bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of an Acetic Acid and Acetone Mixture on the Characteristics and Scaffold–Cell Interaction of Electrospun Polycaprolactone Membranes
Authors: Ho Minh Hieu , Do Thien Bui-Thuan , Dang Nhi Ngoc-Thao , Le An Nguyen-My , Ta Hanh Thi-Kieu , Vo Toi Van , Nguyen Hiep Thi
Published: October 2019

Green electrospinning has attracted great interest since non-toxic solvents were shown to be applicable in the fabrication of fibrous materials while ensuring health safety and environmental protection. Less harmful reagents such as acetone (AC) and acetic acid (AA) have been employed in this field in recent years. However, research in this area is still rare, yielding only preliminary results. In this study, two different types of solvents (pure AC and an AA/AC mixture) were used to fabricate electrospun polycaprolactone (PCL) membranes. Sample morphology, wettability, tensile strength, and chemical composition were compared between two types of membranes. Cell–scaffold interaction was also examined by cell adhesion and proliferation assays. The results demonstrate that the two types of solvents had significant effects on membrane morphology, physical strength, and cell adherence behaviors, which should be considered for different application purposes.
Properties of Phase Solitons in an Optically Driven Semiconductor Ring Laser
Authors: Shakarab Ghafour Hashemvand , Kheradmand Reza , Bolorizadeh Mohammad Agha , Prati Franco
Published: October 2019

A semiconductor ring laser with a long cavity supports propagating localised structures with a chiral charge, named phase solitons. In this paper we study the dependence of the velocity and of the duration of the phase solitons on the characteristic time scales of the laser, namely the photon lifetime and the carrier lifetime. We show numerically that phase solitons are stable over a large range of those parameters and verify that the propagation velocity decreases linearly with the ratio of the carrier lifetime to the photon lifetime, while the duration is proportional to the ratio of the carrier lifetime to the cavity roundtrip time.
Deep Learning Object-Impulse Detection for Enhancing Leakage Detection of a Boiler Tube Using Acoustic Emission Signal
Authors: Duong Bach Phi , Kim Jaeyoung , Kim Cheol-Hong , Kim Jong-Myon
Published: October 2019

Advances in technology have enhanced the ability to detect leakages in boiler tube components in thermal power plants. As a specific issue, the interaction between the coal fuel stream and the boiler tube membrane generates random and high-amplitude impulses, which negatively affect the measured acoustic emission (AE) signal from leakages. It is essential to detect and practically handle these kinds of impulses. Based on the object detection concept, this paper proposes an impulse detection methodology that employs deep learning flexible boundary regression (DLFBR). First, the shape extraction (SE) preprocessing technique is implemented to yield the shape signal, which contains intrinsic information about the impulse from the raw AE signal. Then, DLFBR extracts and generates both the feature map and the confidence mask from the shape signal to regress a boundary box, which specifies the position of the impulse. For illustration purposes, the proposed algorithm is applied to an experimental leakage detection dataset recorded from a subcritical boiler unit with a tube membrane. Experimental results show that the proposed method is effective for detecting impulses of leakage in a boiler tube testbed, providing 99.8% average classification accuracy.
Retrieval of Nearshore Bathymetry around Ganquan Island from LiDAR Waveform and QuickBird Image
Authors: Zhang Zhen , Zhang Jingyu , Ma Yi , Tian Huibo , Jiang Tao
Published: October 2019

Optical remote sensing is an effective means of water depth measurement, but the current approach of mainstream bathymetric retrieval requires a large amount of onsite measurement data. Such data are hard to obtain from places where underwater terrains are complicated and unsteady, and from sea areas affected by issues with rights and conflicts of interest. In recent years, the emergence of airborne light detection and ranging (LiDAR) provided a new technical means for field bathymetric survey. In this study, water depth inversion was carried out around an island far from the mainland by using remote sensing images and real LiDAR waveform data. Multi-Gaussian function fitting was proposed to extract water depth data from waveform data, and bathymetric values were used as control and validation data of the active and passive combination of water depth inversion. Results show that the relative error was 5.6% for the bathymetric retrieval from LiDAR waveform data, and the accuracy meets the requirements of ocean bathymetry. The average relative error of water depth inversion based on active and passive remote sensing was less than 9%. The method used in this study can also reduce the use of LiDAR data and the cost, thus providing a new idea for future coastal engineering application and construction.
Utilizing Energy Storage for Reliability Solutions in Active Distribution Systems
Authors: Gautam Prajjwal , Piya Prasanna , Karki Rajesh
Published: October 2019

Stochastic failures in a distribution network result in different reliability events, such as voltage sags and momentary and sustained interruptions, causing significant financial losses for many customers. Strategic utilization of energy storage system (ESS) can help mitigate these reliability events. This paper investigates the role of ESS toward providing reliability solutions in the context of an active distribution system. In this regard, scenario-based probabilistic modeling of reliability event mitigation with the ESS is presented, which is integrated into the reliability evaluation framework. The proposed approach is efficient in assessing reliability solutions with ESS considering storage technology type, power/energy rating, hardware availability, presence of other distributed energy resources, etc. A range of case studies is conducted to evaluate mitigation of reliability events at a different level of the distribution system. Valuable insights into the efficient utilization of ESS are provided based on findings.
Evaluation of Biochar and Compost Mixes as Substitutes to a Commercial Propagation Mix
Authors: Huang Lan , Yu Ping , Gu Mengmeng
Published: October 2019

The effects of biochar (BC) on seed propagation depend on the type of BC, BC incorporation rate, base substrate, and plant seed species. Limited research tested BC-compost mixes for seed propagation. High percentages (70% or 80%, by volume) of BC with vermicompost (VC) or chicken manure compost (CM) were evaluated to substitute a commercial propagation mix (control) in three experiments. Seeds, including basil, coleus, edamame, marigold, okra, petunia, radish, salvia, tomato, vinca, and zinnia in Experiments 1 and 2 had similar or higher emergence percentages (EPs) and emergence indexes (EIs) in both BC:VC mixes, while celosia, cowpea, corn, and pumpkin had lower EPs or EIs in either 8BC:2VC or 7BC:3VC mixes compared to the control. Seedling fresh weights in both BC:VC mixes were similar to the control except for vinca, pumpkin, marigold, and salvia. The BC:VC mixes had no negative effects on plant dry weights at 7 weeks after transplanting. In Experiment 3, BC:CM mixes suppressed the seed germination or seedling growth of coleus, corn, cowpea, marigold, petunia, pumpkin, radish, salvia, vinca, watermelon, and zinnia due to high pH and CM’s high electrical conductivity. Therefore, 7BC:3VC and 8BC:2VC can be used as seed propagation mix, while 7BC:3CM and 8BC:2CM are not recommended.
A Novel Time Constraint-Based Approach for Knowledge Graph Conflict Resolution
Authors: Wang Yanjun , Qiao Yaqiong , Ma Jiangtao , Hu Guangwu , Zhang Chaoqin , Sangaiah Arun Kumar , Zhang Hongpo , Ren Kai
Published: October 2019

Knowledge graph conflict resolution is a method to solve the knowledge conflict problem in constructing knowledge graphs. The existing methods ignore the time attributes of facts and the dynamic changes of the relationships between entities in knowledge graphs, which is liable to cause high error rates in dynamic knowledge graph construction. In this article, we propose a knowledge graph conflict resolution method, knowledge graph evolution algorithm based on deep learning (Kgedl), which can resolve facts confliction with high precision by combing time attributes, semantic embedding representations, and graph structure features. Kgedl first trains the semantic embedding vector through the relationships between entities. Then, the path embedding vector is trained from the graph structures of knowledge graphs, and the time attributes of entities are combined with the semantic and path embedding vectors. Finally, Kgedl uses a recurrent neural network to make the inconsistent facts appear in the dynamic evolution of the knowledge graph consistent. A large number of experiments on real datasets show that Kgedl outperforms the state-of-the-art methods. Especially, Kgedl achieves 23% higher performance than the classical method numerical Probabilistic Soft Logic (nPSL).in the metric HITS@10. Also, extensive experiments verified that our proposal possess better robustness by adding noise data.
Smart System for the Retrieval of Digital Educational Content
Authors: Gil Ana B. , de la Prieta Fernando , Rodríguez Sara , Corchado Juan M.
Published: October 2019

The education sector is a major generator, consumer, and depositary of educational content. Thanks to technological advances, today’s educators and learners have ubiquitous and on-demand access to information. Technology has made it possible for us to communicate and share information effortlessly from anywhere in the world. However, the availability of vast amounts of heterogeneous educational content will not be useful unless we search, retrieve and integrate it, creating interoperable educational environments. The current challenges to integrating educational content arise from its distribution over several repositories. This research proposes AIREH (architecture for intelligent retrieval of educational content from heterogeneous environments), for the retrieval of digital content through agent-based virtual organizations. This flexible architecture facilitates the search for and integration of heterogeneous content through an information retrieval model that involves both case-based reasoning and federated search. Moreover, AIREH is based on an adaptive organization model for distributed planning, thanks to which, it manages open systems flexibly, dynamically, and effectively. The conducted case study gives very promising results and demonstrates the advantages of using agent-based virtual organizations in the retrieval of labeled digital content. The proposed model is flexible, customizable, comprehensive and efficient.
Extracellular Oxygen Sensors Based on PtTFPP and Four-Arm Block Copolymers
Authors: Qiao Yuan , Pan Tingting , Li Jiaze , Yang Cheng , Wen Jiaxing , Zhong Ke , Wu Shanshan , Su Fengyu , Tian Yanqing
Published: October 2019

Three four-arm amphiphilic block copolymers with different chain lengths, consisting of a hydrophilic chain of polyethylene glycol (PEG) and hydrophobic segment of polycaprolactam (PCL), were synthesized and used to encapsulate the high-efficient and hydrophobic oxygen probe of platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin (PtTFPP) to form polymer micelles. This approach enabled the use of PtTFPP in aqueous solution for biosensing. Experimental results demonstrated that the particle sizes of these nano-oxygen sensors between 40.0 and 203.8 nm depend on the structures of block copolymers. PtTFPP in these micelles showed an effective quantum yield under nitrogen environment, ranging from 0.06 to 0.159. The new sensors are suitable for analyzing dissolved oxygen concentrations in the range of 0.04–39.3 mg/L by using the linear Stern–Volmer equation at room temperature. In addition, it has been shown that these sensors are capable of in situ monitoring the dissolved oxygens in the culture medium of E. coli and Romas cells during the respiration process, and distinguishing the drug activity of antibiotic ampicillin from that of antimycin A. This study showed that the use of these nanostructured multi-arm block copolymer micelles can achieve efficient biological applications without specific structural modification of the hydrophobic PtTFPP probe, which is expected to have broad prospects.
The Influence of Synoptic-Scale Air Mass Conditions on Seasonal Precipitation Patterns over North Carolina
Authors: Zarzar Christopher , Dyer Jamie
Published: October 2019

This paper characterizes the influence of synoptic-scale air mass conditions on the spatial and temporal patterns of precipitation in North Carolina over a 16-year period (2003–2018). National Center for Environmental Prediction Stage IV multi-sensor precipitation estimates were used to describe seasonal variations in precipitation in the context of prevailing air mass conditions classified using the spatial synoptic classification system. Spatial analyses identified significant clustering of high daily precipitation amounts distributed along the east side of the Appalachian Mountains and along the Coastal Plains. Significant and heterogeneous clustering was prevalent in summer months and tended to coincide with land cover boundaries and complex terrain. The summer months were dominated by maritime tropical air mass conditions, whereas dry moderate air mass conditions prevailed in the winter, spring, and fall. Between the three geographic regions of North Carolina, the highest precipitation amounts were received in western North Carolina during the winter and spring, and in eastern North Carolina in the summer and fall. Central North Carolina received the least amount of precipitation; however, there was substantial variability between regions due to prevailing air mass conditions. There was an observed shift toward warmer and more humid air mass conditions in the winter, spring, and fall months throughout the study period (2003–2018), indicating a shift toward air mass conditions conducive to higher daily average rain rates in North Carolina.
Characterization of Multitermination CG Flashes Using a 3D Lightning Mapping System (FALMA)
Authors: Gao Panliang , Wang Daohong , Shi Dongdong , Wu Ting , Takagi Nobuyuki
Published: October 2019

We characterized 205 multiple-termination negative cloud-to-ground (CG) lightning flashes that were imaged by the Fast Antenna Lightning Mapping Array (FALMA) in Japan during the summer of 2017. The parameters we used included termination number, termination distance, fork height, return stroke (RS) number, the interval between the first RS of each termination, the shortest time difference between the strokes at different terminations, and the first RS intensities separated by termination occurrence orders. It was found that the multiple-termination flashes (MTFs) had a termination number ranging from 2 to 5, with the majority (148/205) at 2. The termination distance (with high probability) was between 2 and 4 km, with 10 out of 359 MTF termination distances being longer than 10 km. For most MTFs (146/205), their leader forks for different terminations occurred at a height between 4 and 6 km, indicating that the fork process mainly occurred inside the cloud. The RS number of the MTFs ranged from 2 to 18, with an arithmetic mean (AM) value of 5.8. The interval between the first RS of each termination in the MTFs ranged from 0.5 to 965.3 ms, with an AM value of 225.6 ms, while the shortest time difference between the strokes at different terminations had an AM value of 189.6 ms. The intensity of the first stroke in each termination tended to decrease with increasing termination occurrence orders.
Review of PM Oxidative Potential Measured with Acellular Assays in Urban and Rural Sites across Italy
Authors: Pietrogrande Maria Chiara , Russo Mara , Zagatti Elisa
Published: October 2019

This work is an overview of the oxidative potential (OP) values up to date measured in Italy, with the aim to provide a picture of the spatial and seasonal variability of OP in the various geographical areas across Italy. The summarized works used the common acellular assays-based dithiothreitol (OPDTT), ascorbic acid (OPAA), glutathione (OPGSH), and 2′,7′-dichlorodfluorescein (OPDCFH) assays. The paper describes the association of OP responses with PM chemical composition, the sensitivity of various acellular OP assays to PM components and emission sources, and PM size distribution of the measured OP values. Our synthesis indicates that crustal and transition metals (e.g., Fe, Ni, Cu, Cr, Mn, Zn, and V), secondary ions and carbonaceous components (elemental carbon, EC, organic carbon, OC and water soluble carbon, WSOC) show significant correlations with OP across different urban and rural areas and size ranges. These chemical species are mainly associated with various PM sources, including residual/fuel oil combustion, traffic emissions, and secondary organic aerosol formation. Although the OP assays are sensitive to the same redox-active species, they differ in the association with PM chemical components. The DDT assay is mainly sensitive to the organic compounds that are mostly accumulated in the fine PM fraction, i.e., tracers of burning sources, and redox active organics associated with other markers of photochemical aging. In contrast, OPAA and OPGSH were mostly responsive to metals, mainly those related to non-exhaust traffic emissions (Cu, Zn, Cr, Fe, Ni, Mn, Sn, Cd, Pb), that are mainly accumulated in the coarse PM. Among the investigated sites, our synthesis shows larger OP values in Trentino region and the Po Valley, that may be explained by the high density of anthropogenic sources, and the orographic and meteorological characteristics, that favor the pollutants accumulation and aerosol photo-oxidative aging.
Characterization of Moisture Sources for Austral Seas and Relationship with Sea Ice Concentration
Authors: Reboita Michelle Simões , Nieto Raquel , da Rocha Rosmeri P. , Drumond Anita , Vázquez Marta , Gimeno Luis
Published: October 2019

In this study, the moisture sources acting over each sea (Weddell, King Haakon VII, East Antarctic, Amundsen-Bellingshausen, and Ross-Amundsen) of the Southern Ocean during 1980–2015 are identified with the FLEXPART Lagrangian model and by using two approaches: backward and forward analyses. Backward analysis provides the moisture sources (positive values of Evaporation minus Precipitation, E − P > 0), while forward analysis identifies the moisture sinks (E − P < 0). The most important moisture sources for the austral seas come from midlatitude storm tracks, reaching a maximum between austral winter and spring. The maximum in moisture sinks, in general, occurs in austral end-summer/autumn. There is a negative correlation (higher with 2-months lagged) between moisture sink and sea ice concentration (SIC), indicating that an increase in the moisture sink can be associated with the decrease in the SIC. This correlation is investigated by focusing on extremes (high and low) of the moisture sink over the Weddell Sea. Periods of high (low) moisture sinks show changes in the atmospheric circulation with a consequent positive (negative) temperature anomaly contributing to decreasing (increasing) the SIC over the Weddell Sea. This study also suggests possible relationships between the positive (negative) phase of the Southern Annular Mode with the increase (decrease) in the moisture that travels from the midlatitude sources to the Weddell Sea.
Bioengineering Liver Transplantation
Authors: Verstegen Monique M.A. , Spee Bart , van der Laan Luc J.W.
Published: October 2019

Since the first in-man liver transplantation was performed by Starzl et al [...]
Suppression of Sclerotinia sclerotiorum by the Induction of Systemic Resistance and Regulation of Antioxidant Pathways in Tomato Using Fengycin Produced by Bacillus amyloliquefaciens FZB42
Authors: Farzand Ayaz , Moosa Anam , Zubair Muhammad , Khan Abdur Rashid , Massawe Venance Colman , Tahir Hafiz Abdul Samad , Sheikh Taha Majid Mahmood , Ayaz Muhammad , Gao Xuewen
Published: October 2019

Lipopeptides from Bacillus species exhibit promising biological control activity against plant pathogens. This study aimed to explore the potential of purified fengycin to induce systemic resistance in tomato against Sclerotinia sclerotiorum. Bacillus amyloliquefaciens FZB42, its mutant AK1S, and their corresponding metabolites showed in vitro inhibition of S. sclerotiorum mycelium. Fengycin derived from an AK1S mutant was purified and identified through HPLC and MALDI-TOF-MS, respectively. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed structural deformities in the fungal mycelium. Moreover, fengycin induced the accumulation of reactive oxygen species (ROS) in S. sclerotiorum mycelium and downregulated the expression of ROS-scavenging genes viz., superoxide dismutase (SsSOD1), peroxidase (SsPO), and catalase (SsCAT1) compared to the untreated control. Furthermore, the lesion size was dramatically reduced in fengycin-treated tomato plants compared to plants infected with S. sclerotiorum only in a greenhouse experiment. Additionally, the transcriptional regulation of defense-related genes GST, SOD, PAL, HMGR, and MPK3 showed the highest upsurge in expression at 48 h post-inoculation (hpi). However, their expression was subsequently decreased at 96 hpi in fengycin + S. sclerotiorum treatment compared to the plants treated with fengycin only. Conversely, the expression of PPO increased in a linear manner up to 96 hpi.
Fructans as Immunomodulatory and Antiviral Agents: The Case of Echinacea
Authors: Dobrange Erin , Peshev Darin , Loedolff Bianke , Van den Ende Wim
Published: October 2019

Throughout history, medicinal purposes of plants have been studied, documented, and acknowledged as an integral part of human healthcare systems. The development of modern medicine still relies largely on this historical knowledge of the use and preparation of plants and their extracts. Further research into the human microbiome highlights the interaction between immunomodulatory responses and plant-derived, prebiotic compounds. One such group of compounds includes the inulin-type fructans (ITFs), which may also act as signaling molecules and antioxidants. These multifunctional compounds occur in a small proportion of plants, many of which have recognized medicinal properties. Echinacea is a well-known medicinal plant and products derived from it are sold globally for its cold- and flu-preventative and general health-promoting properties. Despite the well-documented phytochemical profile of Echinacea plants and products, little research has looked into the possible role of ITFs in these products. This review aims to highlight the occurrence of ITFs in Echinacea derived formulations and the potential role they play in immunomodulation.
An Efficient Agrobacterium Mediated Transformation of Pineapple with GFP-Tagged Protein Allows Easy, Non-Destructive Screening of Transgenic Pineapple Plants
Authors: Priyadarshani S. V. G. N. , Cai Hanyang , Zhou Qiao , Liu Yanhui , Cheng Yan , Xiong Junjie , Patson Dikoko Lesego , Cao Shijiang , Zhao Heming , Qin Yuan
Published: October 2019

Quite a few studies have been conducted to improve the Agrobacterium-mediated transformation of pineapple, which is the second most important commercial tropical fruit crop worldwide. However, pineapple transformation remains challenging, due to technical difficulties, the lengthy regeneration process, and a high labor requirement. There have not been any studies specifically addressing the introduction of GFP-tagged genes into pineapples through Agrobacterium-mediated transformation, which would enable easy, non-destructive expression detection. It would also allow expression localization at the organelle level, which is not possible with GUS a reporter gene that encodes β-glucuronidase or a herbicide resistance reporter gene. Here, we report a method for the introduction of GFP-tagged genes into pineapples through Agrobacterium-mediated transformation. We used embryonic calli for transformation, and plants were regenerated through somatic embryogenesis. In this study, we optimized the incubation time for Agrobacterium infection, the co-cultivation time, the hygromycin concentration for selection, and the callus growth conditions after selection. Our strategy reduced the time required to obtain transgenic plants from 7.6 months to 6.1 months. The expression of GFP-tagged AcWRKY28 was observed in the nuclei of transgenic pineapple root cells. This method allows easy, non-destructive expression detection of transgenic constructs at the organelle level. These findings on pineapple transformation will help accelerate pineapple molecular breeding efforts to introduce new desirable traits.
Status of Plant Protein-Based Green Scaffolds for Regenerative Medicine Applications
Authors: Jahangirian Hossein , Azizi Susan , Rafiee-Moghaddam Roshanak , Baratvand Bahram , Webster Thomas J.
Published: October 2019

In recent decades, regenerative medicine has merited substantial attention from scientific and research communities. One of the essential requirements for this new strategy in medicine is the production of biocompatible and biodegradable scaffolds with desirable geometric structures and mechanical properties. Despite such promise, it appears that regenerative medicine is the last field to embrace green, or environmentally-friendly, processes, as many traditional tissue engineering materials employ toxic solvents and polymers that are clearly not environmentally friendly. Scaffolds fabricated from plant proteins (for example, zein, soy protein, and wheat gluten), possess proper mechanical properties, remarkable biocompatibility and aqueous stability which make them appropriate green biomaterials for regenerative medicine applications. The use of plant-derived proteins in regenerative medicine has been especially inspired by green medicine, which is the use of environmentally friendly materials in medicine. In the current review paper, the literature is reviewed and summarized for the applicability of plant proteins as biopolymer materials for several green regenerative medicine and tissue engineering applications.
Pre- and Post-Treatment with Novel Antiepileptic Drug Oxcarbazepine Exerts Neuroprotective Effect in the Hippocampus in a Gerbil Model of Transient Global Cerebral Ischemia
Authors: Ahn Ji Hyeon , Shin Bich Na , Park Joon Ha , Lee Tae-Kyeong , Park Young Eun , Lee Jae-Chul , Yang Go Eun , Shin Myoung Cheol , Cho Jun Hwi , Lee Kyu Chang , Won Moo-Ho , Kim Hyeyoung
Published: October 2019

Oxcarbazepine, an antiepileptic drug, has been reported to modulate voltage-dependent sodium channels, and it is commonly used in epilepsy treatment. In this study, we investigated the neuroprotective effect of oxcarbazepine in the hippocampus after transient ischemia in gerbils. Gerbils randomly received oxcarbazepine 100 or 200 mg/kg before and after transient ischemia. We examined its neuroprotective effect in the cornu ammonis 1 subfield of the gerbil hippocampus at 5 days after transient ischemia by using cresyl violet staining, neuronal nuclei immunohistochemistry and Fluoro-Jade B histofluorescence staining for neuroprotection, and by using glial fibrillary protein and ionized calcium-binding adapter molecule 1 immunohistochemistry for reaction of astrocytes and microglia, respectively. Pre- and post-treatment with 200 mg/kg of oxcarbazepine, but not 100 mg/kg of oxcarbazepine, protected pyramidal neurons of the cornu ammonis 1 subfield from transient ischemic damage. In addition, pre- and post-treatment with oxcarbazepine (200 mg/kg) significantly ameliorated astrocytes and microglia activation in the ischemic cornu ammonis 1 subfield. In brief, our current results indicate that post-treatment as well as pre-treatment with 200 mg/kg of oxcarbazepine can protect neurons from ischemic insults via attenuation of the glia reaction.
The Many Facets of Tumor Heterogeneity: Is Metabolism Lagging Behind?
Authors: Loponte Sara , Lovisa Sara , Deem Angela K. , Carugo Alessandro , Viale Andrea
Published: October 2019

Tumor functional heterogeneity has been recognized for decades, and technological advancements are fueling renewed interest in uncovering the cell-intrinsic and extrinsic factors that influence tumor development and therapeutic response. Intratumoral heterogeneity is now arguably one of the most-studied topics in tumor biology, leading to the discovery of new paradigms and reinterpretation of old ones, as we aim to understand the profound implications that genomic, epigenomic, and functional heterogeneity hold with regard to clinical outcomes. In spite of our improved understanding of the biological complexity of cancer, characterization of tumor metabolic heterogeneity has lagged behind, lost in a century-old controversy debating whether glycolysis or mitochondrial respiration is more influential. But is tumor metabolism really so simple? Here, we review historical and current views of intratumoral heterogeneity, with an emphasis on summarizing the emerging data that begin to illuminate just how vast the spectrum of metabolic strategies a tumor can employ may be, and what this means for how we might interpret other tumor characteristics, such as mutational landscape, contribution of microenvironmental influences, and treatment resistance.
The Complexities of Metastasis
Authors: San Juan Beatriz P. , Garcia-Leon Maria J. , Rangel Laura , Goetz Jacky G. , Chaffer Christine L.
Published: October 2019

Therapies that prevent metastatic dissemination and tumor growth in secondary organs are severely lacking. A better understanding of the mechanisms that drive metastasis will lead to improved therapies that increase patient survival. Within a tumor, cancer cells are equipped with different phenotypic and functional capacities that can impact their ability to complete the metastatic cascade. That phenotypic heterogeneity can be derived from a combination of factors, in which the genetic make-up, interaction with the environment, and ability of cells to adapt to evolving microenvironments and mechanical forces play a major role. In this review, we discuss the specific properties of those cancer cell subgroups and the mechanisms that confer or restrict their capacity to metastasize.
CAF-1 Subunits Levels Suggest Combined Treatments with PARP-Inhibitors and Ionizing Radiation in Advanced HNSCC
Authors: Morra Francesco , Merolla Francesco , Picardi Ida , Russo Daniela , Ilardi Gennaro , Varricchio Silvia , Liotti Federica , Pacelli Roberto , Palazzo Luca , Mascolo Massimo , Celetti Angela , Staibano Stefania
Published: October 2019

Oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas show high morbidity and mortality rates. We aimed to investigate the role of the “Chromatin Assembly Factor-1” (CAF-1) p60 and p150 subunits, involved in DNA repair and replication, in OSCC and OPSCC progression and in response to Poly(ADP-ribose) polymerase (PARP)-inhibitors and exposure to ionizing radiation (IR). We immunostained tissue microarrays (TMAs), including 112 OSCC and 42 OPSCC, with anti-CAF-1/p60 and anti-CAF-1/p150 specific antibodies, correlating their expression with prognosis. Moreover, we assessed the sensitivity to PARP inhibitors and the double-strand breaks repair proficiency by cell viability and HR reporter assays, respectively, in HPV-positive and HPV-negative cell lines upon CAF-1/p60 and CAF-1/p150 depletion. The immunohistochemical analysis revealed a significant prognostic value of both tissue biomarkers combined expression in OSCC but not in OPSCC. In in vitro studies, the p60/150 CAF-1 subunits’ depletion impaired the proficiency of Homologous Recombination DNA damage repair, inducing sensitivity to the PARP-inhibitors, able to sensitize both the cell lines to IR. These results indicate that regardless of the prognostic meaning of p60/p150 tissue expression, the pharmacological depletion of CAF-1 complex’s function, combined to PARP-inhibitors and/or IR treatment, could represent a valid therapeutic strategy for squamous cell carcinomas of head and neck region.
CD200 Induces Epithelial-to-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma via β-Catenin-Mediated Nuclear Translocation
Authors: Shin Seung-Phil , Goh Ah Ra , Kang Hyeon-Gu , Kim Seok-Jun , Kim Jong-Kwang , Kim Kyung-Tae , Lee John H , Bae Yong-Soo , Jung Yuh-Seog , Lee Sang-Jin
Published: October 2019

The membrane glycoprotein CD200 binds to its receptor CD200R1 and induces tolerance, mainly in cells of the myeloid lineage; however, information regarding its role in solid tumors is limited. Here, we investigated whether CD200 expression, which is enriched mainly in high-grade head and neck squamous cell carcinoma (HNSCC), correlates with cancer progression, particularly the epithelial-to-mesenchymal transition (EMT). The forced overexpression of CD200 in the HNSCC cell line, UMSCC84, not only increased the expression of EMT-related genes, but also enhanced invasiveness. The cleaved cytoplasmic domain of CD200 interacted with β-catenin in the cytosol, was translocated to the nucleus, and eventually enhanced EMT-related gene expression. CD200 increased the invasiveness of mouse tonsillar epithelium immortalized with E6, E7, and Ras (MEER), a model of tonsillar squamous cell carcinoma. siRNA inhibition of CD200 or extracellular domain of CD200R1 down-regulated the expression of EMT-related genes and decreased invasiveness. Consistently, compared to CD200-null MEER tumors, subcutaneous CD200-expressing MEER tumors showed significantly increased metastatic migration into draining lymph nodes. Our study demonstrates a novel and unique role of CD200 in inducing EMT, suggesting the potential therapeutic target for blocking solid cancer progression.
Chaperone-Mediated Autophagy and Its Emerging Role in Hematological Malignancies
Authors: Robert Guillaume , Jacquel Arnaud , Auberger Patrick
Published: October 2019

Chaperone-mediated autophagy (CMA) ensures the selective degradation of cellular proteins endowed with a KFERQ-like motif by lysosomes. It is estimated that 30% of all cellular proteins can be directed to the lysosome for CMA degradation, but only a few substrates have been formally identified so far. Mechanistically, the KFERQ-like motifs present in substrate proteins are recognized by the molecular chaperone Hsc70c (Heat shock cognate 71 kDa protein cytosolic), also known as HSPA8, and directed to LAMP2A, which acts as the CMA receptor at the lysosomal surface. Following linearization, the protein substrate is next transported to the lumen of the lysosomes, where it is degraded by resident proteases, mainly cathepsins and eventually recycled to sustain cellular homeostasis. CMA is induced by different stress conditions, including energy deprivation that also activates macro-autophagy (MA), that may make it difficult to decipher the relative impact of both pathways on cellular homeostasis. Besides common inducing triggers, CMA and MA might be induced as compensatory mechanisms when either mechanism is altered, as it is the often the case in different pathological settings. Therefore, CMA activation can compensate for alterations of MA and vice versa. In this context, these compensatory mechanisms, when occurring, may be targeted for therapeutic purposes. Both processes have received particular attention from scientists and clinicians, since modulation of MA and CMA may have a profound impact on cellular proteostasis, metabolism, death, differentiation, and survival and, as such, could be targeted for therapeutic intervention in degenerative and immune diseases, as well as in cancer, including hematopoietic malignancies. The role of MA in cancer initiation and progression is now well established, but whether and how CMA is involved in tumorigenesis has been only sparsely explored. In the present review, we encompass the description of the mechanisms involved in CMA, its function in the physiology and pathogenesis of hematopoietic cells, its emerging role in cancer initiation and development, and, finally, the potential therapeutic opportunity to target CMA or CMA-mediated compensatory mechanisms in hematological malignancies.
β-Endorphin Induction by Psychological Stress Promotes Leydig Cell Apoptosis through p38 MAPK Pathway in Male Rats
Authors: Xiong Xiaofan , Zhang Lingyu , Fan Meiyang , Han Lin , Wu Qiuhua , Liu Siyuan , Miao Jiyu , Liu Liying , Wang Xiaofei , Guo Bo , Tong Dongdong , Ni Lei , Yang Juan , Huang Chen
Published: October 2019

Psychological stress (PS) disturbs the reproductive endocrine system and promotes male infertility, but the underlying pathogenic mechanisms have not been extensively studied. This study aimed to uncover the mechanisms of PS-induced male reproductive related abnormalities subjected to a ‘terrified sound’ exposure. Male rats subjected to PS displayed slow growth, decreased sperm quality, abnormal levels of the reproductive endocrine hormones, decreased expression of the reproductive-related proteins androgen-binding protein (ABP) and bromodomain-containing protein (BRDT), increased apoptosis in the testis, and accompanied by elevated levels of β-endorphin (β-EP). These effects were reversed by naloxone. Furthermore, PS-induced β-EP could promote mu opioid receptor (MOR) activation and ensure intracellular p38 MAPK phosphorylation and then lead to Leydig cells (LCs) apoptosis. The current result showed that β-EP was a key factor to PS-induced male infertility.
The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study
Authors: Kuo Kuan-Lin , Liu Shing-Hwa , Lin Wei-Chou , Chow Po-Ming , Chang Yu-Wei , Yang Shao-Ping , Shi Chung-Sheng , Hsu Chen-Hsun , Liao Shih-Ming , Chang Hong-Chiang , Huang Kuo-How
Published: October 2019

After chemotherapy for the treatment of metastatic bladder urothelial carcinoma (UC), most patients inevitably encounter drug resistance and resultant treatment failure. Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins and play a critical role in maintaining protein homeostasis. This study investigated the antitumor effect of PR-619, a DUBs inhibitor, in combination with cisplatin, for bladder UC treatment. Our results showed that PR-619 effectively induced dose- and time-dependent cytotoxicity, apoptosis, and ER-stress related apoptosis in human UC (T24 and BFTC-905) cells. Additionally, co-treatment of PR-619 with cisplatin potentiated cisplatin-induced cytotoxicity in UC cells and was accompanied by the concurrent suppression of Bcl-2. We also proved that Bcl-2 overexpression is related to the chemo-resistant status in patients with metastatic UC by immunohistochemistry (IHC) staining. In a xenograft mice model, we confirmed that PR-619 enhanced the antitumor effect of cisplatin on cisplatin-naïve and cisplatin-resistant UCs. Our results demonstrated that PR-619 effectively enhanced the cisplatin-induced antitumor effect via concurrent suppression of the Bcl-2 level. These findings provide promising insight for developing a therapeutic strategy for UC treatment.
Use of Human Pluripotent Stem Cells to Define Initiating Molecular Mechanisms of Cataract for Anti-Cataract Drug Discovery
Authors: Dewi Chitra Umala , O’Connor Michael D.
Published: October 2019

Cataract is a leading cause of blindness worldwide. Currently, restoration of vision in cataract patients requires surgical removal of the cataract. Due to the large and increasing number of cataract patients, the annual cost of surgical cataract treatment amounts to billions of dollars. Limited access to functional human lens tissue during the early stages of cataract formation has hampered efforts to develop effective anti-cataract drugs. The ability of human pluripotent stem (PS) cells to make large numbers of normal or diseased human cell types raises the possibility that human PS cells may provide a new avenue for defining the molecular mechanisms responsible for different types of human cataract. Towards this end, methods have been established to differentiate human PS cells into both lens cells and transparent, light-focusing human micro-lenses. Sensitive and quantitative assays to measure light transmittance and focusing ability of human PS cell-derived micro-lenses have also been developed. This review will, therefore, examine how human PS cell-derived lens cells and micro-lenses might provide a new avenue for development of much-needed drugs to treat human cataract.
Development of Vitroceramic Coatings and Analysis of Their Suitability for Biomedical Applications
Authors: Jinga Sorin-Ion , Skokin Michael , Vasile Bogdan-Stefan , Constantinoiu Izabela , Miu Dana , Bacalum Mihaela , Busuioc Cristina
Published: October 2019

Within the field of tissue engineering, thin films have been studied to improve implant fixation of metallic or ceramic materials in bone, connective tissue, oral mucosa or skin. In this context, to enhance their suitability as implantable devices, titanium-based substrates received a superficial vitroceramic coating by means of laser ablation. Further, this study describes the details of fabrication and corresponding tests in order to demonstrate the bioactivity and biocompatibility of the newly engineered surfaces. Thus, the metallic supports were covered with a complex material composed of SiO2, P2O5, CaO, MgO, ZnO and CaF2, in the form of thin layers via a physical deposition techniques, namely pulsed laser deposition. The resulting products were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning and transmission electron microscopy coupled with energy dispersive X-ray spectroscopy, selected area electron diffraction, and electron energy loss spectroscopy. It was found that a higher substrate temperature and a lower working pressure lead to the highest quality film. Finally, the samples biocompatibility was assessed and they were found to be bioactive after simulated body fluid soaking and biocompatible through the MTT cell viability test.
The Corrosion Resistance of Aluminum Alloy Modified by Laser Radiation
Authors: Mroczkowska K.M. , Antończak A.J. , Gąsiorek J.
Published: October 2019

This study presents an analysis of the impact of the oxide layers, prepared utilizing fiber laser radiation (1062 nm) in ambient air with different process parameters, on the corrosion resistance of EN 5754 aluminum alloy. Due to both high corrosion resistance and high fatigue strength, a 5754 alloy is used, among others, in the marine, aerospace, automotive, and chemical industries. Nevertheless, it corrodes in aggressive environments (with high chloride ions concentration). The controlled delivery of laser radiation energy in the oxygen environment allows the formation of the oxide layer on the surface of the material. We have determined that it significantly affects the resistance of these materials to corrosion. As a result of laser irradiation, changes in the chemical structure of the surface layer (chemical composition as well as surface development) can be observed. It may exert both a positive and a negative consequence on the corrosion resistance. The electrochemical corrosion tests (potentiodynamic polarization and electrochemical impedance spectroscopy EIS) have been carried out in an aggressive environment (3% NaCl). Moreover, microscopic examination, chemical tests, and roughness were also performed. The study revealed that appropriate control of the laser process can significantly increase the original corrosion resistance of the 5754 aluminum alloy.
Comparing Sentiment- and Behavioral-Based Leading Indexes for Industrial Production: When Does Each Fail?
Authors: Seip Knut Lehre , Yilmaz Yunus , Schröder Michael
Published: October 2019

We apply a relatively novel leading–lagging (LL) method to four leading and one lagging indexes for industrial production (IP) in Germany. We obtain three sets of results. First, we show that the sentiment-based ifo index performs best in predicting the general changes in IP (−0.596, range −1.0 to 1.0, −1.0 being best). The ZEW index is very close (−0.583). In third place comes, somewhat unexpectedly, the behavioral-based unemployment index (−0.564), and last comes order flow, OF (−0.186). Second, we applied the LL method to predefined recession and recovery time windows. The recessions were best predicted (−0.70), the recoveries worst (−0.32), and the overall prediction was intermediate (−0.48). Third, the method identifies time windows automatically, even for short time windows, where the leading indexes fail. All indexes scored low during time windows around 1997 and 2005. Both periods correspond to anomalous periods in the German economy. The 1997 period coincides with “the great moderation” in the US at the end of a minor depression in Germany. Around 2005, oil prices increased from $10 to $60 a barrel. There were few orders, and monetary supply was low. Our policy implications suggest that the ZEW index performs best (including recessions and recoveries), but unemployment and monetary supply should probably be given more weight in sentiment forecasting.
Connecting Status and Professional Learning: An Analysis of Midwives Career Using the Place© Model
Authors: Gillen Patricia
Published: October 2019

This paper seeks to deconstruct the place of midwives as professionals using the novel interdisciplinary lens of the Place Model—an innovative analytical device which originated in education and has been previously applied to both teachers and teacher educators. The Place Model allows us to map the metaphorical professional landscape of the midwife and to consider how and where midwives are located in the combined context of two senses of place: in the sociological sense of public esteem and also the humanistic geography tradition of place as a cumulative process of professional learning. A range of exemplars will bring this map to life uncovering both the dystopias and potentially utopian places in which midwives find their various professional places in the world. The Model can be used to help student midwives to consider and take charge of their learning and status trajectories within the profession.
Survey on Routing Protocols for Vehicular Ad Hoc Networks Based on Multimetrics
Authors: Tripp-Barba Carolina , Zaldívar-Colado Aníbal , Urquiza-Aguiar Luis , Aguilar-Calderón José Alfonso
Published: October 2019

In the last few years, many routing protocols have been proposed for vehicular ad hoc networks (VANETs) because of their specific characteristics. Protocols that use several metrics have been shown to be the most adequate to VANETs due to their effectiveness in dealing with dynamic environment changes due to vehicle mobility. Metrics such as distance, density, link stability, speed, and position were selected by the authors for the best proposal. Several surveys of routing proposals have been generated to categorize contributions and their application scenarios, but none of them focused on multimetric approaches. In this paper, we present a review of the routing protocols based on more than one metric to select the best route in a VANET. The main objective of this research was to present the contemporary most frequently used metrics in the different proposals and their application scenarios. This review helps in the selection protocols or the creation of metrics when a new protocol is designed.This survey of multimetric VANET routing protocols employed systematic literature-review (SLR) methodology in four well-knownown databases that allowed to analyze current state-of-the-art proposals. In addition, this paper provides a description of these multimetric routing protocols. Our findings indicate that distance and speed are the most popular and versatile metrics. Finally, we define some possible directions for future research related to the use of this class of protocols.