bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Feasibility of Using the Bacteriophage T4 Lysozyme to Improve the Hydrolysis and Biochemical Methane Potential of Secondary Sludge
Authors: Kim Sangmin , Woo Seung-Gyun , Lee Joonyeob , Lee Dae-Hee , Hwang Seokhwan
Published: September 2019

Anaerobic digestion (AD) of secondary sludge is a rate-limiting step due to the bacterial cell wall. In this study, experiments were performed to characterize secondary sludges from three wastewater treatment plants (WWTPs), and to investigate the feasibility of using bacteriophage lysozymes to speed up AD by accelerating the degradation of bacterial cell walls. Protein was the main organic material (67.7% of volatile solids in the sludge). The bacteriophage T4 lysozyme (T4L) was tested for hydrolysis and biochemical methane potential. Variations in the volatile suspended solid (VSS) concentration and biogas production were monitored. The VSS reduction efficiencies by hydrolysis using T4L for 72 h increased and ranged from 17.8% to 26.4%. Biogas production using T4L treated sludges increased and biogas production was increased by as much as 82.4%. Biogas production rate also increased, and the average reaction rate coefficient of first-order kinetics was 0.56 ± 0.02/d, which was up to 47.5% higher compared to the untreated samples at the maximum. Alphaproteobacteria, Betaproteobacteria, Flavobacteriia, Gammaproteobacteria, and Sphingobacteriia were major microbial classes in all sludges. The interpretation of the microbial community structure indicated that T4L treatment is likely to increase the rate of cell wall digestion.
Effect of Saturated Steam Carried Downward on the Flow Properties in the Downcomer of Steam Generator
Authors: Liu Yan , Shi Hui-lie , Gui Chun , Wang Xian-yuan , Tian Rui-feng
Published: September 2019

The saturated water separated by the steam separator in a natural circulation steam generator may carry a small amount of saturated steam into the downcomer. The steam contacts subcooled water and condenses directly in the downcomer causing the variations in the pressure and steam quality and likely affecting the stability of the water cycle in the secondary loop. It is not conducive to core heat extraction and thus affects nuclear safety. The mathematical model of the downcomer was established in this study based on the internal structures of a natural circulation steam generator. The volume-of-fluid (VOF) and large-eddy-simulation (LES) models were used for analysis on FLUENT software (ANSYS, Pittsburgh, PA. USA) platform. The influence of direct contact condensation of top-down flowing steam on the flow properties in the downcomer of the steam generator under high pressure was studied. The trend of the temperature, pressure, and the void fraction were obtained by combining these models with the condensation model. Further, a one-dimensional calculation program based on the differential drop was also developed to assess the flow field in the downcomer. The calculation results are in good agreement with the experimental results which indicated that, when affected by the saturated steam carried downward, the flow temperature close to the exit of the downcomer rises slightly due to the absorption of the heat released by the steam condensation. Furthermore, the density corrected by the pressure-drop is more reliable than that corrected by the temperature. After the velocity in the downcomer has increased to a certain value, the sensitivity of steam quality to the subcooling degree in the downcomer begins to decline. The results in this paper can be used to perform stability analyses and to design steam generators. The results of research are helpful to the stability analysis and the design of a steam generator, and to improve the accuracy of the measurement of the steam generator operating parameters, thus enhancing the safety of Pressurize Water Reactor operating system.
Correction: Ducey et al. Differences in Microbial Communities and Pathogen Survival Between a Covered and Uncovered Anaerobic Lagoon. Environments, 2019, 6, 91
Authors: Ducey Thomas F. , Rashash Diana M. C. , Szogi Ariel A.
Published: September 2019

The authors would like to correct the published article [...]
Variation in the Canadian Fire Weather Index Thresholds for Increasingly Larger Fires in Portugal
Authors: Fernandes Paulo
Published: September 2019

Forest fire management relies on fire danger rating to optimize its suite of activities. Limiting fire size is the fire management target whenever minimizing burned area is the primary goal, such as in the Mediterranean Basin. Within the region, wildfire incidence is especially acute in Portugal, a country where fire-influencing anthropogenic and landscape features vary markedly within a relatively small area. This study establishes daily fire weather thresholds associated to transitions to increasingly larger fires for individual Portuguese regions (2001–2011 period), using the national wildfire and Canadian fire weather index (FWI) databases and logistic regression. FWI thresholds variation in relation to population density, topography, land cover, and net primary production (NPP) metrics is examined through regression and cluster analysis. Larger fires occur under increasingly higher fire danger. Resistance to fire spread (the fire-size FWI thresholds) varies regionally following biophysical gradients, and decreases under more complex topography and when NPP and occupation by flammable forest or by shrubland increase. Three main clusters synthesize these relationships and roughly coincide with the western north-central, eastern north-central and southern parts of the country. Quantification of fire-weather relationships can be improved through additional variables and analysis at other spatial scales.
Determination of Xanthohumol in Hops, Food Supplements and Beers by HPLC
Authors: Vázquez Loureiro Patricia , Hernández Jiménez Ignacio , Sendón Raquel , Rodriguez-Bernaldo de Quirós Ana , Barbosa-Pereira Letricia
Published: September 2019

Xanthohumol (XN) is the main prenylated chalcone present in hops (Humulus lupulus) with high biological activity, and it is of great importance for human health because of its antioxidant, anti-inflammatory, immunosuppressive and chemopreventive properties. This polyphenol can be included in the diet through foods in which hops are used, such as beer or food supplements. Because of their health benefits and the increasing interest of using hops as a novel nutraceutical, the aim of this work was the identification and quantification of XN in different types of samples using a method based on high resolution liquid chromatography with a diode array detector (HPLC–DAD). The method was validated in terms of linearity, limits of detection (LOD) and quantification (LOQ), repeatability and recovery. Acceptable linearity (r2 0.9999), adequate recovery (>90% in the most of cases) and good sensitivity (LOD 16 µg/L) were obtained. Furthermore, the presence of XN in all samples was confirmed using liquid chromatography coupled to mass spectrometry (LC-MS/MS) operated in negative ESI (electrospray system ionization) mode. The concentrations of XN determined in hop flowers and food supplements were above the LOQ, in a range between 0.106 and 12.7 mg/g. Beer may also represent an important source of dietary prenylflavonoids, with between 0.028 and 0.062 mg/L of XN. The results showed that the methodology proposed was suitable for the determination of XN in the different types of samples studied, and the amounts of XN varied significantly according to the selected product.
Status of Insecticide Resistance and Its Mechanisms in Anopheles gambiae and Anopheles coluzzii Populations from Forest Settings in South Cameroon
Authors: Bamou Roland , Sonhafouo-Chiana Nadège , Mavridis Konstantinos , Tchuinkam Timoléon , Wondji Charles S. , Vontas John , Antonio-Nkondjio Christophe
Published: September 2019

A key factor affecting malaria vector control efforts in Cameroon is the rapid expansion of insecticide resistance in Anopheles gambiae s.l (An. gambiae) populations; however, mechanisms involved in insecticide resistance in forest mosquito populations are still not well documented yet. The present study was conducted to screen molecular mechanisms conferring insecticide resistance in An. gambiae s.l. populations from the South Cameroon forest region. WHO bioassays were conducted with F0 An. gambiae females aged three to four days from forest (Sangmelima, Nyabessan, and Mbandjock) and urban sites (Yaoundé (Bastos and Nkolondom)), against pyrethroids (permethrin 0.75% and deltamethrin 0.05%) and carbamates (bendiocarb 0.1%). Members of the An. Gambiae s.l. species complex were identified using molecular diagnostic tools. TaqMan assays were used to screen for target site mutations. The expression profiles of eight genes implicated in insecticide resistance were assessed using RT-qPCR. Cuticle hydrocarbon lipids were measured to assess their potential implication in insecticide resistance. Both An. Gambiae and An. coluzzii were detected. An. gambiae was highly prevalent in Sangmelima, Nyabessan, Mbandjock, and Nkolondom. An. coluzzii was the only species found in the Yaoundé city center (Bastos). Low mortality rate to both pyrethroids and bendiocarb was recorded in all sites. High frequency of L1014F allele (75.32–95.82%) and low frequencies of L1014S (1.71–23.05%) and N1575Y (5.28–12.87%) were recorded. The G119S mutation (14.22–35.5%) was detected for the first time in An. gambiae populations from Cameroon. This mutation was rather absent from An. coluzzii populations. The detoxification genes Cyp6m2, Cyp9k1, Cyp6p4, Cyp6z1, as well as Cyp4g16 which catalyzes epicuticular hydrocarbon biosynthesis, were found to be overexpressed in at least one population. The total cuticular hydrocarvbon content, a proxy of cuticular resistance, did not show a pattern associated with pyrethroid resistance in these populations. The rapid emergence of multiple resistance mechanisms in An. Gambiae s.l. population from the South Cameroon forest region is of big concern and could deeply affect the sustainability of insecticide-based interventions strategies in this region.
Comparison between the Transcriptomes of ‘KDML105’ Rice and a Salt-Tolerant Chromosome Segment Substitution Line
Authors: Khrueasan Nopphawitchayaphong , Chutimanukul Panita , Plaimas Kitiporn , Buaboocha Teerapong , Siangliw Meechai , Toojinda Theerayut , Comai Luca , Chadchawan Supachitra
Published: September 2019

‘KDML105’ rice, known as jasmine rice, is grown in northeast Thailand. The soil there has high salinity, which leads to low productivity. Chromosome substitution lines (CSSLs) with the ‘KDML105’ rice genetic background were evaluated for salt tolerance. CSSL18 showed the highest salt tolerance among the four lines tested. Based on a comparison between the CSSL18 and ‘KDML105’ transcriptomes, more than 27,000 genes were mapped onto the rice genome. Gene ontology enrichment of the significantly differentially expressed genes (DEGs) revealed that different mechanisms were involved in the salt stress responses between these lines. Biological process and molecular function enrichment analysis of the DEGs from both lines revealed differences in the two-component signal transduction system, involving LOC_Os04g23890, which encodes phototropin 2 (PHOT2), and LOC_Os07g44330, which encodes pyruvate dehydrogenase kinase (PDK), the enzyme that inhibits pyruvate dehydrogenase in respiration. OsPHOT2 expression was maintained in CSSL18 under salt stress, whereas it was significantly decreased in ‘KDML105’, suggesting OsPHOT2 signaling may be involved in salt tolerance in CSSL18. PDK expression was induced only in ‘KDML105’. These results suggested respiration was more inhibited in ‘KDML105’ than in CSSL18, and this may contribute to the higher salt susceptibility of ‘KDML105’ rice. Moreover, the DEGs between ‘KDML105’ and CSSL18 revealed the enrichment in transcription factors and signaling proteins located on salt-tolerant quantitative trait loci (QTLs) on chromosome 1. Two of them, OsIRO2 and OsMSR2, showed the potential to be involved in salt stress response, especially, OsMSR2, whose orthologous genes in Arabidopsis had the potential role in photosynthesis adaptation under salt stress.
Slope Stability in a Multi-Hazard Eruption Scenario (Santorini, Greece)
Authors: Forte Giovanni , De Falco Melania , Santangelo Nicoletta , Santo Antonio
Published: September 2019

Under the European FP7 SNOWBALL project (2014–2017), the island of Santorini was used as a case study to validate a procedure to assess the possible multiple cascading effects caused by volcanic eruptions. From January 2011 to April 2012, the area was affected by low to moderate (Mw <3.2) seismic shaking, which caused concern regarding a possible volcanic eruption that ultimately failed to materialize. Assuming the worst-case scenario of a sub-Plinian eruption, this study provides insights into the approach adopted by the SNOWBALL project to identify the most critical areas (hot spots) for slope stability. Geological field surveys, thematic maps, and geomorphological data on aerial photos and landform interpretation were adopted to assess the static susceptibility. The eruption scenario is related to two different phenomena: a pre-eruption earthquake (Mw 5.2) and the subsequent ash fallout deposition following the prevailing winds. Landslide susceptibility in seismic conditions was assessed through the HAZUS approach and the estimate of Newmark displacements (u), while the critical areas for ash fallout mobilization were assessed adopting empirical relationships. The findings are summarized in a scenario map reporting the most critical areas and the infrastructures most vulnerable to such phenomena.
Neuromuscular Electrical Stimulation Plus Rehabilitative Exercise as a Treatment for Dysphagia in Stroke and Non-Stroke Patients in an NHS Setting: Feasibility and Outcomes
Authors: Martindale Nicola , Stephenson John , Pownall Sue
Published: September 2019

Dysphagia is a debilitating condition with significant consequences in terms of physical and mental health. This study demonstrates that it is feasible to provide an intensive therapy program combining neuromuscular electrical stimulation (NMES) with exercise against resistance in the treatment of dysphagia in a public healthcare setting. Thirty-one patients (17 stroke, 14 non-stroke) who experienced dysphagia with reduced laryngeal elevation completed the therapy program. After checking the data sets for comparability, it was deemed appropriate for the outcome data from these patients to be combined with that of 12 stroke patients previously reported to enable statistical analysis on a larger data set (n = 43). A repeated-measures ANOVA revealed a statistically significant increase in amount and variety of food a patient was able to take orally (FOIS) following completion of treatment (p < 0.001). There was no significant between-subject effect of stroke status (p = 0.43), or interaction between treatment and stroke status (p = 0.68). There was a significant improvement in secondary outcome measures of swallow safety with fluids (PAS) (p < 0.001) and swallow-related quality of life (Swal-Qol (p < 0.001). These findings indicate that the therapy program may be associated with reduced impairment in a subset of patients with dysphagia resulting from stroke and non-stroke atiologies, and the data will inform the design of future research to address unanswered questions.
Study of Iron Gall Inks, Ingredients and Paper Composition Using Non-Destructive Techniques
Authors: Corregidor Victoria , Viegas Rita , Ferreira Luís M. , Alves Luís C.
Published: September 2019

Old manuscripts are among the most important elements of the cultural and historical heritage of ancient knowledge. Unfortunately, many of them suffer from degradation, mostly those written with iron gall inks. In the present work, a study using non-destructive techniques was designed with the aim of analyzing the elemental composition and structural characteristics of iron gall inks, reproduced in laboratory, paper and their interaction when the ink is deposited on paper, inducing the paper degradation. Proton induced X-ray emission, X-ray diffraction and Fourier-transform infrared spectroscopy provided the elemental and structural information, and photography under infrared (IR) and ultraviolet (UV) light allowed the differentiation between manufactured inks. Results show that the first step of inked paper deterioration is due to acid-hydrolysis of the cellulose and the presence of reactive Fe(II) species by reducing the crystallinity index of the paper, which is affected depending on the ink recipe and the starting raw materials. These results will be useful to future studies on ancient documents written with iron gall inks, which suffer deterioration due to ink corrosion, and to differentiate between the different paper degradation mechanisms.
Intersections and Non-Intersections: A Protocol for Identifying Pedestrian Crash Risk Locations in GIS
Authors: Kang Mingyu , Moudon Anne Vernez , Kim Haena , Boyle Linda Ng
Published: September 2019

Intersection and non-intersection locations are commonly used as spatial units of analysis for modeling pedestrian crashes. While both location types have been previously studied, comparing results is difficult given the different data and methods used to identify crash-risk locations. In this study, a systematic and replicable protocol was developed in GIS (Geographic Information System) to create a consistent spatial unit of analysis for use in pedestrian crash modelling. Four publicly accessible datasets were used to identify unique intersection and non-intersection locations: Roadway intersection points, roadway lanes, legal speed limits, and pedestrian crash records. Two algorithms were developed and tested using five search radii (ranging from 20 to 100 m) to assess the protocol reliability. The algorithms, which were designed to identify crash-risk locations at intersection and non-intersection areas detected 87.2% of the pedestrian crash locations (r: 20 m). Agreement rates between algorithm results and the crash data were 94.1% for intersection and 98.0% for non-intersection locations, respectively. The buffer size of 20 m generally showed the highest performance in the analyses. The present protocol offered an efficient and reliable method to create spatial analysis units for pedestrian crash modeling. It provided researchers a cost-effective method to identify unique intersection and non-intersection locations. Additional search radii should be tested in future studies to refine the capture of crash-risk locations.
Contamination of Homes with Methamphetamine: Is Wipe Sampling Adequate to Determine Risk?
Authors: Wright Jackie , Walker G. Stewart , Ross Kirstin E.
Published: September 2019

Contamination of domestic dwellings from methamphetamine cooking or smoking is an increasing public health problem in many countries. To evaluate the extent of contamination, sampling generally focusses on the collection of surface wipe samples from walls and other surfaces of a potentially contaminated home. Here, we report the contamination levels of many household materials and items sampled from a home that was suspected to be the premises used to cook methamphetamine, it was then sold, lived in for several years by the new owners and then left unattended for several more years. Although the time since the cooking had taken place was significant (over five years), the levels of contamination were extremely high in both household items that were part of the house when cooking was taking place (blinds, carpets, walls, etc.) and also in articles brought to the house post-cooking (rugs, toys, beds, etc.). Both wipe sampling and analysis of bulk samples indicate that the methamphetamine is not breaking down or being removed and is transferred from contaminated to non-contaminated objects. These results raise questions about the adequacy of characterising contamination and of making decisions about the extent of remediation required based solely on surface wipe samples. Without fully understanding the extent of contamination that is present, not only on surfaces but within the building materials, it is difficult to ensure that the correct and most effective remedial approaches are taken to appropriately determine and address the risks to inhabitants.
Child Victimization in the Context of Family Violence
Authors: Chan Ko Ling
Published: September 2019

Child victimization refers to all possible forms of violence experienced by a child. This issue examines multiple types of victimization through a comprehensive approach. To understand child victimization fully, it should be investigated within the context of family violence. The studies in this issue provide evidence of the prevalence of various types of child victimization. As well as child maltreatment and bullying, the emerging form of cyberbullying is examined in several studies. The family has always been the main focus around child victimization, with parenting style as one prominent example. Studies show that some parenting styles are associated with child maltreatment and therefore have suggested that parenting programs may be effective in reducing child victimization. This issue provides up-to-date studies from different regions around the world. It makes a significant contribution to the current debate in child victimization.
Effects of Orientations, Aspect Ratios, Pavement Materials and Vegetation Elements on Thermal Stress inside Typical Urban Canyons
Authors: Lobaccaro Gabriele , Acero Juan Angel , Sanchez Martinez Gerardo , Padro Ales , Laburu Txomin , Fernandez German
Published: September 2019

The analysis of local climate conditions to test artificial urban boundaries and related climate hazards through modelling tools should become a common practice to inform public authorities about the benefits of planning alternatives. Different finishing materials and sheltering objects within urban canyons (UCs) can be tested, predicted and compared through quantitative and qualitative understanding of the relationships between the microclimatic environment and subjective thermal assessment. This process can work as support planning instrument in the early design phases as has been done in this study that aims to analyze the thermal stress within typical UCs of Bilbao (Spain) in summertime through the evaluation of Physiologically Equivalent Temperature using ENVI-met. The UCs are characterized by different orientations, height-to-width aspect ratios, pavement materials, trees’ dimensions and planting pattern. Firstly, the current situation was analyzed; secondly, the effects of asphalt and red brick stones as streets’ pavement materials were compared; thirdly, the benefits of vegetation elements were tested. The analysis demonstrated that orientation and aspect ratio strongly affect the magnitude and duration of the thermal peaks at pedestrian level; while the vegetation elements improve the thermal comfort up to two thermophysiological assessment classes. The outcomes of this study, were transferred and visualized into green planning recommendations for new and consolidated urban areas in Bilbao.
Predicting Behavioral Intentions Related to Cervical Cancer Screening Using a Three-Level Model for the TPB and SCT in Nanjing, China
Authors: Zhang Jianxin , Sha Zimo , Gu Yuzhou , Li Yanzhang , Yang Qinlan , Zhu Yuxuan , He Yuan
Published: September 2019

Objective: Exploring how the theory of planned behavior (TPB), social capital theory (SCT), cervical cancer knowledge (CCK), and demographic variables predict behavioral intentions (BI) related to cervical cancer screening among Chinese women. Methods: Self-administered questionnaires were distributed to 496 women, followed by a path analysis. Results: The three-level model was acceptable, χ2(26, 470) = 26.93, p > 0.05. Subjectively overcoming difficulties, support from significant others, screening necessity, and the objective promotion factor promoted BI, with effect sizes of 0.424, 0.354, 0.199, and 0.124. SCT and CCK promoted BI through TPB, with effect sizes of 0.262 and 0.208. Monthly income, education, age, and childbearing condition affected BI through TPB, SCT, and CCK, with effect sizes of 0.269, 0.105, 0.065, and −0.029. Conclusion: The three-level model systematically predicted behavioral intentions relating to cervical cancer screening.
Proteomics of PTI and Two ETI Immune Reactions in Potato Leaves
Authors: Resjö Svante , Zahid Muhammad Awais , Burra Dharani Dhar , Lenman Marit , Levander Fredrik , Andreasson Erik
Published: September 2019

Plants have a variety of ways to defend themselves against pathogens. A commonly used model of the plant immune system is divided into a general response triggered by pathogen-associated molecular patterns (PAMPs), and a specific response triggered by effectors. The first type of response is known as PAMP triggered immunity (PTI), and the second is known as effector-triggered immunity (ETI). To obtain better insight into changes of protein abundance in immunity reactions, we performed a comparative proteomic analysis of a PTI and two different ETI models (relating to Phytophthora infestans) in potato. Several proteins showed higher abundance in all immune reactions, such as a protein annotated as sterol carrier protein 2 that could be interesting since Phytophthora species are sterol auxotrophs. RNA binding proteins also showed altered abundance in the different immune reactions. Furthermore, we identified some PTI-specific changes of protein abundance, such as for example, a glyoxysomal fatty acid beta-oxidation multifunctional protein and a MAR-binding protein. Interestingly, a lysine histone demethylase was decreased in PTI, and that prompted us to also analyze protein methylation in our datasets. The proteins upregulated explicitly in ETI included several catalases. Few proteins were regulated in only one of the ETI interactions. For example, histones were only downregulated in the ETI-Avr2 interaction, and a putative multiprotein bridging factor was only upregulated in the ETI-IpiO interaction. One example of a methylated protein that increased in the ETI interactions was a serine hydroxymethyltransferase.
Toll-Like Receptors-2 and -4 in Graves’ Disease—Key Players or Bystanders?
Authors: Polak Agnieszka , Grywalska Ewelina , Klatka Janusz , Roliński Jacek , Matyjaszek-Matuszek Beata , Klatka Maria
Published: September 2019

Graves’ disease (GD) is an autoimmune disease that affects the thyroid. The development of autoimmunity is associated with innate immune responses where the prominent role plays Toll-like receptors (TLRs). The aim of our study was to assess the relationship between the expression levels of TLR-2 and TLR-4 on CD4+ and CD8+ T as well as CD19+ B lymphocytes in patients with GD and selected clinical parameters. The study group consisted of 32 women with GD, the control group consisted of 20 healthy women. Immunophenotyping was performed using the flow cytometry and cytokines concentrations were assessed using ELISA assay. The mean percentage of CD4+/TLR-2+ and CD8+/TLR-2+ T cells in patients with GD was higher than in the control group (p < 0.0001). After obtaining euthyroidism, the mean percentage of CD4+/TLR-2+ T cells in patients with GD decreased (p < 0.0001). The expression level of TLR-2 on CD4+ T lymphocytes correlated with serum FT3 concentration in patients with GD (r = 0.47, p = 0.007). The mean percentage of CD8+/TLR-2+ T cells in patients with GD before treatment compared to patients with GD after obtaining euthyroidism was higher (p = 0.0163). Similar findings were found for TLR-4. Thus the TLR-2 and TLR-4 can be a prognostic marker for Graves’ disease.
Extracellular Albumin Covalently Sequesters Selenocompounds and Determines Cytotoxicity
Authors: Zheng Wenyi , Boada Roberto , He Rui , Xiao Tingting , Ye Fei , Simonelli Laura , Valiente Manuel , Zhao Ying , Hassan Moustapha
Published: September 2019

Selenocompounds (SeCs) are well-known nutrients and promising candidates for cancer therapy; however, treatment efficacy is very heterogeneous and the mechanism of action is not fully understood. Several SeCs have been reported to have albumin-binding ability, which is an important factor in determining the treatment efficacy of drugs. In the present investigation, we hypothesized that extracellular albumin might orchestrate SeCs efficacy. Four SeCs representing distinct categories were selected to investigate their cytotoxicity, cellular uptake, and species transformation. Concomitant treatment of albumin greatly decreased cytotoxicity and cellular uptake of SeCs. Using both X-ray absorption spectroscopy and hyphenated mass spectrometry, we confirmed the formation of macromolecular conjugates between SeCs and albumin. Although the conjugate was still internalized, possibly via albumin scavenger receptors expressed on the cell surface, the uptake was strongly inhibited by excess albumin. In summary, the present investigation established the importance of extracellular albumin binding in determining SeCs cytotoxicity. Due to the fact that albumin content is higher in humans and animals than in cell cultures, and varies among many patient categories, our results are believed to have high translational impact and clinical implications.
The Antioxidant and Antiproliferative Activities of 1,2,3-Triazolyl-L-Ascorbic Acid Derivatives
Authors: Harej Anja , Macan Andrijana Meščić , Stepanić Višnja , Klobučar Marko , Pavelić Krešimir , Pavelić Sandra Kraljević , Raić-Malić Silvana
Published: September 2019

The novel 4-substituted 1,2,3-triazole L-ascorbic acid (L-ASA) conjugates with hydroxyethylene spacer as well as their conformationally restricted 4,5-unsaturated analogues were synthesized as potential antioxidant and antiproliferative agents. An evaluation of the antioxidant activity of novel compounds showed that the majority of the 4,5-unsaturated L-ASA derivatives showed a better antioxidant activity compared to their saturated counterparts. m-Hydroxyphenyl (7j), p-pentylphenyl (7k) and 2-hydroxyethyl (7q) substituted 4,5-unsaturated 1,2,3-triazole L-ASA derivatives exhibited very efficient and rapid (within 5 min) 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radical scavenging activity (7j, 7k: IC50 = 0.06 mM; 7q: IC50 = 0.07 mM). In vitro scavenging activity data were supported by in silico quantum-chemical modelling. Thermodynamic parameters for hydrogen-atom transfer and electron-transfer radical scavenging pathways of anions deprotonated at C2-OH or C3-OH groups of L-ASA fragments were calculated. The structure activity analysis (SAR) through principal component analysis indicated radical scavenging activity by the participation of OH group with favorable reaction parameters: the C3-OH group of saturated C4-C5(OH) derivatives and the C2-OH group of their unsaturated C4=C5 analogues. The antiproliferative evaluation showed that p-bromophenyl (4e: IC50 = 6.72 μM) and p-pentylphenyl-substituted 1,2,3-triazole L-ASA conjugate (4k: IC50 = 26.91 μM) had a selective cytotoxic effect on breast adenocarcinoma MCF-7 cells. Moreover, compound 4e did not inhibit the growth of foreskin fibroblasts (IC50 > 100 μM). In MCF-7 cells treated with 4e, a significant increase of hydroxylated hypoxia-inducible transcription factor 1 alpha (HIF-1α) expression and decreased expression of nitric oxide synthase 2 (NOS2) were observed, suggesting the involvement of 4e in the HIF-1α signaling pathway for its strong growth-inhibition effect on MCF-7 cells.
Leptin and Associated Mediators of Immunometabolic Signaling: Novel Molecular Outcome Measures for Neurostimulation to Treat Chronic Pain
Authors: Kinfe Thomas , Buchfelder Michael , Chaudhry Shafqat , Chakravarthy Krishnan , Deer Timothy , Russo Marc , Georgius Peter , Hurlemann Rene , Rasheed Muhammad , Muhammad Sajjad , Yearwood Thomas
Published: September 2019

Chronic pain is a devastating condition affecting the physical, psychological, and socioeconomic status of the patient. Inflammation and immunometabolism play roles in the pathophysiology of chronic pain disorders. Electrical neuromodulation approaches have shown a meaningful success in otherwise drug-resistant chronic pain conditions, including failed back surgery, neuropathic pain, and migraine. A literature review (PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles) was performed using the following search terms: chronic pain disorders, systemic inflammation, immunometabolism, prediction, biomarkers, metabolic disorders, and neuromodulation for chronic pain. Experimental studies indicate a relationship between the development and maintenance of chronic pain conditions and a deteriorated immunometabolic state mediated by circulating cytokines, chemokines, and cellular components. A few uncontrolled in-human studies found increased levels of pro-inflammatory cytokines known to drive metabolic disorders in chronic pain patients undergoing neurostimulation therapies. In this narrative review, we summarize the current knowledge and possible relationships of available neurostimulation therapies for chronic pain with mediators of central and peripheral neuroinflammation and immunometabolism on a molecular level. However, to address the needs for predictive factors and biomarkers, large-scale databank driven clinical trials are needed to determine the clinical value of molecular profiling.
The CXCR4–CXCL12-Axis Is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects In Vitro
Authors: Pansy Katrin , Feichtinger Julia , Ehall Barbara , Uhl Barbara , Sedej Miriam , Roula David , Pursche Beata , Wolf Axel , Zoidl Manuel , Steinbauer Elisabeth , Gruber Verena , Greinix Hildegard T , Prochazka Katharina T. , Thallinger Gerhard G. , Heinemann Akos , Beham-Schmid Christine , Neumeister Peter , Wrodnigg Tanja M. , Fechter Karoline , Deutsch Alexander JA.
Published: September 2019

In tumor cells of more than 20 different cancer types, the CXCR4-CXCL12-axis is involved in multiple key processes including proliferation, survival, migration, invasion, and metastasis. Since data on this axis in diffuse large B cell lymphoma (DLBCL) are inconsistent and limited, we comprehensively studied the CXCR4-CXCL12-axis in our DLBCL cohort as well as the effects of CXCR4 antagonists on lymphoma cell lines in vitro. In DLBCL, we observed a 140-fold higher CXCR4 expression compared to non-neoplastic controls, which was associated with poor clinical outcome. In corresponding bone marrow biopsies, we observed a correlation of CXCL12 expression and lymphoma infiltration rate as well as a reduction of CXCR4 expression in remission of bone marrow involvement after treatment. Additionally, we investigated the effects of three CXCR4 antagonists in vitro. Therefore, we used AMD3100 (Plerixafor), AMD070 (Mavorixafor), and WKI, the niacin derivative of AMD070, which we synthesized. WK1 demonstrated stronger pro-apoptotic effects than AMD070 in vitro and induced expression of pro-apoptotic genes of the BCL2-family in CXCR4-positive lymphoma cell lines. Finally, WK1 treatment resulted in the reduced expression of JNK-, ERK1/2- and NF-κB/BCR-target genes. These data indicate that the CXCR4-CXCL12-axis impacts the pathogenesis of DLBCL and represents a potential therapeutic target in aggressive lymphomas.
Causes and Consequences of A Glutamine Induced Normoxic HIF1 Activity for the Tumor Metabolism
Authors: Kappler Matthias , Pabst Ulrike , Weinholdt Claus , Taubert Helge , Rot Swetlana , Kaune Tom , Kotrba Johanna , Porsch Martin , Güttler Antje , Bache Matthias , Krohn Knut , Bull Fabian , Riemann Anne , Wickenhauser Claudia , Seliger Barbara , Schubert Johannes , Al-Nawas Bilal , Thews Oliver , Grosse Ivo , Vordermark Dirk , Eckert Alexander W.
Published: September 2019

The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of genes that are involved in metabolism under hypoxic conditions, but information regarding the transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated under normoxic and hypoxic conditions with various drugs that affect cellular metabolism. HIF1α was silenced by siRNA in normoxic/hypoxic tumor cells, before RNA sequencing and bioinformatics analyses were performed while using the breast cancer cell line MDA-MB-231 as a model. Differentially expressed genes were further analyzed and validated by qPCR, while the activity of the metabolites was determined by enzyme assays. Under normoxic conditions, HIF1 activity was significantly increased by (i) glutamine metabolism, which was associated with the release of ammonium, and it was decreased by (ii) acetylation via acetyl CoA synthetase (ACSS2) or ATP citrate lyase (ACLY), respectively, and (iii) the presence of L-ascorbic acid, citrate, or acetyl-CoA. Interestingly, acetylsalicylic acid, ibuprofen, L-ascorbic acid, and citrate each significantly destabilized HIF1α only under normoxia. The results from the deep sequence analyses indicated that, in HIF1-siRNA silenced MDA-MB-231 cells, 231 genes under normoxia and 1384 genes under hypoxia were transcriptionally significant deregulated in a HIF1-dependent manner. Focusing on glycolysis genes, it was confirmed that HIF1 significantly regulated six normoxic and 16 hypoxic glycolysis-associated gene transcripts. However, the results from the targeted metabolome analyses revealed that HIF1 activity affected neither the consumption of glucose nor the release of ammonium or lactate; however, it significantly inhibited the release of the amino acid alanine. This study comprehensively investigated, for the first time, how normoxic HIF1 is stabilized, and it analyzed the possible function of normoxic HIF1 in the transcriptome and metabolic processes of tumor cells in a breast cancer cell model. Furthermore, these data imply that HIF1 compensates for the metabolic outcomes of glutaminolysis and, subsequently, the Warburg effect might be a direct consequence of the altered amino acid metabolism in tumor cells.
Cloning and Functional Characterization of Dihydroflavonol 4-Reductase Gene Involved in Anthocyanidin Biosynthesis of Grape Hyacinth
Authors: Liu Hongli , Lou Qian , Ma Junren , Su Beibei , Gao Zhuangzhuang , Liu Yali
Published: September 2019

Grape hyacinth (Muscari spp.) is a popular ornamental plant with bulbous flowers noted for their rich blue color. Muscari species have been thought to accumulate delphinidin and cyanidin rather than pelargonidin-type anthocyanins because their dihydroflavonol 4-reductase (DFR) does not efficiently reduce dihydrokaempferol. In our study, we clone a novel DFR gene from blue flowers of Muscari. aucheri. Quantitative real-time PCR (qRT-PCR) and anthocyanin analysis showed that the expression pattern of MaDFR had strong correlations with the accumulation of delphinidin, relatively weak correlations with cyanidin, and no correations with pelargonidin. However, in vitro enzymatic analysis revealed that the MaDFR enzyme can reduce all the three types of dihydroflavonols (dihydrokaempferol, dihydroquercetin, and dihydromyricetin), although it most preferred dihydromyricetin as a substrate to produce leucodelphinidin, the precursor of blue-hued delphinidin. This indicated that there may be other functional genes responsible for the loss of red pelargonidin-based pigments in Muscari. To further verify the substrate-specific selection domains of MaDFR, an assay of amino acid substitutions was conducted. The activity of MaDFR was not affected whenever the N135 or E146 site was mutated. However, when both of them were mutated, the catalytic activity of MaDFR was lost completely. The results suggest that both the N135 and E146 sites are essential for the activity of MaDFR. Additionally, the heterologous expression of MaDFR in tobacco (Nicotiana tabacum) resulted in increasing anthocyanin accumulation, leading to a darker flower color, which suggested that MaDFR was involved in color development in flowers. In summary, MaDFR has a high preference for dihydromyricetin, and it could be a powerful candidate gene for genetic engineering for blue flower colour modification. Our results also make a valuable contribution to understanding the basis of color variation in the genus Muscari.
Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line
Authors: Cammarata Francesco P , Torrisi Filippo , Forte Giusi I , Minafra Luigi , Bravatà Valentina , Pisciotta Pietro , Savoca Gaetano , Calvaruso Marco , Petringa Giada , Cirrone Giuseppe A. P. , Fallacara Anna L , Maccari Laura , Botta Maurizio , Schenone Silvia , Parenti Rosalba , Cuttone Giacomo , Russo Giorgio
Published: September 2019

Glioblastoma Multiforme (GBM) is the most common of malignant gliomas in adults with an exiguous life expectancy. Standard treatments are not curative and the resistance to both chemotherapy and conventional radiotherapy (RT) plans is the main cause of GBM care failures. Proton therapy (PT) shows a ballistic precision and a higher dose conformity than conventional RT. In this study we investigated the radiosensitive effects of a new targeted compound, SRC inhibitor, named Si306, in combination with PT on the U87 glioblastoma cell line. Clonogenic survival assay, dose modifying factor calculation and linear-quadratic model were performed to evaluate radiosensitizing effects mediated by combination of the Si306 with PT. Gene expression profiling by microarray was also conducted after PT treatments alone or combined, to identify gene signatures as biomarkers of response to treatments. Our results indicate that the Si306 compound exhibits a radiosensitizing action on the U87 cells causing a synergic cytotoxic effect with PT. In addition, microarray data confirm the SRC role as the main Si306 target and highlights new genes modulated by the combined action of Si306 and PT. We suggest, the Si306 as a new candidate to treat GBM in combination with PT, overcoming resistance to conventional treatments.
Turbine Cascades of Last Stage Blades for Wide Range of Operating Conditions
Authors: Novak Ondrej , Bobcik Marek , Luxa Martin , Fort Jaroslav , Rudas Bartolomej , Synac Jaroslav , Simurda David , Furst Jiri , Halama Jan , Hric Vladimir , Prihoda Jaromir , Simka Zdenek
Published: September 2019

Recent trends in the electric energy market such as biomass, waste incineration or combined cycle power plants require innovative solutions in steam turbine design. Variable operating conditions cause significant changes in flow field surrounding the steam turbine last stage blades. Therefore, the enlargement of operating range for last stage blades presents new challenges in design of turbine cascades. Several turbine cascades were designed and analyzed by commercial and in-house software of CTU Prague. Selected profiles were experimentally validated in the high-speed wind tunnel for 2D cascade measurements of the Institute of Thermomechanics of the Czech Academy of Sciences which is equipped by an adjustable supersonic inlet nozzle, perforated inserts at side walls and adjustable perforated tailboard. Comparisons are presented of numerical results with optical and pneumatic measurements for a wide range of inlet and outlet Mach numbers for optimized hub and tip profile cascades.
Hybrid Optimization Algorithm for Bayesian Network Structure Learning
Authors: Sun Xingping , Chen Chang , Wang Lu , Kang Hongwei , Shen Yong , Chen Qingyi
Published: September 2019

Since the beginning of the 21st century, research on artificial intelligence has made great progress. Bayesian networks have gradually become one of the hotspots and important achievements in artificial intelligence research. Establishing an effective Bayesian network structure is the foundation and core of the learning and application of Bayesian networks. In Bayesian network structure learning, the traditional method of utilizing expert knowledge to construct the network structure is gradually replaced by the data learning structure method. However, as a result of the large amount of possible network structures, the search space is too large. The method of Bayesian network learning through training data usually has the problems of low precision or high complexity, which make the structure of learning differ greatly from that of reality, which has a great influence on the reasoning and practical application of Bayesian networks. In order to solve this problem, a hybrid optimization artificial bee colony algorithm is discretized and applied to structure learning. A hybrid optimization technique for the Bayesian network structure learning method is proposed. Experimental simulation results show that the proposed hybrid optimization structure learning algorithm has better structure and better convergence.
Gallbladder Radiation Protection in SIRT—Quantitative Anatomical Study of Hepatic Vasculature
Authors: Piasecki Piotr , Brzozowski Krzysztof , Ziecina Piotr , Wierzbicki Marek , Budzynska Anna , Mazurek Andrzej , Dziuk Miroslaw , Maciak Maciej , Iller Edward , Narloch Jerzy
Published: September 2019

Introduction: This study was designed to assess quantitatively a safe position of the microcatheter during the SIRT (Selective Internal Radiation Therapy) procedure, in order to minimize the risk of non-target spheres leaking. Materials and Methods: Retrospective analysis of the distance of the tip of the microcatheter from coiled or patent non-target arteries was measured during 99mTc-MAA work-up procedure. Frequency of extrahepatic leaking during work-up and SIRT procedures was evaluated. Results: There were 85 patients who underwent 98 work-up procedures. There were 64 radioembolizations. There were 44 gastroduodenal, 51 right gastric, and 54 cystic artery embolizations performed. Extrahepatic 99mTc-MAA leaking was observed in 33 cases: 16 to gallbladder, four to a gastric wall, nine to the duodenum, one to the intestinal wall, and three to the abdominal wall. Leak in 99mTc-MAA was also related to the presence of additional arteries (p = 0.009). There were 34 proximal and 31 distal to cystic artery 99mTc-MAA injections resulting in 12 vs. four leaks, respectively (p = 0.039, RR-2.5). Mean distance of the tip of the microcatheter from the origin of the cystic artery was 20 mm (minimum of 2.1 mm and maximum of 53 mm) proximally and 10 mm (minimum 1 mm and maximum 51 mm) distally (ns). Conclusions: Leaking in 99mTc-MAA (99mTc - labelled macroaggregated albumin) was related to the presence of additional arteries. Regardless of cystic artery embolization, it is 2.5 times safer to inject microspheres distal to its origin, compared to proximal injection. Cystic artery origin relative to the right hepatic artery division usually necessitates embolization of the former.
Coastal Retreat and Sedimentation during the Last 3000 Years. Atlantic Coast of NW Spain
Authors: Blanco-Chao Ramón , Costa-Casais Manuela , Cajade-Pascual Daniel , Gómez-Rey Gonzalo
Published: September 2019

During the last glaciation, thick nival and periglacial sediments buried large sectors of the NW coast of Spain. The sediments were mostly eroded by the rising sea level during the Holocene, but in several places they remain, forming sedimentary cliffs. Radiocarbon dates obtained at the topmost layers of these cliffs prove that continental sedimentation was active until very recent times, followed by a retreat of the cliffs. During the first stages of the transgression, the erosion of the cliffs and the changes in the coastal system were controlled by the rising sea-level. Once the sea-level stabilized, the exhumation of inherited landforms, the supply of sediments, and a continuous continental sedimentation became the main factors. The last stages of cliff retreat were almost synchronous with the sedimentation of the upper layers of the deposits.