cava extract may be a good candidate for therapeutic applications designed to repair or protect hair scalp.
Applications of X-ray Powder Diffraction in Protein Crystallography and Drug Screening
Authors: Spiliopoulou Maria , Valmas Alexandros , Triandafillidis Dimitris-Panagiotis , Kosinas Christos , Fitch Andrew , Karavassili Fotini , Margiolaki Irene
Published: January 2020

Providing fundamental information on intra/intermolecular interactions and physicochemical properties, the three-dimensional structural characterization of biological macromolecules is of extreme importance towards understanding their mechanism of action. Among other methods, X-ray powder diffraction (XRPD) has proved its applicability and efficiency in numerous studies of different materials. Owing to recent methodological advances, this method is now considered a respectable tool for identifying macromolecular phase transitions, quantitative analysis, and determining structural modifications of samples ranging from small organics to full-length proteins. An overview of the XRPD applications and recent improvements related to the study of challenging macromolecules and peptides toward structure-based drug design is discussed. This review congregates recent studies in the field of drug formulation and delivery processes, as well as in polymorph identification and the effect of ligands and environmental conditions upon crystal characteristics. These studies further manifest the efficiency of protein XRPD for quick and accurate preliminary structural characterization.
35Cl NQR Relaxation of the Molecular Ferroelectric 5,6-Dichloro-2-Methylbenzimidazole with Hydrogen-Bonded Molecular Chain
Authors: Asaji Tetsuo
Published: January 2020

The 35Cl nuclear quadruple resonance (NQR) frequencies and spin-lattice relaxation times were measured in the temperature range of 4.2–420 K, of the above-room-temperature ferroelectric 5,6-dichloro-2-methylbenzimidazole, the ferroelectricity of which is thought to arise from the positional ordering of protons along chain of N-H...N hydrogen bonds. The first-order phase transition was clearly detected at around 400 K, as a discontinuity in the temperature dependence of NQR frequencies. The two NQR lines observed showed a much more significant difference in frequency in the high-temperature phase. This is consistent with the recently reported symmetry-lowering of crystal structure on warming. The relaxation mechanism in the low-temperature phase is discussed.
Does Land Use and Landscape Contribute to Self-Harm? A Sustainability Cities Framework
Authors: Vaz Eric , Shaker Richard Ross , Cusimano Michael D. , Loures Luis , Jokar Arsanjani Jamal
Published: January 2020

Self-harm has become one of the leading causes of mortality in developed countries. The overall rate for suicide in Canada is 11.3 per 100,000 according to Statistics Canada in 2015. Between 2000 and 2007 the lowest rates of suicide in Canada were in Ontario, one of the most urbanized regions in Canada. However, the interaction between land use, landscape and self-harm has not been significantly studied for urban cores. It is thus of relevance to understand the impacts of land-use and landscape on suicidal behavior. This paper takes a spatial analytical approach to assess the occurrence of self-harm along one of the densest urban cores in the country: Toronto. Individual self-harm data was gathered by the National Ambulatory Care System (NACRS) and geocoded into census tract divisions. Toronto’s urban landscape is quantified at spatial level through the calculation of its land use at different levels: (i) land use type, (ii) sprawl metrics relating to (a) dispersion and (b) sprawl/mix incidence; (iii) fragmentation metrics of (a) urban fragmentation and (b) density and (iv) demographics of (a) income and (b) age. A stepwise regression is built to understand the most influential factors leading to self-harm from this selection generating an explanatory model.
Acknowledgement to Reviewers of Drones in 2019
Authors:   Editorial Office
Published: January 2020

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...]
Dynamic Modeling of a Parallel-Connected Solid Oxide Fuel Cell Stack System
Authors: Wu Chien-Chang , Chen Tsung-Lin
Published: January 2020

This study proposes novel simulation methods to model the power delivery function of a parallel-connected solid-oxide-fuel-cell stack system. The proposed methods are then used to investigate the possible thermal runaway induced by the performance mismatch between the employed stacks. A challenge in this modeling study is to achieve the same output voltage but different output current for each employed stack. Conventional fuel-cell models cannot be used, because they employ fuel flow rates and stack currents as the input variables. These two variables are unknown in the parallel-connected stack systems. The proposed method solves the aforementioned problems by integrating the fuel supply dynamics with the conventional stack models and then arranging them in a multiple-feedback-loop configuration for conducting simulations. The simulation results indicate that the proposed methods can model the transient response of the parallel-connected stack system. Moreover, for the dynamics of the power distribution, there exists an unstable positive feedback loop between employed stacks when the stack temperatures are low, and a stable negative feedback loop when the stack temperatures are high. A thermal runaway could be initiated when the dynamics of the stack temperature is slower than that of the current distribution.
Taguchi Method and Numerical Simulation for Variable Viscosity and Non-Linear Boussinesq Effects on Natural Convection over a Vertical Truncated Cone in Porous Media
Authors: Tu Ken Ming , Yih Kuo Ann , Chou Fu I , Chou Jyh Horng
Published: January 2020

This study uses an optimization approach representation and numerical solution for the variable viscosity and non-linear Boussinesq effects on the free convection over a vertical truncated cone in porous media. The surface of the vertical truncated cone is maintained at uniform wall temperature and uniform wall concentration (UWT/UWC). The viscosity of the fluid varies inversely to a linear function of the temperature. The partial differential equation is transformed into a non-similar equation and solved by Keller box method (KBM). Compared with previously published articles, the results are considered to be very consistent. Numerical results for the local Nusselt number and local Sherwood number with the six parameters (1) dimensionless streamwise coordinate ξ, (2) buoyancy ratio N, (3) Lewis number Le, (4) viscosity-variation parameter θ r , (5) non-linear temperature parameter δ 1 , and (6) non-linear concentration parameter δ 2 are expressed in figures and tables. The Taguchi method was used to predict the best point of the maxima of the local Nusselt (Sherwood) number of 3.8636 (5.1156), resulting in ξ (4), N (10), Le (0.5), θ r (−2), δ 1 (2), δ 2 (2) and ξ (4), N (10), Le (2), θ r (−2), δ 1 (2), δ 2 (2), respectively.
Optimal Energy Storage System Positioning and Sizing with Robust Optimization
Authors: Chowdhury Nayeem , Pilo Fabrizio , Pisano Giuditta
Published: January 2020

Energy storage systems can improve the uncertainty and variability related to renewable energy sources such as wind and solar create in power systems. Aside from applications such as frequency regulation, time-based arbitrage, or the provision of the reserve, where the placement of storage devices is not particularly significant, distributed storage could also be used to improve congestions in the distribution networks. In such cases, the optimal placement of this distributed storage is vital for making a cost-effective investment. Furthermore, the now reached massive spread of distributed renewable energy resources in distribution systems, intrinsically uncertain and non-programmable, together with the new trends in the electric demand, often unpredictable, require a paradigm change in grid planning for properly lead with the uncertainty sources and the distribution system operators (DSO) should learn to support such change. This paper considers the DSO perspective by proposing a methodology for energy storage placement in the distribution networks in which robust optimization accommodates system uncertainty. The proposed method calls for the use of a multi-period convex AC-optimal power flow (AC-OPF), ensuring a reliable planning solution. Wind, photovoltaic (PV), and load uncertainties are modeled as symmetric and bounded variables with the flexibility to modulate the robustness of the model. A case study based on real distribution network information allows the illustration and discussion of the properties of the model. An important observation is that the method enables the system operator to integrate energy storage devices by fine-tuning the level of robustness it willing to consider, and that is incremental with the level of protection. However, the algorithm grows more complex as the system robustness increases and, thus, it requires higher computational effort.
Multi-Objective Particle Swarm Optimization Algorithm for Multi-Step Electric Load Forecasting
Authors: Yang Yi , Shang Zhihao , Chen Yao , Chen Yanhua
Published: January 2020

As energy saving becomes more and more popular, electric load forecasting has played a more and more crucial role in power management systems in the last few years. Because of the real-time characteristic of electricity and the uncertainty change of an electric load, realizing the accuracy and stability of electric load forecasting is a challenging task. Many predecessors have obtained the expected forecasting results by various methods. Considering the stability of time series prediction, a novel combined electric load forecasting, which based on extreme learning machine (ELM), recurrent neural network (RNN), and support vector machines (SVMs), was proposed. The combined model first uses three neural networks to forecast the electric load data separately considering that the single model has inevitable disadvantages, the combined model applies the multi-objective particle swarm optimization algorithm (MOPSO) to optimize the parameters. In order to verify the capacity of the proposed combined model, 1-step, 2-step, and 3-step are used to forecast the electric load data of three Australian states, including New South Wales, Queensland, and Victoria. The experimental results intuitively indicate that for these three datasets, the combined model outperforms all three individual models used for comparison, which demonstrates its superior capability in terms of accuracy and stability.
Adaptation of Forest Trees to Rapidly Changing Climate
Authors: Kijowska-Oberc Joanna , Staszak Aleksandra M. , Kamiński Jan , Ratajczak Ewelina
Published: January 2020

Climate change leads to global drought-induced stress and increased plant mortality. Tree species living in rapidly changing climate conditions are exposed to danger and must adapt to new climate conditions to survive. Trees respond to changes in the environment in numerous ways. Physiological modulation at the seed stage, germination strategy and further development are influenced by many different factors. We review forest abiotic threats (such as drought and heat), including biochemical responses of plants to stress, and biotic threats (pathogens and insects) related to global warming. We then discus the varied adaptations of tree species to changing climate conditions such as seed resistance to environmental stress, improved by an increase in temperature, affinity to specific fungal symbionts, a wide range of tolerance to abiotic environmental conditions in the offspring of populations occurring in continental climate, and germination strategies closely linked to the ecological niche of the species. The existing studies do not clearly indicate whether tree adaptations are shaped by epigenetics or phenology and do not define the role of phenotypic plasticity in tree development. We have created a juxtaposition of literature that is useful in identifying the factors that play key roles in these processes. We compare scientific evidence that species distribution and survival are possible due to phenotypic plasticity and thermal memory with studies that testify that trees’ phenology depends on phylogenesis, but this issue is still open. It is possible that studies in the near future will bring us closer to understanding the mechanisms through which trees adapt to stressful conditions, especially in the context of epigenetic memory in long-lived organisms, and allow us to minimize the harmful effects of climatic events by predicting tree species’ responses or by developing solutions such as assisted migration to mitigate the consequences of these phenomena.
Investigating the Temporal Relationships between Symptoms and Nebuliser Adherence in People with Cystic Fibrosis: A Series of N-of-1 Observations
Authors: Martin Rosie , Arden Madelynne , Porritt Jenny , Wildman Martin , Naughton Felix
Published: January 2020

Treatment adherence in adults with cystic fibrosis (CF) is poor. One of the reasons identified for lack of adherence to nebulised treatments is that patients may not experience any immediate relief in their symptoms or notice changes as a result of taking their treatment, thus many report that they do not perceive there to be consequences of non adherence. The aim of the study was to investigate the temporal relationships between symptoms and adherence to nebulised treatments in adults with CF using an N-of-1 observational design. Six participants were recruited for a six-week period during which time they completed a daily online respiratory symptom questionnaire. Adherence to treatment was measured throughout the duration of the study using an eTrack® nebuliser that logged date and time of treatments taken. Data generated from each participant was analysed separately. There were significant relationships between pain and adherence for three participants, tiredness and adherence for one participant and cough and adherence for one participant. For all of these findings, the symptom and adherence were experienced on the same day. Extending the monitoring period beyond six weeks may provide increased insight into the complex relationship between symptoms and adherence in CF.
Can Active Video Games Improve Physical Activity in Adolescents? A Review of RCT
Authors: Williams Wanda M. , Ayres Cynthia G.
Published: January 2020

Children and adolescents are not meeting the required federal physical activity (PA) guidelines established by the United States Department of Health and Human Services. It is critical that a regular pattern of PA is established in their youth to ensure ongoing PA into adulthood. However, many programs implemented during adolescence have shown limited effects, stressing the need for more innovative approaches to generate more interest and maintenance of PA behavior in this age group. Active video games (AVGs) or exergaming may prove to be an innovate process to improve PA in children and adolescents. A literature review was conducted to explore if active video games or exergaming could be an effective intervention to improve physical activity in adolescents. Active video games, also called “exergames”, are a category of video games that require movement or physical exertion to play the game. The methodology consisted of searching Academic Search Premier, CINAHL, The Cochrane Library, ERIC, PubMed, and Web of Science databases. Inclusion criteria involved only youth aged 12 to 19 years, randomized controlled trials (RCTs), and studies within the last 12 years. The following search terms were used: exergaming or active video games; physical activity or exercise; adolescents or youth; RCT or randomized clinical trial. The outcome indicates that exergaming or active video games can be an effective tool to improve PA in adolescents that will be more acceptable and sustainable than many conventional approaches.
Evacuate or Stay? A Typhoon Evacuation Decision Model in China Based on the Evolutionary Game Theory in Complex Networks
Authors: Sun Dian , Zhang Lupeng , Su Zifeng
Published: January 2020

The Chinese Government has played an important role in organizing the evacuation of typhoon disasters, and in-depth analysis of individual behavioral decisions is a prerequisite for adopting an effective emergency organization plan. Existing evacuation plans only consider how the Government issues the early warning and organizes the mandatory evacuation, but does not formulate effective policies to improve the efficiency of self-evacuation of evacuees and lacks the understanding of individual evacuation decision-making. Using game-based theory in a small-world network context, we build an evolutionary game model of evacuation decision diffusion between evacuees in the context of a complex network. The model simulates the effects of guaranteeing the evacuation order and providing material supplies on the evacuation decision diffusion in a small-world network in China. The results showed that various levels of policy-implementation led to different rates of evacuation. As the cost-reduction of the evacuation process increased, the evacuation response rate in the social system increased. In contrast, as the rate of reducing the non-evacuation cost decreased or the cost-reduction rate of non-evacuation increased, the evacuation response rate in the social system decreased. The study findings provided insights on emergency planning and the effectiveness of their implementation in social networks, which can be used to improve evacuation policy.
Alcohol Outlet Density and Deprivation in Six Towns in Bergrivier Municipality before and after Legislative Restrictions
Authors: Bowers Yasmin , Davids Adlai , London Leslie
Published: January 2020

Introduction. In 2016, after the Western Cape Liquor Act was enacted, alcohol outlets were mapped in the six towns from a previous 2008 study to determine: (1) alcohol outlet density; (2) the association between deprivation and alcohol outlet density; (3) geospatial trends of alcohol outlet densities; and (4) the impact of alcohol legislation. Methods. Latitude and longitude coordinates were collected of legal and illegal alcohol outlets, and alcohol outlet density was calculated for legal, illegal and total alcohol outlets by km2 and per 1000 persons. To determine the impact of legislation, t-tests and hot spot analyses were calculated for both 2008 and 2016 studies. Spearman coefficients estimated the relationship between alcohol outlet density and deprivation. Results. Although not statistically significant, the number of alcohol outlets and the density per 1000 population declined by about 12% and 34%, respectively. Illegal outlets were still more likely to be located in more deprived areas, and legal outlets in less deprived areas; and a reduction or addition of a few outlets can change a town’s hot spot status. Conclusions. Further studies with larger sample sizes might help to clarify the impacts of the Liquor Act, and the more recent 2017 Alcohol-Related Harms Reduction Policy on alcohol outlet density in the province.
Sonic Hedgehog Regulates Bone Fracture Healing
Authors: Takebe Hiroaki , Shalehin Nazmus , Hosoya Akihiro , Shimo Tsuyoshi , Irie Kazuharu
Published: January 2020

Bone fracture healing involves the combination of intramembranous and endochondral ossification. It is known that Indian hedgehog (Ihh) promotes chondrogenesis during fracture healing. Meanwhile, Sonic hedgehog (Shh), which is involved in ontogeny, has been reported to be involved in fracture healing, but the details had not been clarified. In this study, we demonstrated that Shh participated in fracture healing. Six-week-old Sprague–Dawley rats and Gli-CreERT2; tdTomato mice were used in this study. The right rib bones of experimental animals were fractured. The localization of Shh and Gli1 during fracture healing was examined. The localization of Gli1 progeny cells and osterix (Osx)-positive cells was similar during fracture healing. Runt-related transcription factor 2 (Runx2) and Osx, both of which are osteoblast markers, were observed on the surface of the new bone matrix and chondrocytes on day seven after fracture. Shh and Gli1 were co-localized with Runx2 and Osx. These findings suggest that Shh is involved in intramembranous and endochondral ossification during fracture healing.
Review of Alterations in Perlecan-Associated Vascular Risk Factors in Dementia
Authors: Trout Amanda L. , Rutkai Ibolya , Biose Ifechukwude J. , Bix Gregory J.
Published: January 2020

Perlecan is a heparan sulfate proteoglycan protein in the extracellular matrix that structurally and biochemically supports the cerebrovasculature by dynamically responding to changes in cerebral blood flow. These changes in perlecan expression seem to be contradictory, ranging from neuroprotective and angiogenic to thrombotic and linked to lipid retention. This review investigates perlecan’s influence on risk factors such as diabetes, hypertension, and amyloid that effect Vascular contributions to Cognitive Impairment and Dementia (VCID). VCID, a comorbidity with diverse etiology in sporadic Alzheimer’s disease (AD), is thought to be a major factor that drives the overall clinical burden of dementia. Accordingly, changes in perlecan expression and distribution in response to VCID appears to be injury, risk factor, location, sex, age, and perlecan domain dependent. While great effort has been made to understand the role of perlecan in VCID, additional studies are needed to increase our understanding of perlecan’s role in health and in cerebrovascular disease.
The Probiotic BB12 Induces MicroRNAs Involved in Antigen Processing and Presentation in Porcine Monocyte-Derived Dendritic Cells
Authors: Bravo-Parra Marlene , Arenas-Padilla Marina , Bárcenas-Preciado Valeria , Hernández Jesús , Mata-Haro Verónica
Published: January 2020

MicroRNAs (miRNAs) mediate the regulation of gene expression. Several reports indicate that probiotics induce miRNA-mediated immunomodulation at different levels, such as cytokine production and the up-regulation of several markers related to antigen presentation in antigen-presenting cells. The objective of this work was to identify target genes of miRNAs that are involved in the processing and presentation of antigens in monocyte-derived dendritic cells (moDCs) stimulated with the probiotic Bifidobacterium animalis ssp. lactis BB12 (BB12). First, an in silico prediction analysis for a putative miRNA binding site within a given mRNA target was performed using RNAHybrid software with mature sequences of differentially expressed miRNAs retrieved from a Genbank data set that included BB12-stimulated and unstimulated porcine monocytes. From them, 23 genes resulted in targets of 19 miRNAs, highlighting miR-30b-3p, miR-671-5p, and miR-9858-5p, whose targets were costimulatory molecules, and were overexpressed (p < 0.05) in BB12-stimulated moDCs. The analysis of moDCs showed that the percentage of cells expressing SLA-DR+CD80+ decreased significantly (p = 0.0081) in BB12-stimulated moDCs; interleukin (IL)-10 production was unchanged at 6 h but increased after 24 h of culture in the presence of BB12 (p < 0.001). In summary, our results suggest that SLA-DR and CD80 can be down-regulated by miRNAs miR-30b-3p, miR-671-5p, and miR-9858-5p, while miR-671-5p targets IL-10.
Revealing and Harnessing Tumour-Associated Microglia/Macrophage Heterogeneity in Glioblastoma
Authors: Pires-Afonso Yolanda , Niclou Simone P. , Michelucci Alessandro
Published: January 2020

Cancer heterogeneity and progression are subject to complex interactions between neoplastic cells and their microenvironment, including the immune system. Although glioblastomas (GBMs) are classified as ‘cold tumours’ with very little lymphocyte infiltration, they can contain up to 30–40% of tumour-associated macrophages, reported to contribute to a supportive microenvironment that facilitates tumour proliferation, survival and migration. In GBM, tumour-associated macrophages comprise either resident parenchymal microglia, perivascular macrophages or peripheral monocyte-derived cells. They are recruited by GBMs and in turn release growth factors and cytokines that affect the tumour. Notably, tumour-associated microglia/macrophages (TAMs) acquire different expression programs, which shape the tumour microenvironment and contribute to GBM molecular subtyping. Further, emerging evidence highlights that TAM programs may adapt to specific tumour features and landscapes. Here, we review key evidence describing TAM transcriptional and functional heterogeneity in GBM. We propose that unravelling the intricate complexity and diversity of the myeloid compartment as well as understanding how different TAM subsets may affect tumour progression will possibly pave the way to new immune therapeutic avenues for GBM patients.
Manifestation of Systemic Toxicity in Rats after a Short-Time Inhalation of Lead Oxide Nanoparticles
Authors: Sutunkova Marina P. , Solovyeva Svetlana N. , Chernyshov Ivan N. , Klinova Svetlana V. , Gurvich Vladimir B. , Shur Vladimir Ya. , Shishkina Ekaterina V. , Zubarev Ilya V. , Privalova Larisa I. , Katsnelson Boris A.
Published: January 2020

Outbred female rats were exposed to inhalation of lead oxide nanoparticle aerosol produced right then and there at a concentration of 1.30 ± 0.10 mg/m3 during 5 days for 4 h a day in a nose-only setup. A control group of rats were sham-exposed in parallel under similar conditions. Even this short-time exposure of a relatively low level was associated with nanoparticles retention demonstrable by transmission electron microscopy in the lungs and the olfactory brain. Some impairments were found in the organism’s status in the exposed group, some of which might be considered lead-specific toxicological outcomes (in particular, increase in reticulocytes proportion, in δ-aminolevulinic acid (δ-ALA) urine excretion, and the arterial hypertension’s development).
Identification and Pilot Evaluation of Salivary Peptides from Anopheles albimanus as Biomarkers for Bite Exposure and Malaria Infection in Colombia
Authors: Londono-Renteria Berlin , Drame Papa M. , Montiel Jehidys , Vasquez Ana M. , Tobón-Castaño Alberto , Taylor Marissa , Vizcaino Lucrecia , Lenhart Audrey E.
Published: January 2020

Insect saliva induces significant antibody responses associated with the intensity of exposure to bites and the risk of disease in humans. Several salivary biomarkers have been characterized to determine exposure intensity to Old World Anopheles mosquito species. However, new tools are needed to quantify the intensity of human exposure to Anopheles bites and understand the risk of malaria in low-transmission areas in the Americas. To address this need, we conducted proteomic and bioinformatic analyses of immunogenic candidate proteins present in the saliva of uninfected Anopheles albimanus from two separate colonies—one originating from Central America (STECLA strain) and one originating from South America (Cartagena strain). A ~65 kDa band was identified by IgG antibodies in serum samples from healthy volunteers living in a malaria endemic area in Colombia, and a total of five peptides were designed from the sequences of two immunogenic candidate proteins that were shared by both strains. ELISA-based testing of human IgG antibody levels against the peptides revealed that the transferrin-derived peptides, TRANS-P1, TRANS-P2 and a salivary peroxidase peptide (PEROX-P3) were able to distinguish between malaria-infected and uninfected groups. Interestingly, IgG antibody levels against PEROX-P3 were significantly lower in people that have never experienced malaria, suggesting that it may be a good marker for mosquito bite exposure in naïve populations such as travelers and deployed military personnel. In addition, the strength of the differences in the IgG levels against the peptides varied according to location, suggesting that the peptides may able to detect differences in intensities of bite exposure according to the mosquito population density. Thus, the An. albimanus salivary peptides TRANS-P1, TRANS-P2, and PEROX-P3 are promising biomarkers that could be exploited in a quantitative immunoassay for determination of human-vector contact and calculation of disease risk.
Protective Effects of [6]-Gingerol Against Chemical Carcinogens: Mechanistic Insights
Authors: Furlan Veronika , Bren Urban
Published: January 2020

[6]-Gingerol from ginger has received considerable attention as a potential cancer therapeutic agent because of its chemopreventive and chemotherapeutic effects, as well as its safety. In the current study, we examined [6]-gingerol as a natural scavenger of nine ultimate chemical carcinogens to which we are frequently exposed: glycidamide, styrene oxide, aflatoxin B1 exo-8,9-epoxide, β-propiolactone, ethylene oxide, propylene oxide, 2-cyanoethylene oxide, chloroethylene oxide, and vinyl carbamate epoxide. To evaluate [6]-gingerol efficacy, we expanded our research with the examination of glutathione—the strongest natural scavenger in human cells. The corresponding activation free energies were calculated using Hartree-Fock method with three flexible basis sets and two implicit solvation models. According to our results, [6]-gingerol proves to be an extremely effective scavenger of chemical carcinogens of the epoxy type. On the other hand, with the exception of aflatoxin B1 exo-8,9-epoxide, glutathione represents a relatively poor scavenger, whose efficacy could be augmented by [6]-gingerol. Moreover, our quantum mechanical study of the alkylation reactions of chemical carcinogens with [6]-gingerol and glutathione provide valuable insights in the reaction mechanisms and the geometries of the corresponding transition states. Therefore, we strongly believe that our research forms a solid basis for further computational, experimental and clinical studies of anticarcinogenic properties of [6]-gingerol as well as for the development of novel chemoprophylactic dietary supplements. Finally, the obtained results also point to the applicability of quantum chemical methods to studies of alkylation reactions related to chemical carcinogenesis.
Potential Clinical Implications of miR-1 and miR-21 in Heart Disease and Cardioprotection
Authors: Kura Branislav , Kalocayova Barbora , Devaux Yvan , Bartekova Monika
Published: January 2020

The interest in non-coding RNAs, which started more than a decade ago, has still not weakened. A wealth of experimental and clinical studies has suggested the potential of non-coding RNAs, especially the short-sized microRNAs (miRs), to be used as the new generation of therapeutic targets and biomarkers of cardiovascular disease, an ever-growing public health issue in the modern world. Among the hundreds of miRs characterized so far, microRNA-1 (miR-1) and microRNA-21 (miR-21) have received some attention and have been associated with cardiac injury and cardioprotection. In this review article, we summarize the current knowledge of the function of these two miRs in the heart, their association with cardiac injury, and their potential cardioprotective roles and biomarker value. While this field has already been extensively studied, much remains to be done before research findings can be translated into clinical application for patient’s benefit.
The TUSC2 Tumour Suppressor Inhibits the Malignant Phenotype of Human Thyroid Cancer Cells via SMAC/DIABLO Protein
Authors: Mariniello Raffaela Mariarosaria , Maria Orlandella Francesca , De Stefano Anna Elisa , Iervolino Paola Lucia Chiara , Smaldone Giovanni , Luciano Neila , Cervone Nara , Munciguerra Francesco , Esposito Silvia , Mirabelli Peppino , Salvatore Giuliana
Published: January 2020

Thyroid carcinoma is the most common endocrine cancer and includes different forms. Among these, anaplastic thyroid carcinoma (ATC) is the rarest but the most lethal subtype, compared to papillary thyroid carcinoma (PTC) which shows an overall good prognosis. We have previously showed that Tumor Suppressor Candidate 2 (TUSC2), a known tumour suppressor gene, is downregulated in human PTC and ATC compared to normal thyroid samples. The aim of this study was to gain insight into the molecular mechanisms induced by TUSC2 in thyroid cancer cells. Here, we stably transfected TUSC2 in papillary (TPC-1) and in anaplastic (8505C) thyroid cancer cell lines and studied its effects on several biological processes, demonstrating that TUSC2 overexpression decreased thyroid cancer cell proliferation, migration and invasion. Through the proteome profiler apoptosis array, we observed that TUSC2 increased sensitivity to apoptosis by increasing the SMAC/DIABLO and CYTOCHROME C proteins. On the other hand, transient silencing of TUSC2, by siRNA, in an immortalized thyroid follicular epithelial cell line (Nthy-ori 3-1) showed the opposite effect. Finally modulation of SMAC/DIABLO partially rescued the biological effects of TUSC2. Thus, our data highlight a tumour suppressor role of TUSC2 in thyroid carcinogenesis, suggesting that it could be a promising target and biomarker for thyroid carcinoma.
The Flagellar Gene Regulates Biofilm Formation and Mussel Larval Settlement and Metamorphosis
Authors: Liang Xiao , Zhang Xiu-Kun , Peng Li-Hua , Zhu You-Ting , Yoshida Asami , Osatomi Kiyoshi , Yang Jin-Long
Published: January 2020

Biofilms are critical components of most marine systems and provide biochemical cues that can significantly impact overall community composition. Although progress has been made in the bacteria–animal interaction, the molecular basis of modulation of settlement and metamorphosis in most marine animals by bacteria is poorly understood. Here, Pseudoalteromonas marina showing inducing activity on mussel settlement and metamorphosis was chosen as a model to clarify the mechanism that regulates the bacteria–mussel interaction. We constructed a flagellin synthetic protein gene fliP deletion mutant of P. marina and checked whether deficiency of fliP gene will impact inducing activity, motility, and extracellular polymeric substances of biofilms. Furthermore, we examined the effect of flagellar proteins extracted from bacteria on larval settlement and metamorphosis. The deletion of the fliP gene caused the loss of the flagella structure and motility of the ΔfliP strain. Deficiency of the fliP gene promoted the biofilm formation and changed biofilm matrix by reducing β-polysaccharides and increasing extracellular proteins and finally reduced biofilm-inducing activities. Flagellar protein extract promoted mussel metamorphosis, and ΔfliP biofilms combined with additional flagellar proteins induced similar settlement and metamorphosis rate compared to that of the wild-type strain. These findings provide novel insight on the molecular interactions between bacteria and mussels.
Strength Assessment of Rectangular Plates Subjected to Extreme Cyclic Load Reversals
Authors: Tekgoz Mesut , Garbatov Yordan
Published: January 2020

The objective of this study is to investigate the strength of the rectangular plates subjected to cyclic load reversals with varying strain ranges. The finite element solution is implemented to estimate the load-carrying capacity. The influence of the initial imperfections, plate thicknesses and aspect ratio parameters have been accounted for. The cyclic response is predicted by using the material model assumed to follow the combined non-linear isotropic and kinematic strain hardening rules with Von Misses yield criterion accounting for the Bauschinger effect. It has been shown that the type of plastic formation during the cyclic load has a significant influence on the structural capacity and stiffness reduction. The initial imperfection has a significant impact on the ultimate load capacity reduction where the uni-modal initial imperfection type leads to a more stable load transition and plastic formation, reducing the structural capacity during the cyclic load exposure.
Influence of Milling Time on the Homogeneity and Magnetism of a Fe70Zr30 Partially Amorphous Alloy: Distribution of Curie Temperatures
Authors: Manchón-Gordón Alejandro F. , Ipus Jhon J. , Blázquez Javier S. , Conde Clara F. , Conde Alejandro
Published: January 2020

In this work, the mechanically alloyed Fe70Zr30 (at. %) composition has been used to study the influence of milling time on its homogeneity and magnetic properties. The microstructure and Fe environment results show the formation of an almost fully amorphous alloy after 50 h of milling in a mixture of pure 70 at. % Fe and 30 at. % Zr. The soft magnetic behavior of the samples enhances with the increase of the milling time, which is ascribed to the averaging out of the magnetocrystalline anisotropy as the crystal size decreases and the amorphous fraction increases. The formation of a non-perfectly homogenous system leads to a certain compositional heterogeneity, motivating the existence of a distribution of Curie temperatures. The parameters of the distribution (the average Curie temperature, T C ¯ , and the broadening of the distribution, ∆ T C ) have been obtained using a recently reported procedure, based on the analysis of the approach towards the saturation curves and the magnetocaloric effect. The decrease of ∆ T C and the increase of T C ¯ with the milling time are in agreement with the microstructural results. As the remaining α-Fe phase decreases, the amorphous matrix is enriched in Fe atoms, enhancing its magnetic response.
A Review on Membrane Technology and Chemical Surface Modification for the Oily Wastewater Treatment
Authors: Yalcinkaya Fatma , Boyraz Evren , Maryska Jiri , Kucerova Klara
Published: January 2020

Cleaning of wastewater for the environment is an emerging issue for the living organism. The separation of oily wastewater, especially emulsified mixtures, is quite challenged due to a large amount of wastewater produced in daily life. In this review, the membrane technology for oily wastewater treatment is presented. In the first part, the global membrane market, the oil spill accidents and their results are discussed. In the second and third parts, the source of oily wastewater and conventional treatment methods are represented. Among all methods, membrane technology is considered the most efficient method in terms of high separation performance and easy to operation process. In the fourth part, we provide an overview of membrane technology, fouling problem, and how to improve the self-cleaning surface using functional groups for effectively treating oily wastewater. The recent development of surface-modified membranes for oily wastewater separation is investigated. It is believed that this review will promote understanding of membrane technology and the development of surface modification strategies for anti-fouling membranes.