bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of a Predictive Model for Calculating Ascent Time to a Target Temperature
Authors: Moon Jin , Chung Min , Song Hayub , Lee Se-Young
Published: December 2016

The aim of this study was to develop an artificial neural network (ANN) prediction model for controlling building heating systems. This model was used to calculate the ascent time of indoor temperature from the setback period (when a building was not occupied) to a target setpoint temperature (when a building was occupied). The calculated ascent time was applied to determine the proper moment to start increasing the temperature from the setback temperature to reach the target temperature at an appropriate time. Three major steps were conducted: (1) model development; (2) model optimization; and (3) performance evaluation. Two software programs—Matrix Laboratory (MATLAB) and Transient Systems Simulation (TRNSYS)—were used for model development, performance tests, and numerical simulation methods. Correlation analysis between input variables and the output variable of the ANN model revealed that two input variables (current indoor air temperature and temperature difference from the target setpoint temperature), presented relatively strong relationships with the ascent time to the target setpoint temperature. These two variables were used as input neurons. Analyzing the difference between the simulated and predicted values from the ANN model provided the optimal number of hidden neurons (9), hidden layers (3), moment (0.9), and learning rate (0.9). At the study’s conclusion, the optimized model proved its prediction accuracy with acceptable errors.
A Fault-Tolerant Location Approach for Transient Voltage Disturbance Source Based on Information Fusion
Authors: Weng Guoqing , Huang Feiteng , Yan Jun , Yang Xiaodong , Zhang Youbing , He Haibo
Published: December 2016

This paper proposed a fault-tolerant approach based on information fusion (IF) to automatically locate the transient voltage disturbance source (TVDS) in smart distribution grids. We first defined three credibility factors that will influence the reliability of the direction-judgments at each power quality monitor (PQM). Then we proposed two rules of influence and a verification factor for the distributed generation (DG) integration. Based on the two sets of direction-judgment criteria, a novel decision-making method with fault tolerance based on the IF theory is proposed for automatic location of the TVDS. Three critical schemes, including credibility fusion, conflict weakening, and correction for DG integration, have been integrated in the proposed fusion method, followed by a reliability evaluation of the location results. The proposed approach was validated on the IEEE 13-node test feeder, and the TVDS location results demonstrated the effectiveness and fault tolerance of the IF based approach.
An Experimental Study of the Impact of Dynamic Electricity Pricing on Consumer Behavior: An Analysis for a Remote Island in Japan
Authors: Nguyen Thoa , Shimada Koji , Ochi Yuki , Matsumoto Takuya , Matsugi Hiroshi , Awata Takao
Published: December 2016

The aim of this research was to investigate how consumer behavior changes after application of dynamic electricity pricing and the persistence of those changes. Based on the investigation results, the authors also discuss the policy implications of demand management to shift consumption to days that have more solar radiation, while at the same time reducing overall consumption. The dynamic pricing experiment was implemented on Nushima Island, located in the center of Japan, with the participation of 50 households. The methodologies used in this study are panel analysis with random effects, and the difference in differences method. Several linear regression analyses are performed to predict hourly electricity usage from a number of explanatory variables, such as life-style factors, the frequency of access to the visualization website, control for weather factors (wind speed and temperatures), and other attributes of the households to predict the log of hourly electric energy consumption. The results show that dynamic pricing brought about 13.8% reduction of electric energy consumption in comparison with the pre-experiment period. Also, by applying a new experimental design approach, this study finds data supportive of habit formation by participants. Based on the findings, this research tries to develop a policy for sustainable energy conservation in remote islands.
A Hybrid Method for Generation of Typical Meteorological Years for Different Climates of China
Authors: Zang Haixiang , Wang Miaomiao , Huang Jing , Wei Zhinong , Sun Guoqiang
Published: December 2016

Since a representative dataset of the climatological features of a location is important for calculations relating to many fields, such as solar energy system, agriculture, meteorology and architecture, there is a need to investigate the methodology for generating a typical meteorological year (TMY). In this paper, a hybrid method with mixed treatment of selected results from the Danish method, the Festa-Ratto method, and the modified typical meteorological year method is proposed to determine typical meteorological years for 35 locations in six different climatic zones of China (Tropical Zone, Subtropical Zone, Warm Temperate Zone, Mid Temperate Zone, Cold Temperate Zone and Tibetan Plateau Zone). Measured weather data (air dry-bulb temperature, air relative humidity, wind speed, pressure, sunshine duration and global solar radiation), which cover the period of 1994–2015, are obtained and applied in the process of forming TMY. The TMY data and typical solar radiation data are investigated and analyzed in this study. It is found that the results of the hybrid method have better performance in terms of the long-term average measured data during the year than the other investigated methods. Moreover, the Gaussian process regression (GPR) model is recommended to forecast the monthly mean solar radiation using the last 22 years (1994–2015) of measured data.
Direct Measurement of Tree Height Provides Different Results on the Assessment of LiDAR Accuracy
Authors: Sibona Emanuele , Vitali Alessandro , Meloni Fabio , Caffo Lucia , Dotta Alberto , Lingua Emanuele , Motta Renzo , Garbarino Matteo
Published: December 2016

In this study, airborne laser scanning-based and traditional field-based survey methods for tree heights estimation are assessed by using one hundred felled trees as a reference dataset. Comparisons between remote sensing and field-based methods were applied to four circular permanent plots located in the western Italian Alps and established within the Alpine Space project NewFor. Remote sensing (Airborne Laser Scanning, ALS), traditional field-based (indirect measurement, IND), and direct measurement of felled trees (DIR) methods were compared by using summary statistics, linear regression models, and variation partitioning. Our results show that tree height estimates by Airborne Laser Scanning (ALS) approximated to real heights (DIR) of felled trees. Considering the species separately, Larix decidua was the species that showed the smaller mean absolute difference (0.95 m) between remote sensing (ALS) and direct field (DIR) data, followed by Picea abies and Pinus sylvestris (1.13 m and 1.04 m, respectively). Our results cannot be generalized to ALS surveys with low pulses density (<5/m2) and with view angles far from zero (nadir). We observed that the tree heights estimation by laser scanner is closer to actual tree heights (DIR) than traditional field-based survey, and this was particularly valid for tall trees with conical shape crowns.
Reynolds Stresses and Hemolysis in Turbulent Flow Examined by Threshold Analysis
Authors: Ozturk Mesude , O’Rear Edgar , Papavassiliou Dimitrios
Published: December 2016

Use of laminar flow-derived power law models to predict hemolysis with turbulence remains problematical. Flows in a Couette viscometer and a capillary tube have been simulated to investigate various combinations of Reynolds and/or viscous stresses power law models for hemolysis prediction. A finite volume-based computational method provided Reynolds and viscous stresses so that the effects of area-averaged and time-averaged Reynolds stresses, as well as total, viscous, and wall shear on hemolysis prediction could be assessed. The flow computations were conducted by using Reynolds-Averaged Navier-Stokes models of turbulence (k-ε and k-ω SST) to simulate four different experimental conditions in a capillary tube and seven experimental conditions in a Couette viscometer taken from the literature. Power law models were compared by calculating standard errors between measured hemolysis values and those derived from power law models with data from the simulations. In addition, suitability of Reynolds and viscous stresses was studied by threshold analysis. Results showed there was no evidence of a threshold value for hemolysis in terms of Reynolds and viscous stresses. Therefore, Reynolds and viscous stresses are not good predictors of hemolysis. Of power law models, the Zhang power law model (Artificial Organs, 2011, 35, 1180–1186) gives the lowest error overall for the hemolysis index and Reynolds stress (0.05570), while Giersiepen’s model (The International journal of Artificial Organs, 1990, 13, 300–306) yields the highest (6.6658), and intermediate errors are found through use of Heuser’s (Biorheology, 1980, 17, 17–24) model (0.3861) and Fraser’s (Journal of Biomechanical Engineering, 2012, 134, 081002) model (0.3947).
On Effective Degrees of Freedom in the Early Universe
Authors: Husdal Lars
Published: December 2016

We explore the effective degrees of freedom in the early Universe, from before the electroweak scale at a few femtoseconds after the Big Bang until the last positrons disappeared a few minutes later. We look at the established concepts of effective degrees of freedom for energy density, pressure, and entropy density, and introduce effective degrees of freedom for number density as well. We discuss what happens with particle species as their temperature cools down from relativistic to semi- and non-relativistic temperatures, and then annihilates completely. This will affect the pressure and the entropy per particle. We also look at the transition from a quark-gluon plasma to a hadron gas. Using a list a known hadrons, we use a “cross-over” temperature of 214 MeV, where the effective degrees of freedom for a quark-gluon plasma equals that of a hadron gas.
Conical Stream of the Two-Sided Jets in NGC 4261 over the Range of 103–109 Schwarzschild Radii
Authors: Nakahara Satomi , Doi Akihiro , Murata Yasuhiro , Hada Kazuhiro , Nakamura Masanori , Asada Keiichi
Published: December 2016

We report the jet width profile of of the nearby ( ∼ 30 Mpc ) AGN NGC 4261 for both the approaching jet and the counter jet at radial distances ranging from ∼ 10 3 – 10 9 Schwarzschild radius ( R S ) from the central engine. Our Very Large Array (VLA) and Very Long Baseline Array (VLBA) observations reveal that the jets maintain a conical structure on both sides over the range 10 3 – 10 9 R S without any structural transition (i.e., parabolic to conical) like in the approaching jet in M87. Thus, NGC 4261 will provide a unique opportunity to examine the conical jet hypothesis in blazars, while it may require some additional consideration on the acceleration and collimation process in AGN jets.
Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases
Authors: Song Chunzi , Sakurai Masayuki , Shiromoto Yusuke , Nishikura Kazuko
Published: December 2016

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1′s actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases.
Dysregulated MicroRNA Expression Profiles and Potential Cellular, Circulating and Polymorphic Biomarkers in Non-Hodgkin Lymphoma
Authors: Bradshaw Gabrielle , Sutherland Heidi , Haupt Larisa , Griffiths Lyn
Published: December 2016

A large number of studies have focused on identifying molecular biomarkers, including microRNAs (miRNAs) to aid in the diagnosis and prognosis of the most common subtypes of non-Hodgkin lymphoma (NHL), Diffuse Large B-cell Lymphoma and Follicular Lymphoma. NHL is difficult to diagnose and treat with many cases becoming resistant to chemotherapy, hence the need to identify improved biomarkers to aid in both diagnosis and treatment modalities. This review summarises more recent research on the dysregulated miRNA expression profiles found in NHL, as well as the regulatory role and biomarker potential of cellular and circulating miRNAs found in tissue and serum, respectively. In addition, the emerging field of research focusing on miRNA single nucleotide polymorphisms (miRSNPs) in genes of the miRNA biogenesis pathway, in miRNA genes themselves, and in their target sites may provide new insights on gene expression changes in these genes. These miRSNPs may impact miRNA networks and have been shown to play a role in a host of different cancer types including haematological malignancies. With respect to NHL, a number of SNPs in miRNA-binding sites in target genes have been shown to be associated with overall survival.
A Mineralized Alga and Acritarch Dominated Microbiota from the Tully Formation (Givetian) of Pennsylvania, USA
Authors: Chamberlain John , Chamberlain Rebecca , Brown James
Published: December 2016

Sphaeromorphic algal cysts, most probably of the prasinophyte Tasmanites, and acanthomorphic acritarch vesicles, most probably Solisphaeridium, occur in a single 20 cm thick bed of micritic limestone in the lower part of the Middle Devonian (Givetian) Tully Formation near Lock Haven, Pennsylvania. Specimens are composed of authigenic calcite and pyrite crystals about 5–10 µm in length. Some specimens are completely calcitic; some contain both pyrite and calcite; and many are composed totally of pyrite. The microfossils are about 80 to 150 µm in diameter. Many show signs of originally containing a flexible wall composed of at least two layers. Some appear to have been enclosed in a mucilaginous sheath or membrane when alive. The acanthomorphic forms have spines that are up to 20 µm in length, expand toward the base, and are circular in cross-section. The microflora occurs with microscopic molluscs, dacryoconarids, the enigmatic Jinonicella, and the oldest zooecia of ctenostome bryozoans known from North America. The microalgal horizon lacks macrofossils although small burrows are present. Microalgae and acritarchs have been preserved via a complex preservational process involving rapid, bacterially-mediated post-mortem mineralization of dead cells. The microfossil horizon, and possibly much of the Tully Formation at Lock Haven with similar lithology, formed in a relatively deep, off-shore basin with reduced oxygen availability in the substrate.
Special Issue Introduction “Transcultural Literary Studies: Politics, Theory, and Literary Analysis”
Authors: Fischer Bernd
Published: December 2016

As we witness the rise of intemperate nationalism, self-indulgent nativism, and aggressive xenophobia in many countries, multi- and intercultural studies and initiatives have come under considerable pressure.[...]
Impact of Time-Varying Treatment Exposures on the Risk of Venous Thromboembolism in Multiple Myeloma
Authors: Brown Joshua , Adams Val , Moga Daniela
Published: December 2016

Multiple myeloma (MM) has one of the highest risks of venous thromboembolism (VTE) of all cancers due to pathologic changes and treatment-related exposures. This study assessed the one-year incidence of VTE in newly diagnosed MM and to determine the baseline and time-varying treatment-related factors associated with VTE risk in a U.S.-based cohort. MM patients were identified and age, gender, and baseline comorbidities were determined. Treatment-related exposures included thalidomide derivatives (IMIDs), proteasome inhibitors, cytotoxic chemotherapy, steroids, erythropoietin-stimulating agents (ESAs), stem cell transplants (SCT), hospitalizations, infection, and central venous catheters (CVC). Multiple statistical models were used including a baseline competing risks model, a time-varying exposure Cox proportional hazard (CPH) model, and a case-time-control analysis. The overall incidence of VTE was 107.2 per 1000 person-years with one-half of the VTEs occurring in the first 90 days. The baseline model showed that increasing age, heart failure, and hypertension were associated with one-year incidence of VTE. MM-specific IMID treatment had lower than expected associations with VTE based on prior literature. Instead, exposure to ESAs, SCT, CVC, and infection had higher associations. Based on these results, VTE risk in MM may be less straightforward than considering only chemotherapy exposures, and other treatment-related exposures should be considered to determine patient risk.
Modeling Driver Behavior near Intersections in Hidden Markov Model
Authors: Li Juan , He Qinglian , Zhou Hang , Guan Yunlin , Dai Wei
Published: December 2016

Intersections are one of the major locations where safety is a big concern to drivers. Inappropriate driver behaviors in response to frequent changes when approaching intersections often lead to intersection-related crashes or collisions. Thus to better understand driver behaviors at intersections, especially in the dilemma zone, a Hidden Markov Model (HMM) is utilized in this study. With the discrete data processing, the observed dynamic data of vehicles are used for the inference of the Hidden Markov Model. The Baum-Welch (B-W) estimation algorithm is applied to calculate the vehicle state transition probability matrix and the observation probability matrix. When combined with the Forward algorithm, the most likely state of the driver can be obtained. Thus the model can be used to measure the stability and risk of driver behavior. It is found that drivers’ behaviors in the dilemma zone are of lower stability and higher risk compared with those in other regions around intersections. In addition to the B-W estimation algorithm, the Viterbi Algorithm is utilized to predict the potential dangers of vehicles. The results can be applied to driving assistance systems to warn drivers to avoid possible accidents.
Artificial Diets for Mosquitoes
Authors: Gonzales Kristina , Hansen Immo
Published: December 2016

Mosquito-borne diseases are responsible for more than a million human deaths every year. Modern mosquito control strategies such as sterile insect technique (SIT), release of insects carrying a dominant lethal (RIDL), population replacement strategies (PR), and Wolbachia-based strategies require the rearing of large numbers of mosquitoes in culture for continuous release over an extended period of time. Anautogenous mosquitoes require essential nutrients for egg production, which they obtain through the acquisition and digestion of a protein-rich blood meal. Therefore, mosquito mass production in laboratories and other facilities relies on vertebrate blood from live animal hosts. However, vertebrate blood is expensive to acquire and hard to store for longer times especially under field conditions. This review discusses older and recent studies that were aimed at the development of artificial diets for mosquitoes in order to replace vertebrate blood.
Empirical Analysis and Modeling of Stop-Line Crossing Time and Speed at Signalized Intersections
Authors: Tang Keshuang , Wang Fen , Yao Jiarong , Sun Jian
Published: December 2016

In China, a flashing green (FG) indication of 3 s followed by a yellow (Y) indication of 3 s is commonly applied to end the green phase at signalized intersections. Stop-line crossing behavior of drivers during such a phase transition period significantly influences safety performance of signalized intersections. The objective of this study is thus to empirically analyze and model drivers’ stop-line crossing time and speed in response to the specific phase transition period of FG and Y. High-resolution trajectories for 1465 vehicles were collected at three rural high-speed intersections with a speed limit of 80 km/h and two urban intersections with a speed limit of 50 km/h in Shanghai. With the vehicle trajectory data, statistical analyses were performed to look into the general characteristics of stop-line crossing time and speed at the two types of intersections. A multinomial logit model and a multiple linear regression model were then developed to predict the stop-line crossing patterns and speeds respectively. It was found that the percentage of stop-line crossings during the Y interval is remarkably higher and the stop-line crossing time is approximately 0.7 s longer at the urban intersections, as compared with the rural intersections. In addition, approaching speed and distance to the stop-line at the onset of FG as well as area type significantly affect the percentages of stop-line crossings during the FG and Y intervals. Vehicle type and stop-line crossing pattern were found to significantly influence the stop-line crossing speed, in addition to the above factors. The red-light-running seems to occur more frequently at the large intersections with a long cycle length.
Interest Aware Location-Based Recommender System Using Geo-Tagged Social Media
Authors: AlBanna Basma , Sakr Mahmoud , Moussa Sherin , Moawad Ibrahim
Published: December 2016

Advances in location acquisition and mobile technologies led to the addition of the location dimension to Social Networks (SNs) and to the emergence of a newer class called Location-Based Social Networks (LBSNs). While LBSNs are richer in their model and functions than SNs, they fail so far to attract as many users as SNs. On the other hand, SNs have large amounts of geo-tagged media that are under-utilized. In this paper, we propose an Interest-Aware Location-Based Recommender system (IALBR), which combines the advantages of both LBSNs and SNs, in order to provide interest-aware location-based recommendations. This recommender system is proposed as an extension to LBSNs. It is novel in: (1) utilizing the geo-content in both LBSNs and SNs; (2) ranking the recommendations based on a novel scoring method that maps to the user interests. It also works for passive users who are not active content contributors to the LBSN. This feature is critical to increase the number of LBSN users. Moreover, it helps with reducing the cold start problem, which is a common problem facing the new users of recommender systems who get random unsatisfying recommendations. This is due to the lack of user interest awareness, which is reliant on user history in most of the recommenders. We evaluated our system with a large-scale real dataset collected from foursquare with respect to precision, recall and the f-measure. We also compared the results with a ground truth system using metrics like the normalized discounted cumulative gain and the mean absolute error. The results confirm that the proposed IALBR generates more efficient recommendations than baselines in terms of interest awareness.
Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease
Authors: Kwakowsky Andrea , Milne Michael , Waldvogel Henry , Faull Richard
Published: December 2016

The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease.
A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis
Authors: Yang Lianjun , Wang Liping , Wang Xin , Xian Cory , Lu Hai
Published: December 2016

Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, for which the pathogenesis is thought to be a result of the combination of host genetic factors and environmental triggers. However, the precise factors that determine one’s susceptibility to AS remain to be unraveled. With 100 trillion bacteria residing in the mammalian gut having established a symbiotic relation with their host influencing many aspects of host metabolism, physiology, and immunity, a growing body of evidence suggests that intestinal microbiota may play an important role in AS. Several mechanisms have been suggested to explain the potential role of the microbiome in the etiology of AS, such as alterations of intestinal permeability, stimulation of immune responses, and molecular mimicry. In this review, the existing evidence for the involvement of the microbiome in AS pathogenesis was discussed and the potential of intestinal microbiome-targeting strategies in the prevention and treatment of AS was evaluated.
Metabolomic Approaches to Explore Chemical Diversity of Human Breast-Milk, Formula Milk and Bovine Milk
Authors: Qian Linxi , Zhao Aihua , Zhang Yinan , Chen Tianlu , Zeisel Steven , Jia Wei , Cai Wei
Published: December 2016

Although many studies have been conducted on the components present in human breast milk (HM), research on the differences of chemical metabolites between HM, bovine milk (BM) and formula milk (FM) is limited. This study was to explore the chemical diversity of HM, BM and FM by metabolomic approaches. GC-TOFMS and UPLC-QTOFMS were applied to investigate the metabolic compositions in 30 HM samples, 20 FM samples and 20 BM samples. Metabolite profiling identified that most of the non-esterified fatty acids, which reflected the hydrolysis of triglycerides, were much more abundant in HM than those in FM and BM, except for palmitic acid and stearic acid. The levels of tricarboxylic acid (TCA) intermediates were much higher in FM and BM than those in HM. Each type of milk also showed its unique composition of free amino acids and free carbohydrates. In conclusion, higher levels of non-esterified saturated fatty acids with aliphatic tails <16 carbons, monounsaturated fatty acids and polyunsaturated fatty acids and lower levels of TCA intermediates are characteristic of HM, as compared with FM and BM. The content of non-esterified fatty acids may reflect the hydrolysis of triglycerides in different milk types.
Identification of Heat Shock Transcription Factor Genes Involved in Thermotolerance of Octoploid Cultivated Strawberry
Authors: Liao Wan-Yu , Lin Lee-Fong , Jheng Jing-Lian , Wang Chun-Chung , Yang Jui-Hung , Chou Ming-Lun
Published: December 2016

Heat shock transcription factors (HSFs) are mainly involved in the activation of genes in response to heat stress as well as other abiotic and biotic stresses. The growth, development, reproduction, and yield of strawberry are strongly limited by extreme temperatures and droughts. In this study, we used Illumina sequencing and obtained transcriptome data set from Fragaria × ananassa Duchessne cv. Toyonoka. Six contigs and three unigenes were confirmed to encode HSF proteins (FaTHSFs). Subsequently, we characterized the biological functions of two particularly selected unigenes, FaTHSFA2a and FaTHSFB1a, which were classified into class A2 and B HSFs, respectively. Expression assays revealed that FaTHSFA2a and FaTHSFB1a expression was induced by heat shock and correlated well with elevated ambient temperatures. Overexpression of FaTHSFA2a and FaTHSFB1a resulted in the activation of their downstream stress-associated genes, and notably enhanced the thermotolerance of transgenic Arabidopsis plants. Besides, both FaTHSFA2a and FaTHSFB1a fusion proteins localized in the nucleus, indicating their similar subcellular distributions as transcription factors. Our yeast one-hybrid assay suggested that FaTHSFA2a has trans-activation activity, whereas FaTHSFB1a expresses trans-repression function. Altogether, our annotated transcriptome sequences provide a beneficial resource for identifying most genes expressed in octoploid strawberry. Furthermore, HSF studies revealed the possible insights into the molecular mechanisms of thermotolerance, thus rendering valuable molecular breeding to improve the tolerance of strawberry in response to high-temperature stress.
Modulation of GLO1 Expression Affects Malignant Properties of Cells
Authors: Hutschenreuther Antje , Bigl Marina , Hemdan Nasr , Debebe Tewodros , Gaunitz Frank , Birkenmeier Gerd
Published: December 2016

The energy metabolism of most tumor cells relies on aerobic glycolysis (Warburg effect) characterized by an increased glycolytic flux that is accompanied by the increased formation of the cytotoxic metabolite methylglyoxal (MGO). Consequently, the rate of detoxification of this reactive glycolytic byproduct needs to be increased in order to prevent deleterious effects to the cells. This is brought about by an increased expression of glyoxalase 1 (GLO1) that is the rate-limiting enzyme of the MGO-detoxifying glyoxalase system. Here, we overexpressed GLO1 in HEK 293 cells and silenced it in MCF-7 cells using shRNA. Tumor-related properties of wild type and transformed cells were compared and key glycolytic enzyme activities assessed. Furthermore, the cells were subjected to hypoxic conditions to analyze the impact on cell proliferation and enzyme activities. Our results demonstrate that knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas no functional alterations where found by overexpression of GLO1 in HEK 293 cells. In contrast, hypoxia caused inhibition of cell growth of all cells except of those overexpressing GLO1. Altogether, we conclude that GLO1 on one hand is crucial to maintaining tumor characteristics of malignant cells, and, on the other hand, supports malignant transformation of cells in a hypoxic environment when overexpressed.
Recent Methods for Purification and Structure Determination of Oligonucleotides
Authors: Zhang Qiulong , Lv Huanhuan , Wang Lili , Chen Man , Li Fangfei , Liang Chao , Yu Yuanyuan , Jiang Feng , Lu Aiping , Zhang Ge
Published: December 2016

Aptamers are single-stranded DNA or RNA oligonucleotides that can interact with target molecules through specific three-dimensional structures. The excellent features, such as high specificity and affinity for target proteins, small size, chemical stability, low immunogenicity, facile chemical synthesis, versatility in structural design and engineering, and accessible for site-specific modifications with functional moieties, make aptamers attractive molecules in the fields of clinical diagnostics and biopharmaceutical therapeutics. However, difficulties in purification and structural identification of aptamers remain a major impediment to their broad clinical application. In this mini-review, we present the recently attractive developments regarding the purification and identification of aptamers. We also discuss the advantages, limitations, and prospects for the major methods applied in purifying and identifying aptamers, which could facilitate the application of aptamers.
Review of Toxic Epidermal Necrolysis
Authors: Harris Victoria , Jackson Christopher , Cooper Alan
Published: December 2016

Toxic epidermal necrolysis (TEN) is a rare but life threatening mucocutaneous reaction to drugs or their metabolites. It is characterised by widespread keratinocyte apoptosis and sloughing of the skin, erosions of the mucous membranes, painful blistering, and severe systemic disturbance. The pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA)-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand. Currently, granulysin is accepted as the most important mediator of T cell proliferation. There is uncertainty around the accepted management of TEN. The lack of definitive management guidelines for TEN is explained in part by the rarity of the disease and its high mortality rate, which makes it difficult to conduct randomised control trials on emerging therapies. Developments have been made in pharmacogenomics, with numerous HLA alleles identified; however, these have largely been ethnically specific. These associations have translated into screening recommendations for Han Chinese.
Neurotoxicity of a Biopesticide Analog on Zebrafish Larvae at Nanomolar Concentrations
Authors: Nasri Ahmed , Valverde Audrey , Roche Daniel , Desrumaux Catherine , Clair Philippe , Beyrem Hamouda , Chaloin Laurent , Ghysen Alain , Perrier Véronique
Published: December 2016

Despite the ever-increasing role of pesticides in modern agriculture, their deleterious effects are still underexplored. Here we examine the effect of A6, a pesticide derived from the naturally-occurring α-terthienyl, and structurally related to the endocrine disrupting pesticides anilinopyrimidines, on living zebrafish larvae. We show that both A6 and an anilinopyrimidine, cyprodinyl, decrease larval survival and affect central neurons at micromolar concentrations. Focusing on a superficial and easily observable sensory system, the lateral line system, we found that defects in axonal and sensory cell regeneration can be observed at much lower doses, in the nanomolar range. We also show that A6 accumulates preferentially in lateral line neurons and hair cells. We examined whether A6 affects the expression of putative target genes, and found that genes involved in apoptosis/cell proliferation are down-regulated, as well as genes reflecting estrogen receptor activation, consistent with previous reports that anilinopyrimidines act as endocrine disruptors. On the other hand, canonical targets of endocrine signaling are not affected, suggesting that the neurotoxic effect of A6 may be due to the binding of this compound to a recently identified, neuron-specific estrogen receptor.
Alterations of Epigenetic Regulators in Pancreatic Cancer and Their Clinical Implications
Authors: Silverman Brittany , Shi Jiaqi
Published: December 2016

Pancreatic cancer is one of the most aggressive human cancer types with a five-year survival less than 7%. Emerging evidence revealed that many genetic alterations in pancreatic cancer target epigenetic regulators. Some of these mutations are driver mutations in cancer development. Several most important mechanisms of epigenetic regulations include DNA methylation, histone modifications (methylation, acetylation, and ubiquitination), chromatin remodeling, and non-coding ribonucleic acids (RNAs). These modifications can alter chromatin structure and promoter accessibility, and thus lead to aberrant gene expression. However, exactly how these alterations affect epigenetic reprogramming in pancreatic cancer cells and in different stages of tumor development is still not clear. This mini-review summarizes the current knowledge of epigenetic alterations in pancreatic cancer development and progression, and discusses the clinical applications of epigenetic regulators as diagnostic biomarkers and therapeutic targets in pancreatic cancer.
Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism
Authors: Zhang Weiying , Kang Min , Zhang Tingting , Li Bo , Liao Xueyin , Wang Rensheng
Published: December 2016

Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-κB p65, Bcl-2 and VEGF proteins without affecting other NF-κB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-κB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC.
Moringa oleifera Seeds and Oil: Characteristics and Uses for Human Health
Authors: Leone Alessandro , Spada Alberto , Battezzati Alberto , Schiraldi Alberto , Aristil Junior , Bertoli Simona
Published: December 2016

Moringa oleifera seeds are a promising resource for food and non-food applications, due to their content of monounsaturated fatty acids with a high monounsaturated/saturated fatty acids (MUFA/SFA) ratio, sterols and tocopherols, as well as proteins rich in sulfated amino acids. The rapid growth of Moringa trees in subtropical and tropical areas, even under conditions of prolonged drought, makes this plant a reliable resource to enhance the nutritional status of local populations and, if rationalized cultivation practices are exploited, their economy, given that a biodiesel fuel could be produced from a source not in competition with human food crops. Despite the relatively diffuse use of Moringa seeds and their oil in traditional medicine, no pharmacological activity study has been conducted on humans. Some encouraging evidence, however, justifies new efforts to obtain clear and definitive information on the benefits to human health arising from seed consumption. A critical review of literature data concerning the composition of Moringa oil has set in motion a plan for future investigations. Such investigations, using the seeds and oil, will focus on cultivation conditions to improve plant production, and will study the health effects on human consumers of Moringa seeds and their oil.
Tumour Heterogeneity: The Key Advantages of Single-Cell Analysis
Authors: Tellez-Gabriel Marta , Ory Benjamin , Lamoureux Francois , Heymann Marie-Francoise , Heymann Dominique
Published: December 2016

Tumour heterogeneity refers to the fact that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity), and it is caused by genetic and non-genetic factors. The heterogeneity of cancer cells introduces significant challenges in using molecular prognostic markers as well as for classifying patients that might benefit from specific therapies. Thus, research efforts for characterizing heterogeneity would be useful for a better understanding of the causes and progression of disease. It has been suggested that the study of heterogeneity within Circulating Tumour Cells (CTCs) could also reflect the full spectrum of mutations of the disease more accurately than a single biopsy of a primary or metastatic tumour. In previous years, many high throughput methodologies have raised for the study of heterogeneity at different levels (i.e., RNA, DNA, protein and epigenetic events). The aim of the current review is to stress clinical implications of tumour heterogeneity, as well as current available methodologies for their study, paying specific attention to those able to assess heterogeneity at the single cell level.
A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA
Authors: Esposito Maria , Nunziato Marcella , Starnone Flavio , Telese Antonella , Calabrese Alessandra , D’Aiuto Giuseppe , Pucci Pietro , D’Aiuto Massimiliano , Baralle Francisco , D’Argenio Valeria , Salvatore Francesco
Published: December 2016

About 10% of all breast cancers arise from hereditary mutations that increase the risk of breast and ovarian cancers; and about 25% of these are associated with the BRCA1 or BRCA2 genes. The identification of BRCA1/BRCA2 mutations can enable physicians to better tailor the clinical management of patients; and to initiate preventive measures in healthy carriers. The pathophysiological significance of newly identified variants poses challenges for genetic counseling. We characterized a new BRCA1 variant discovered in a breast cancer patient during BRCA1/2 screening by next-generation sequencing. Bioinformatic predictions; indicating that the variant is probably pathogenetic; were verified using retro-transcription of the patient’s RNA followed by PCR amplifications performed on the resulting cDNA. The variant causes the loss of a canonic donor splice site at position +2 in BRCA1 intron 21; and consequently the partial retention of 156 bp of intron 21 in the patient’s transcript; which demonstrates that this novel BRCA1 mutation plays a pathogenetic role in breast cancer. These findings enabled us to initiate appropriate counseling and to tailor the clinical management of this family. Lastly; these data reinforce the importance of studying the effects of sequence variants at the RNA level to verify their potential role in disease onset.
Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis
Authors: Charlier Edith , Relic Biserka , Deroyer Céline , Malaise Olivier , Neuville Sophie , Collée Julie , Malaise Michel , De Seny Dominique
Published: December 2016

Osteoarthritis (OA) is a joint pathology characterized by progressive cartilage degradation. Medical care is mainly based on alleviating pain symptoms. Compelling studies report the presence of empty lacunae and hypocellularity in cartilage with aging and OA progression, suggesting that chondrocyte cell death occurs and participates to OA development. However, the relative contribution of apoptosis per se in OA pathogenesis appears complex to evaluate. Indeed, depending on technical approaches, OA stages, cartilage layers, animal models, as well as in vivo or in vitro experiments, the percentage of apoptosis and cell death types can vary. Apoptosis, chondroptosis, necrosis, and autophagic cell death are described in this review. The question of cell death causality in OA progression is also addressed, as well as the molecular pathways leading to cell death in response to the following inducers: Fas, Interleukin-1β (IL-1β), Tumor Necrosis factor-α (TNF-α), leptin, nitric oxide (NO) donors, and mechanical stresses. Furthermore, the protective role of autophagy in chondrocytes is highlighted, as well as its decline during OA progression, enhancing chondrocyte cell death; the transition being mainly controlled by HIF-1α/HIF-2α imbalance. Finally, we have considered whether interfering in chondrocyte apoptosis or promoting autophagy could constitute therapeutic strategies to impede OA progression.
Genetic Analysis of Human Chymotrypsin-Like Elastases 3A and 3B (CELA3A and CELA3B) to Assess the Role of Complex Formation between Proelastases and Procarboxypeptidases in Chronic Pancreatitis
Authors: Párniczky Andrea , Hegyi Eszter , Tóth Anna , Szücs Ákos , Szentesi Andrea , Vincze Áron , Izbéki Ferenc , Németh Balázs , Hegyi Péter , Sahin-Tóth Miklós
Published: December 2016

Human chymotrypsin-like elastases 3A and 3B (CELA3A and CELA3B) are the products of gene duplication and share 92% identity in their primary structure. CELA3B forms stable complexes with procarboxypeptidases A1 and A2 whereas CELA3A binds poorly due to the evolutionary substitution of Ala241 with Gly in exon 7. Since position 241 is polymorphic both in CELA3A (p.G241A) and CELA3B (p.A241G), genetic analysis can directly assess whether individual variability in complex formation might alter risk for chronic pancreatitis. Here we sequenced exon 7 of CELA3A and CELA3B in a cohort of 225 subjects with chronic pancreatitis (120 alcoholic and 105 non-alcoholic) and 300 controls of Hungarian origin. Allele frequencies were 2.5% for CELA3A p.G241A and 1.5% for CELA3B p.A241G in controls, and no significant difference was observed in patients. Additionally, we identified six synonymous variants, two missense variants, a gene conversion event and ten variants in the flanking intronic regions. Variant c.643-7G>T in CELA3B showed an association with alcoholic chronic pancreatitis with a small protective effect (OR = 0.59, 95% CI = 0.39–0.89, p = 0.01). Functional analysis of missense variants revealed no major defects in secretion or activity. We conclude that variants affecting amino-acid position 241 in CELA3A and CELA3B are not associated with chronic pancreatitis, indicating that changes in complex formation between proelastases and procarboxypeptidases do not alter pancreatitis risk.