bluuebunny/crossref_metadata_2025 huggingface dataset:
An LSTM-Based Deep Learning Approach for Classifying Malicious Traffic at the Packet Level
Authors: Hwang Ren-Hung , Peng Min-Chun , Nguyen Van-Linh , Chang Yu-Lun
Published: August 2019

Recently, deep learning has been successfully applied to network security assessments and intrusion detection systems (IDSs) with various breakthroughs such as using Convolutional Neural Networks (CNN) and Long Short-Term Memory (LSTM) to classify malicious traffic. However, these state-of-the-art systems also face tremendous challenges to satisfy real-time analysis requirements due to the major delay of the flow-based data preprocessing, i.e., requiring time for accumulating the packets into particular flows and then extracting features. If detecting malicious traffic can be done at the packet level, detecting time will be significantly reduced, which makes the online real-time malicious traffic detection based on deep learning technologies become very promising. With the goal of accelerating the whole detection process by considering a packet level classification, which has not been studied in the literature, in this research, we propose a novel approach in building the malicious classification system with the primary support of word embedding and the LSTM model. Specifically, we propose a novel word embedding mechanism to extract packet semantic meanings and adopt LSTM to learn the temporal relation among fields in the packet header and for further classifying whether an incoming packet is normal or a part of malicious traffic. The evaluation results on ISCX2012, USTC-TFC2016, IoT dataset from Robert Gordon University and IoT dataset collected on our Mirai Botnet show that our approach is competitive to the prior literature which detects malicious traffic at the flow level. While the network traffic is booming year by year, our first attempt can inspire the research community to exploit the advantages of deep learning to build effective IDSs without suffering significant detection delay.
Aerodynamic and Structural Characteristics of a Centrifugal Compressor Impeller
Authors: Jebieshia T R , Raman Senthil Kumar , Kim Heuy Dong
Published: August 2019

The present study focuses on the aerodynamic performance and structural analysis of the centrifugal compressor impeller. The performance characteristics of the impeller are analyzed with and without splitter blades by varying the total number of main and splitter blades. The operating conditions of the compressor under centrifugal force and pressure load from the aerodynamic analysis are applied to the impeller blade and hub to perform the one-way Fluid–Structure Interaction (FSI). For the stress assessment, maximum equivalent von Mises stresses in the impeller blades are compared with the maximum allowable stress of the impeller material. The effects of varying the pressure field on the deformation and stress of the impeller are also calculated. The aerodynamic and structural performance of the centrifugal compressor at 73,000 rpm are investigated in terms of the efficiency, pressure ratio, equivalent von Mises stress, and total deformation of the impeller.
Optimal Charging of Plug-In Electric Vehicle: Considering Travel Behavior Uncertainties and Battery Degradation
Authors: Tayarani Hanif , Jahangir Hamidreza , Nadafianshahamabadi Razieh , Aliakbar Golkar Masoud , Ahmadian Ali , Elkamel Ali
Published: August 2019

The negative environmental impacts of using fossil fuel-powered vehicles underlined the need for inventing an alternative eco-friendly transportation fleet. Plug-in electrical vehicles (PEVs) are introduced to cut the continuing increase in energy use and carbon emission of the urban mobility. However, the increased demand for mobility, and therefore energy, can create constraints on the power network which can reduce the benefits of electrification as a certain and reliable source. Thus, the rise in the use of electric vehicles needs electric grids to be able to feed the increased energy demand while the current infrastructure supports it. In this paper, we introduce a methodological framework for scheduling smart PEVs charging by considering the uncertainties and battery degradation. This framework includes an economic model for charging and discharging of PEVs which has been implemented in a 21-node sample distribution network with a wind turbine as a distributed generation (DG) unit. Our proposed approach indicates that the optimal charging of the PEVs has a high impact on the distribution network operation, particularly under the high market penetration of PEVs. Thus, the smart grid to vehicle (G2V) charging mode is a potential solution to maximize the PEV’s owner profit, while considering the battery degradation cost of the PEVs. The simulation result indicates that smart charging effectuation is economical.
Circular Economy and E-Waste: An Opportunity from RFID TAGs
Authors: Condemi Alessia , Cucchiella Federica , Schettini Domenico
Published: August 2019

In this work, a deep economic and technical analysis for the enhancement of e-waste hierarchy applied to the Radio Frequency Identification (RFID) tags is presented. Nowadays, the RFID technology represents a valuable solution for many applications to improve the quality and efficiency of the supply chain, as well as for enhanced people or object identification and smart devices. This leads to massive usage of such devices that could represent a threat to the environment, since they are often considered as generic waste and no specific e-waste policy has been identified for RFID. For these reasons, the paper presents a study based on the desk research technique to propose several possibilities currently available for producers of different RFID devices in order to mitigate this problem at every e-waste hierarchy stage, i.e., ecological design and prevention, reuse, recycle, and disposal. Moreover, a cost/benefit analysis has been reported in order to highlight the economic advantages related to the RFID tags reuse, as well as environmental impact reduction. Results proved that passive RFID tags represent the major candidate for the e-waste hierarchy enhancement at every level, demonstrating that it is more convenient for the producer to consider an ecologically aware design and promote a take-back system for tags in order to take advantages from the solution proposed for the RFID e-waste hierarchy.
Passive Sampling as a Low-Cost Method for Monitoring Air Pollutants in the Baikal Region (Eastern Siberia)
Authors: Khuriganova Olga I. , Obolkin Vladimir A. , Golobokova Liudmila P. , Bukin Yuri S. , Khodzher Tamara V.
Published: August 2019

The measured concentrations of inorganic pollutants, such as ozone (2015–2018), sulfur, and nitrogen oxides (2012–2018) at air monitoring sites in the south of Eastern Siberia were sampled, following the passive sampling method, and analyzed. The spatial inhomogeneity of atmospheric gas concentrations is presented. The ozone concentration is lower in urban areas than those in rural areas and the background level. However, the nitrogen and sulfur oxide concentrations are higher in the atmosphere over the city site. The seasonal dependence of the ozone concentration was determined using its maximum (March–April) and minimum (September–October) levels. The dynamics of the nitrogen and sulfur oxide concentrations indicate that they are at their highest in December–June and their lowest in July–August. To verify the validity of the pollutant concentration measurements sampled by passive sampling, we compared our results with those obtained following the automatic and filter pack methods. A linear regression analysis and a pairwise modification of Student’s t test evaluated the concentrations of the air pollutant, sampled and measured using different methods, and they correlate well (r = 0.7–0.9). Full validation of the passive sampling method is not possible for some sites; therefore it is necessary to remove the remaining systematic errors in future work.
The Role of Synoptic Cyclones for the Formation of Arctic Summer Circulation Patterns as Clustered by Self-Organizing Maps
Authors: Lee Min-Hee , Kim Joo-Hong
Published: August 2019

Contribution of extra-tropical synoptic cyclones to the formation of mean summer atmospheric circulation patterns in the Arctic domain (≥60° N) was investigated by clustering dominant Arctic circulation patterns based on daily mean sea-level pressure using self-organizing maps (SOMs). Three SOM patterns were identified; one pattern had prevalent low-pressure anomalies in the Arctic Circle (SOM1), while two exhibited opposite dipoles with primary high-pressure anomalies covering the Arctic Ocean (SOM2 and SOM3). The time series of their occurrence frequencies demonstrated the largest inter-annual variation in SOM1, a slight decreasing trend in SOM2, and the abrupt upswing after 2007 in SOM3. Analyses of synoptic cyclone activity using the cyclone track data confirmed the vital contribution of synoptic cyclones to the formation of large-scale patterns. Arctic cyclone activity was enhanced in the SOM1, which was consistent with the meridional temperature gradient increases over the land–Arctic ocean boundaries co-located with major cyclone pathways. The composite daily synoptic evolution of each SOM revealed that all three SOMs persisted for less than five days on average. These evolutionary short-term weather patterns have substantial variability at inter-annual and longer timescales. Therefore, the synoptic-scale activity is central to forming the seasonal-mean climate of the Arctic.
Brewing and Craft Beer
Authors: Guido Luis F.
Published: August 2019

Beer is a beverage with more than 8000 years of history, and the process of brewing has not changed much over the centuries [...]
Inactivation of Aldehyde Dehydrogenase by Disulfiram in the Presence and Absence of Lipoic Acid or Dihydrolipoic Acid: An in Vitro Study
Authors: Bilska-Wilkosz Anna , Górny Magdalena , Iciek Małgorzata
Published: August 2019

The inhibition of aldehyde dehydrogenase (ALDH) by disulfiram (DSF) in vitro can be prevented and/or reversed by dithiothreitol (DTT), which is a well-known low molecular weight non-physiological redox reagent commonly used in laboratory experiments. These observations inspired us to ask the question whether the inhibition of ALDH by DSF can be preserved or abolished also by dihydrolipoic acid (DHLA), which is the only currently known low molecular weight physiological dithiol in the body of humans and other animals. It can even be metaphorized that DHLA is an “endogenous DTT”. Lipoic acid (LA) is the oxidized form of DHLA. We investigated the inactivation of ALDH derived from yeast and rat liver by DSF in the presence or absence of LA or DHLA. The results clearly show that DHLA is able both to restore and protect ALDH activity blocked by DSF. The proposed mechanism is discussed.
The Protective Effect of Hispidin against Hydrogen Peroxide-Induced Oxidative Stress in ARPE-19 Cells via Nrf2 Signaling Pathway
Authors: Huang Sung-Ying , Chang Shu-Fang , Chau Siu-Fung , Chiu Sheng-Chun
Published: August 2019

Hispidin, a polyphenol compound isolated from Phellinus linteus, has been reported to possess antioxidant activities. In this study, we aimed to investigate the mechanisms underlying the protective effect of hispidin against hydrogen peroxide (H2O2)-induced oxidative stress on Adult Retinal Pigment Epithelial cell line-19 (ARPE-19) cells. Hispidin was not cytotoxic to ARPE-19 cells at concentrations of less than 50 μM. The levels of intracellular reactive oxygen species (ROS) were analyzed by dichlorofluorescin diacetate (DCFDA) staining. Hispidin significantly restored H2O2-induced cell death and reduced the levels of intracellular ROS. The expression levels of antioxidant enzymes, such as NAD(P)H:Quinine oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) were examined using real-time PCR and Western blotting. Our results showed that hispidin markedly enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, NQO-1, GCLM, and GCLC in a dose-dependent manner. Furthermore, knockdown experiments revealed that transfection with Nrf2 siRNA successfully suppresses the hispidin activated Nrf2 signaling in ARPE-19 cells. Moreover, activation of the c-Jun N-terminal kinase (JNK) pathway is involved in mediating the protective effects of hispidin on the ARPE-19 cells. Thus, the present study demonstrated that hispidin provides protection against H2O2-induced damage in ARPE-19 cells via activation of Nrf2 signaling and up-regulation of its downstream targets, including Phase II enzymes, which might be associated with the activation of the JNK pathway.
Towards Mechanism-Based Treatments for Fragile X Syndrome
Authors: Kumari Daman , Gazy Inbal
Published: August 2019

Fragile X syndrome (FXS) is the most common heritable form of intellectual disability, as well as the most common known monogenic cause of autism spectrum disorder (ASD), affecting 1 in 4000–8000 people worldwide [...]
Pro-Nerve Growth Factor Induces Activation of RhoA Kinase and Neuronal Cell Death
Authors: Sycheva Marina , Sustarich Jake , Zhang Yuxian , Selvaraju Vaithinathan , Geetha Thangiah , Gearing Marla , Babu Jeganathan Ramesh
Published: August 2019

We have previously shown that the expression of pro-nerve growth factor (proNGF) was significantly increased, nerve growth factor (NGF) level was decreased, and the expression of p75NTR was enhanced in Alzheimer’s disease (AD) hippocampal samples. NGF regulates cell survival and differentiation by binding TrkA and p75NTR receptors. ProNGF is the precursor form of NGF, binds to p75NTR, and induces cell apoptosis. The objective of this study is to determine whether the increased p75NTR expression in AD is due to the accumulation of proNGF and Rho kinase activation. PC12 cells were stimulated with either proNGF or NGF. Pull-down assay was carried out to determine the RhoA kinase activity. We found the expression of p75NTR was enhanced by proNGF compared to NGF. The proNGF stimulation also increased the RhoA kinase activity leading to apoptosis. The expression of active RhoA kinase was found to be increased in human AD hippocampus compared to control. The addition of RhoA kinase inhibitor Y27632 not only blocked the RhoA kinase activity but also reduced the expression of p75NTR receptor and inhibited the activation of JNK and MAPK induced by proNGF. This suggests that overexpression of proNGF in AD enhances p75NTR expression and activation of RhoA, leading to neuronal cell death.
How Therapeutic Tapping Can Alter Neural Correlates of Emotional Prosody Processing in Anxiety
Authors: König Nicola , Steber Sarah , Seebacher Josef , von Prittwitz Quinten , Bliem Harald R. , Rossi Sonja
Published: August 2019

Anxiety disorders are the most common psychological disorders worldwide resulting in a great demand of adequate and cost-effective treatment. New short-term interventions can be used as an effective adjunct or alternative to pharmaco- and psychotherapy. One of these approaches is therapeutic tapping. It combines somatic stimulation of acupressure points with elements from Cognitive Behavioral Therapy (CBT). Tapping reduces anxiety symptoms after only one session. Anxiety is associated with a deficient emotion regulation for threatening stimuli. These deficits are compensated e.g., by CBT. Whether Tapping can also elicit similar modulations and which dynamic neural correlates are affected was subject to this study. Anxiety patients were assessed listening to pseudowords with a different emotional prosody (happy, angry, fearful, and neutral) prior and after one Tapping session. The emotion-related component Late Positive Potential (LPP) was investigated via electroencephalography. Progressive Muscle Relaxation (PMR) served as control intervention. Results showed LPP reductions for negative stimuli after the interventions. Interestingly, PMR influenced fearful and Tapping altered angry prosody. While PMR generally reduced arousal for fearful prosody, Tapping specifically affected fear-eliciting, angry stimuli, and might thus be able to reduce anxiety symptoms. Findings highlight the efficacy of Tapping and its impact on neural correlates of emotion regulation.
Impacts of Microclimate Conditions on the Energy Performance of Buildings in Urban Areas
Authors: Javanroodi Kavan , Nik Vahid M.
Published: August 2019

Urbanization trends have changed the morphology of cities in the past decades. Complex urban areas with wide variations in built density, layout typology, and architectural form have resulted in more complicated microclimate conditions. Microclimate conditions affect the energy performance of buildings and bioclimatic design strategies as well as a high number of engineering applications. However, commercial energy simulation engines that utilize widely-available mesoscale weather data tend to underestimate these impacts. These weather files, which represent typical weather conditions at a location, are mostly based on long-term metrological observations and fail to consider extreme conditions in their calculation. This paper aims to evaluate the impacts of hourly microclimate data in typical and extreme climate conditions on the energy performance of an office building in two different urban areas. Results showed that the urban morphology can reduce the wind speed by 27% and amplify air temperature by more than 14%. Using microclimate data, the calculated outside surface temperature, operating temperature and total energy demand of buildings were notably different to those obtained using typical regional climate model (RCM)–climate data or available weather files (Typical Meteorological Year or TMY), i.e., by 61%, 7%, and 21%, respectively. The difference in the hourly peak demand during extreme weather conditions was around 13%. The impact of urban density and the final height of buildings on the results are discussed at the end of the paper.
Targeting Oncogenic BRAF: Past, Present, and Future
Authors: Zaman Aubhishek , Wu Wei , Bivona Trever G.
Published: August 2019

Identifying recurrent somatic genetic alterations of, and dependency on, the kinase BRAF has enabled a “precision medicine” paradigm to diagnose and treat BRAF-driven tumors. Although targeted kinase inhibitors against BRAF are effective in a subset of mutant BRAF tumors, resistance to the therapy inevitably emerges. In this review, we discuss BRAF biology, both in wild-type and mutant settings. We discuss the predominant BRAF mutations and we outline therapeutic strategies to block mutant BRAF and cancer growth. We highlight common mechanistic themes that underpin different classes of resistance mechanisms against BRAF-targeted therapies and discuss tumor heterogeneity and co-occurring molecular alterations as a potential source of therapy resistance. We outline promising therapy approaches to overcome these barriers to the long-term control of BRAF-driven tumors and emphasize how an extensive understanding of these themes can offer more pre-emptive, improved therapeutic strategies.
Baseline Genomic Features in BRAFV600-Mutated Metastatic Melanoma Patients Treated with BRAF Inhibitor + MEK Inhibitor in Routine Care
Authors: Louveau Baptiste , Jouenne Fanelie , Reger de Moura Coralie , Sadoux Aurelie , Baroudjian Barouyr , Delyon Julie , Herms Florian , De Masson Adele , Da Meda Laetitia , Battistella Maxime , Dumaz Nicolas , Lebbe Celeste , Mourah Samia
Published: August 2019

In BRAFV600mut metastatic melanoma, the combination of BRAF and MEK inhibitors (BRAFi, MEKi) has undergone multiple resistance mechanisms, limiting its clinical benefit and resulting in the need for response predicting biomarkers. Based on phase III clinical trial data, several studies have previously explored baseline genomic features associated with response to BRAFi + MEKi. Using a targeted approach that combines the examination of mRNA expression and DNA alterations in a subset of genes, we performed an analysis of baseline genomic alterations involved in MAPK inhibitors’ resistance in a real-life cohort of BRAFV600mut metastatic melanoma patients. Twenty-seven patients were included in this retrospective study, and tumor samples were analyzed when the BRAFi + MEKi therapy was initiated. The clinical characteristics of our cohort were consistent with previously published studies. The BRAFi + MEKi treatment was initiated in seven patients as a following-line treatment, and had a specific transcriptomic profile exhibiting 14 genes with lower mRNA expression. However, DNA alterations in CCND1, RB1, and MET were only observed in patients who received BRAFi + MEKi as the first-line treatment. Furthermore, KIT mRNA expression was significantly higher in patients showing clinical benefit from the combined therapy, emphasizing the tumor-suppressor role of KIT already described within the context of BRAF-mutant melanoma.
Neuromuscular Junction as an Entity of Nerve-Muscle Communication
Authors: Lepore Elisa , Casola Irene , Dobrowolny Gabriella , Musarò Antonio
Published: August 2019

One of the crucial systems severely affected in several neuromuscular diseases is the loss of effective connection between muscle and nerve, leading to a pathological non-communication between the two tissues. The neuromuscular junction (NMJ) represents the critical region at the level of which muscle and nerve communicate. Defects in signal transmission between terminal nerve endings and muscle membrane is a common feature of several physio-pathologic conditions including aging and Amyotrophic Lateral Sclerosis (ALS). Nevertheless, controversy exists on whether pathological events beginning at the NMJ precede or follow loss of motor units. In this review, the role of NMJ in the physio-pathologic interplay between muscle and nerve is discussed.
Genetic Variation Underpinning ADHD Risk in a Caribbean Community
Authors: Puentes-Rozo Pedro J. , Acosta-López Johan E. , Cervantes-Henríquez Martha L. , Martínez-Banfi Martha L. , Mejia-Segura Elsy , Sánchez-Rojas Manuel , Anaya-Romero Marco E. , Acosta-Hoyos Antonio , García-Llinás Guisselle A. , Mastronardi Claudio A. , Pineda David A. , Castellanos F. Xavier , Arcos-Burgos Mauricio , Vélez Jorge I.
Published: August 2019

Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele; p = 2.46 × 10−4), rs2282794-FGF1 (A allele; p = 1.33 × 10−2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10−2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.
Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis
Authors: Das Manjusri , Deb Moonmoon , Laha Dipranjan , Joseph Matthew , Kanji Suman , Aggarwal Reeva , Iwenofu O. Hans , Pompili Vincent J. , Jarjour Wael , Das Hiranmoy
Published: August 2019

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic differentiation, matrix metalloproteinases (MMPs), and inflammatory cytokines in K/BxN serum-induced mice. The severities of RA pathogenesis, as well as the causative and resultant cellular and molecular factors, were further confirmed in monocyte-specific KLF2 deficient mice. In addition, induction of RA resulted in a decreased level of KLF2 in monocytes isolated from both mice and humans along with higher migration of activated monocytes to the RA sites in humans. Mechanistically, overexpression of KLF2 decreased the level of MMP9; conversely, knockdown of KLF2 increased MMP9 in monocytes along with enrichment of active histone marks and histone acetyltransferases on the MMP9 promoter region. These findings define the critical regulatory role of myeloid KLF2 in RA pathogenesis.
Keeping the Centromere under Control: A Promising Role for DNA Methylation
Authors: Scelfo Andrea , Fachinetti Daniele
Published: August 2019

In order to maintain cell and organism homeostasis, the genetic material has to be faithfully and equally inherited through cell divisions while preserving its integrity. Centromeres play an essential task in this process; they are special sites on chromosomes where kinetochores form on repetitive DNA sequences to enable accurate chromosome segregation. Recent evidence suggests that centromeric DNA sequences, and epigenetic regulation of centromeres, have important roles in centromere physiology. In particular, DNA methylation is abundant at the centromere, and aberrant DNA methylation, observed in certain tumors, has been correlated to aneuploidy and genomic instability. In this review, we evaluate past and current insights on the relationship between centromere function and the DNA methylation pattern of its underlying sequences.
Absence of Uncoupling Protein-3 at Thermoneutrality Impacts Lipid Handling and Energy Homeostasis in Mice
Authors: Lombardi Assunta , Busiello Rosa Anna , De Matteis Rita , Lionetti Lillà , Savarese Sabrina , Moreno Maria , Gentile Alessandra , Silvestri Elena , Senese Rosalba , de Lange Pieter , Cioffi Federica , Lanni Antonia , Goglia Fernando
Published: August 2019

The role of uncoupling protein-3 (UCP3) in energy and lipid metabolism was investigated. Male wild-type (WT) and UCP3-null (KO) mice that were housed at thermoneutrality (30 °C) were used as the animal model. In KO mice, the ability of skeletal muscle mitochondria to oxidize fatty acids (but not pyruvate or succinate) was reduced. At whole animal level, adult KO mice presented blunted resting metabolic rates, energy expenditure, food intake, and the use of lipids as metabolic substrates. When WT and KO mice were fed with a standard/low-fat diet for 80 days, since weaning, they showed similar weight gain and body composition. Interestingly, KO mice showed lower fat accumulation in visceral adipose tissue and higher ectopic fat accumulation in liver and skeletal muscle. When fed with a high-fat diet for 80 days, since weaning, KO mice showed enhanced energy efficiency and an increased lipid gain (thus leading to a change in body composition between the two genotypes). We conclude that UCP3 plays a role in energy and lipid homeostasis and in preserving lean tissues by lipotoxicity, in mice that were housed at thermoneutrality.
Biomimetic In Vitro Model of Cell Infiltration into Skin Scaffolds for Pre-Screening and Testing of Biomaterial-Based Therapies
Authors: Ballesteros-Cillero Rafael , Davison-Kotler Evan , Kohli Nupur , Marshall William S. , García-Gareta Elena
Published: August 2019

Due to great clinical need, research where different biomaterials are tested as 3D scaffolds for skin tissue engineering has increased. In vitro studies use a cell suspension that is simply pipetted onto the material and cultured until the cells migrate and proliferate within the 3D scaffold, which does not mimic the in vivo reality. Our aim was to engineer a novel biomimetic in vitro model that mimics the natural cell infiltration process occurring in wound healing, thus offering a realistic approach when pre-screening and testing new skin substitutes. Our model consists of porous membrane cell culture inserts coated with gelatin and seeded with human dermal fibroblasts, inside which two different commercially available dermal substitutes were placed. Several features relevant to the wound healing process (matrix contraction, cell infiltration and proliferation, integration of the biomaterial with the surrounding tissue, and secretion of exogenous cytokines and growth factors) were evaluated. Our results showed that cells spontaneously infiltrate the materials and that our engineered model is able to induce and detect subtle differences between different biomaterials. The model allows for room for improvements or “adds-on” and miniaturization and can contribute to the development of functional and efficient skin substitutes for burns and chronic wounds.
The Snapdragon LATE ELONGATED HYPOCOTYL Plays A Dual Role in Activating Floral Growth and Scent Emission
Authors: Terry Marta I. , Pérez-Sanz Fernando , Navarro Pedro J. , Weiss Julia , Egea-Cortines Marcos
Published: August 2019

The plant circadian clock controls a large number of internal processes, including growth and metabolism. Scent emission displays a circadian pattern in many species such as the snapdragon. Here we show that knocking down LATE ELONGATED HYPOCOTYL in Antirrhinum majus affects growth and scent emission. In order to gain an understanding of the growth kinetics, we took a phenomic approach using in-house artificial vision systems, obtaining time-lapse videos. Wild type flowers showed a higher growth speed than knockdown plants. The maximal growth rate was decreased by 22% in plants with lower LHY expression. Floral volatiles were differentially affected as RNAi plants showed advanced emission of compounds synthesized from cinnamic acid and delayed emission of metabolites of benzoic acid. The monoterpenes myrcene and ocimene were delayed, whereas the sesquiterpene farnesene was advanced. Overall, transgenic lines showed an altered volatile emission pattern and displayed a modified scent profile. Our results show that AmLHY plays an important role in the quantitative and qualitative control of floral growth and scent emission.
mTOR-Dependent Stimulation of IL20RA Orchestrates Immune Cell Trafficking through Lymphatic Endothelium in Patients with Crohn’s Disease
Authors: Ungaro Federica , Garlatti Valentina , Massimino Luca , Spinelli Antonino , Carvello Michele , Sacchi Matteo , Spanò Salvatore , Colasante Gaia , Valassina Nicholas , Vetrano Stefania , Malesci Alberto , Peyrin-Biroulet Laurent , Danese Silvio , D’Alessio Silvia
Published: August 2019

Crohn’s disease (CD) is a chronic inflammatory condition that can affect different portions of the gastrointestinal tract. Lymphatic drainage was demonstrated to be dysfunctional in CD pathogenesis, ultimately causing the failure of the resolution of intestinal inflammation. To investigate the molecular mechanisms underlying these dysfunctions, we isolated human intestinal lymphatic endothelial cells (HILECs) from surgical specimens of patients undergoing resection for complicated CD (CD HILEC) and from a disease-free margin of surgical specimens of patients undergoing resection for cancer (healthy HILEC). Both cell types underwent transcriptomic profiling, and their barrier functionality was tested using a transwell-based co-culture system between HILEC and lamina propria mononuclear cells (LPMCs). Results showed CD HILEC displayed a peculiar transcriptomic signature that highlighted mTOR signaling as an orchestrator of leukocyte trafficking through the lymphatic barrier of CD patients. Moreover, we demonstrated that LPMC transmigration through the lymphatic endothelium of patients with CD depends on the capability of mTOR to trigger interleukin 20 receptor subunit α (IL20RA)-mediated intracellular signaling. Conclusively, our study suggests that leukocyte trafficking through the intestinal lymphatic microvasculature can be controlled by modulating IL20RA, thus leading to the resolution of chronic inflammation in patients with CD.
17β-Estradiol Modulates SIRT1 and Halts Oxidative Stress-Mediated Cognitive Impairment in a Male Aging Mouse Model
Authors: Khan Mehtab , Ullah Rahat , Rehman Shafiq Ur , Shah Shahid Ali , Saeed Kamran , Muhammad Tahir , Park Hyun Young , Jo Myeung Hoon , Choe Kyonghwan , Rutten Bart P.F. , Ok Kim Myeong
Published: August 2019

Oxidative stress has been considered the main mediator in neurodegenerative disease and in normal aging processes. Several studies have reported that the accumulation of reactive oxygen species (ROS), elevated oxidative stress, and neuroinflammation result in cellular malfunction. These conditions lead to neuronal cell death in aging-related neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease. Chronic administration of d-galactose (d-gal) for a period of 10 weeks causes ROS generation and neuroinflammation, ultimately leading to cognitive impairment. In this study, we evaluated the estrogen receptor α (ERα)/silent mating type information regulation 2 homolog 1 (SIRT1)-dependent antioxidant efficacy of 17β-estradiol against d-gal-induced oxidative damage-mediated cognitive dysfunction in a male mouse model. The results indicate that 17β-estradiol, by stimulating ERα/SIRT1, halts d-gal-induced oxidative stress–mediated JNK/NF-ҡB overexpression, neuroinflammation and neuronal apoptosis. Moreover, 17β-estradiol ameliorated d-gal-induced AD-like pathophysiology, synaptic dysfunction and memory impairment in adult mouse brains. Interestingly, inhibition of SIRT1 with Ex527 (a potent and selective SIRT1 inhibitor) further enhanced d-gal-induced toxicity and abolished the beneficial effect of 17β-estradiol. Most importantly, for the first time, our molecular docking study reveals that 17β-estradiol allosterically increases the expression of SIRT1 and abolishes the inhibitory potential of d-ga. In summary, we can conclude that 17β-estradiol, in an ERα/SIRT1-dependent manner, abrogates d-gal-induced oxidative stress–mediated memory impairment, neuroinflammation, and neurodegeneration in adult mice.
Extracellular Juxtamembrane Motif Critical for TrkB Preformed Dimer and Activation
Authors: Shen Jianying , Sun Dang , Shao Jingyu , Chen Yanbo , Pang Keliang , Guo Wei , Lu Bai
Published: August 2019

Receptor tyrosine kinases are believed to be activated through ligand-induced dimerization. We now demonstrate that in cultured neurons, a substantial amount of endogenous TrkB, the receptor for brain-derived neurotrophic factor (BDNF), exists as an inactive preformed dimer, and the application of BDNF activates the pre-existing dimer. Deletion of the extracellular juxtamembrane motif (EJM) of TrkB increased the amount of preformed dimer, suggesting an inhibitory role of EJM on dimer formation. Further, binding of an agonistic antibody (MM12) specific to human TrkB-EJM activated the full-length TrkB and unexpectedly also truncated TrkB lacking ECD (TrkBdelECD365), suggesting that TrkB is activated by attenuating the inhibitory effect of EJM through MM12 binding-induced conformational changes. Finally, in cells co-expressing rat and human TrkB, MM12 could only activate TrkB human-human dimer but not TrkB human-rat TrkB dimer, indicating that MM12 binding to two TrkB monomers is required for activation. Our results support a model that TrkB preforms as an inactive dimer and BDNF induces TrkB conformation changes leading to its activation.
Design of Scorodite@Fe3O4 Core–Shell Materials and the Fe3O4 Shell Prevents Leaching of Arsenic from Scorodite in Neutral and Alkaline Environments
Authors: Wang Yang , Rong Zhihao , Tang Xincun , Cao Shan
Published: August 2019

In recent years, arsenic pollution has seriously harmed human health. Arsenic-containing waste should be treated to render it harmless and immobilized to form a stable, solid material. Scorodite (iron arsenate) is recognized as the best solid arsenic material in the world. It has the advantages of high arsenic content, good stability, and a low iron/arsenic molar ratio. However, scorodite can decompose and release arsenic in a neutral and alkaline environment. Ferroferric oxide (Fe3O4) is a common iron oxide that is insoluble in acid and alkali solutions. Coating a Fe3O4 shell that is acid- and alkali-resistant on the surface of scorodite crystals will improve the stability of the material. In this study, a scorodite@Fe3O4 core–shell structure material was synthesized. The synthesized core–shell material was detected by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Raman, and energy-dispersive X-ray spectroscopy (EDS) techniques, and the composition and structure were confirmed. The synthesis condition and forming process were analyzed. Long-term leaching tests were conducted to evaluate the stability of the synthesized scorodite@Fe3O4. The results indicate that the scorodite@Fe3O4 had excellent stability after 20 days of exposure to neutral and weakly alkaline solutions. The inert Fe3O4 shell could prevent the scorodite core from corrosion by the external solution. The scorodite@Fe3O4 core–shell structure material was suitable for the immobilization of arsenic and has potential application prospects for the treatment of arsenic-containing waste.
Effect of the Variable Viscosity on the Peristaltic Flow of Newtonian Fluid Coated with Magnetic Field: Application of Adomian Decomposition Method for Endoscope
Authors: Akram Safia , H. Aly Emad , Afzal Farkhanda , Nadeem Sohail
Published: August 2019

In the present analysis, peristaltic flow was discussed for MHD Newtonian fluid through the gap between two coaxial tubes, where the viscosity of the fluid is treated as variable. In addition, the inner tube was considered to be at rest, while the outer tube had the sinusoidal wave traveling down its motion. Further, the assumptions of long wave length and low Reynolds number were taken into account for the formulation of the problem. A closed form solution is presented for general viscosity using the Adomian decomposition method. Numerical illustrations that show the physical effects and pertinent features were investigated for different physical included phenomenon. It was found that the pressure rise increases with an increase in Hartmann number, and frictional forces for the outer and inner tube decrease with an increase in Hartmann number when the viscosity is constant. It was also observed that the size of the trapping bolus decreases with an increase in Hartmann number, and increases with an increase in amplitude ratio when the viscosity is parameter.
The Influence of B, N and Si Doping on the CH3 Adsorption on the Diamond Surface Based on DFT Calculations
Authors: Wang Liang , Liu Jiangshan , Tang Tang
Published: August 2019

To better understand the influence mechanism of boron, nitrogen and silicon dopants on the growth of chemical vapor deposition (CVD) diamond film, density functional calculations have been performed to reveal the different impact of the impurities on the CH3 adsorption on diamond surface. The substituted doping and radical doping of diamond (111) and (100) − 2 × 1 surface are both considered. The calculation results indicate that the CH3 radicals are hardly adsorbed on nitrogen atoms and thus may cause vacancy in the diamond lattice easily. Boron substituted doping will disfavor the adsorption of CH3 due to the lacking of valence electron. However, the empty p orbitals of boron atom will help the chemical adsorbing of CH3 radicals. The substituted silicon doping has little influence on the CH3 adsorption, as Si atom has the same outer valence electron structure with C atom. In the case of radical doping, the adsorption energy of CH3 will be reduced due to the steric hindrance between NH2 or SiH3 with CH3. The adsorption energy can be slightly enhanced when BH2 radical is pre-adsorbed on diamond (111) surface. However, the BH2 pre-adsorbed on diamond (100) − 2 × 1 surface may interact with surface radical carbon site and result in a large reduction of CH3 adsorption energy. Thus, the boron doping may hinder the formation of the (100) facet during the CVD diamond deposition under a certain condition.
Simulation-Based System-Level Conducted Susceptibility Testing Method and Application to the Evaluation of Conducted-Noise Filters
Authors: Joo Junho , Kwak Sang Il , Kwon Jong Hwa , Song Eakhwan
Published: August 2019

In this paper, a simulation-based system-level conducted susceptibility (CS) testing method for a wireless power transfer (WPT) system is proposed. The proposed method employs 3-dimensional electromagnetic (3D EM) models as well as equivalent circuit models to replace the measurement-based CS testing method based on the International Electrotechnical Commission 61000-4-6 standard. The conducted-noise source and equipment under test (EUT) are modeled in a circuit simulator. The conduction path, bulk current injection probe, and calibration jig are modeled using the 3D field simulator. A simple WPT system is designed and fabricated as the EUT for the CS test. The proposed method is successfully verified by comparing the voltage waveforms with measurement-based CS testing method. Additionally, as an application of the proposed method, a simulation-based evaluation of the conducted-noise filters is conducted. By using the proposed method, it is expected that the time and cost expense of setting up the test setup, as well as the testing procedure for the conventional measurement-based CS testing, will be drastically reduced. In addition, the proposed method can be used to estimate the conducted immunity of a system in the early stage of the design cycle prior to production.
Bark Beetle Epidemics, Life Satisfaction, and Economic Well-Being
Authors: Holmes Thomas , Koch Frank
Published: August 2019

Evidence of increased biotic disturbances in forests due to climate change is accumulating, necessitating the development of new approaches for understanding the impacts of natural disturbances on human well-being. The recent Mountain Pine Beetle (MPB) outbreak in the western United States, which was historically unprecedented in scale, provides an opportunity for testing the adequacy of the life satisfaction approach (LSA) to estimate the impact of large-scale forest mortality on subjective well-being. Prior research in this region used the hedonic method (HM) to estimate the economic impacts of the MPB outbreak, and results are used here to evaluate the reasonableness of economic estimates based upon the LSA. While economic estimates based upon the LSA model do not appear to be unreasonable, several limitations in using the LSA for nonmarket valuations are discussed. New avenues for research that link the LSA with stated preference methods are discussed that appear likely to address major concerns with standard LSA models as used in nonmarket valuation.
Identification of RING-H2 Gene Candidates Related to Wood Formation in Poplar
Authors: Tong Guimin , Shen Hongmei , Cao Shenquan , Xu Wenjing , Ma Xujun , Cheng Yuxiang
Published: August 2019

RING-H2 genes, the most abundant RING-type genes encoding putative ubiquitin ligase E3, are involved in diverse biological processes. Whether RING-H2 genes are related to wood formation remains to be identified in trees. In this study, we identified 288 RING-H2 genes in Populus trichocarpa, and found that the segmental and tandem duplication events contributed to RING-H2 gene expansion. Microarray dataset (from Affymetrix poplar genome arrays) showed that 64 of the 249 RING-H2 genes were highly or preferentially expressed in stem xylem. According to the AspWood RNAseq dataset, the transcription levels of genes PtrRHH21, 33, 48, 69, 88, 93, 94, 121, 141, 166, 175, 192, 208, 214, 250 and 257 were significantly increased in the xylem ranging from the expanding xylem to the lignifying xylem, suggesting their association with wood formation. Promoter analyses revealed that most of the preferentially xylem-expressed RING-H2 genes possessed SNBE, TERE, M46RE, AC and SMRE cis-elements, which are involved in secondary cell wall biosynthesis and programmed cell death. Based on the promoter GUS-based analysis result, PtrRHH94 was indicated to be associated with wood formation in transgenic P. trichocarpa. Taken together, dozens of Populus RING-H2 gene candidates associated with wood formation have been identified based on multiple gene expression analyses.
Dynamics of Abies nephrolepis Seedlings in Relation to Environmental Factors in Seorak Mountain, South Korea
Authors: Kim JiDong , Lim Jong-Hwan , Yun ChungWeon
Published: August 2019

We present novel evidence of environmental drivers of seedling density in Abies nephrolepis, an alpine and subalpine tree species. Continuous monitoring of natural conditions is required to understand forest ecosystem dynamics. We investigated Abies nephrolepis seedling dynamics in relation to biotic and abiotic factors. The survey, which included the measurement of trees and seedlings, was carried out from March to October in 2016 and 2018. Monitoring sites in the coniferous forests of Seorak Mountain were divided into 27 quadrats. We analyzed relationships using simple and multiple linear regression. The majority of Abies nephrolepis individuals had a diameter at breast height less than l0 cm, and the number of seedlings increased over the study period. This reflects survival and growth due to successive annual mast seeding events. Aspect direction (R2 = 0.201, p < 0.05), rock exposure (R2 = 0.364, p < 0.001), canopy openness (R2 = 0.322, p < 0.05), herbaceous cover (R2 = 0.268, p < 0.01), and basal area (R2 = 0.199, p < 0.05) show significant linear relationships with seedling density. Seedling density was positively related to rock exposure, canopy openness, and species richness, and there was a negative relationship between herbaceous cover and basal area (p < 0.0001). The relative importance of predictor variables was as follows: Rock exposure (40.3%), canopy openness (30.2%), basal area (13.9%), herbaceous cover (11.5%), and species richness (4.1%). Seedling density was most strongly influenced by the presence of large rocks, which provide shelter from harsh winds and a substrate for moss. We conclude that appropriate canopy openness creates a synergistic relationship. We found a positive association between the Abies nephrolepis seedling density in subalpine forests and certain physical environmental factors. Therefore, environmental gradients about the roles of rocks and canopies apply, even in this habitat.
Socioeconomic Impacts of the Billion Trees Afforestation Program in Khyber Pakhtunkhwa Province (KPK), Pakistan
Authors: Khan Naveed , Shah Syed Jamal , Rauf Tariq , Zada Muhammad , Yukun Cao , Harbi Jun
Published: August 2019

In recent decades, the terrestrial ecosystem in Khyber Pakhtunkhwa Province (KPK), Pakistan, has undergone tremendous destruction. To restore environmental conditions, the government implemented the Billion Tree Afforestation Program (BTAP), with a high target to impact multidimensional aspects of the terrestrial ecosystem. The government claims that it is local residents who have benefited the most from the BTAP. Hence, the objective of this research was to examine the socioeconomic impact and local rural perception of the BTAP in three districts of KPK. Primary data were collected from 406 households. Fundamental orientation theory was used to assess the social impacts of the BTAP, while cost–benefit analysis was applied to examine its economic impact. The results show that the overall social impacts of the BTAP are satisfactory and beneficial, increasing social sustainability by 69% between 2014 and 2018. Additionally, based on the cost–benefit analysis and perception-based analysis, it was found that the BTAP positively affects the economic conditions of rural households. The community livelihood increased during the program, with a total net income of 6.9 million USD in the three districts of KPK. It is concluded that the majority of respondents have benefited from participation in the BTAP. The sustainability of rural livelihood is one of the main concerns related to the establishment of the BTAP. Effort is needed by the government and other parties to both increase rural household income and to protect the environment.