bluuebunny/crossref_metadata_2025 huggingface dataset:
Ammonium Sorbed to Zeolite Is Partly Available to Wheat in the First Growth Cycle
Authors: Foereid Bente , Alvarenga Emilio , Szocs Julia , Makadi Marianna
Published: March 2019

Sorption could be a way to concentrate nutrients in diluted waste streams to bring more nutrients back to agriculture. However, the sorbed nutrients must be plant available. The aim of this work was to investigate how plant available nitrogen (N) added sorbed to zeolite and is compared to conventionally added N. First, 15N labelled ammonium was sorbed to a sorbent, zeolite, in an aqueous solution. Then, the fertilizer effect was compared to the ammonium fertilizer and added the conventional way, with and without zeolite. A pot experiment with two soil types (chernozem and sandy soil) and wheat as test crop was used. Results indicated that the fertilizer effect of sorbed ammonium in the first growth cycle is about 50% of ammonium added conventionally. The sorbent itself had a positive effect in sandy soil, but not in chernozem. N uptake without added N was higher in chernozem than in sandy soil and more N from fertilizer was left in the soil after the experiment in the chernozem than in the sandy soil. In conclusion, ammonium added sorbed is plant available to some extent, but less so than conventionally added ammonium.
Immunogenicity of Innovative and Biosimilar Monoclonal Antibodies
Authors: Doevendans Erik , Schellekens Huub
Published: March 2019

The development of hybridoma technology for producing monoclonal antibodies (mAbs) by Kohler and Milstein (1975) counts as one of the major medical breakthroughs, opening up endless possibilities for research, diagnosis and for treatment of a whole variety of diseases. Therapeutic mAbs were introduced three decades ago. The first generation of therapeutic mAbs of murine origin showed high immunogenicity, which limited efficacy and was associated with severe infusion reactions. Subsequently chimeric, humanized, and fully human antibodies were introduced as therapeutics, these mAbs were considerably less immunogenic. Unexpectedly humanized mAbs generally show similar immunogenicity as chimeric antibodies; based on sequence homology chimeric mAbs are sometimes more “human” than humanized mAbs. With the introduction of the regulatory concept of similar biological medicines (biosimilars) a key concern is the similarity in terms of immunogenicity of these biosimilars with their originators. This review focuses briefly on the mechanisms of induction of immunogenicity by biopharmaceuticals, mAbs in particular, in relation to the target of the immune system.
Evaluation of the AGE/sRAGE Axis in Patients with Multiple Myeloma
Authors: Allegra Alessandro , Musolino Caterina , Pace Elisabetta , Innao Vanessa , Di Salvo Eleonora , Ferraro Maria , Casciaro Marco , Spatari Giovanna , Tartarisco Gennaro , Allegra Andrea Gaetano , Gangemi Sebastiano
Published: March 2019

Glycative stress influences tumor progression. The aim of the present study was to evaluate the advanced glycation end products/soluble receptor of advanced glycation end products (AGE/sRAGE) axis in patients with multiple myeloma (MM). Blood samples were taken from 19 patients affected by MM and from 16 sex-matched and age-matched healthy subjects. AGE and sRAGE axis were dosed in patients with MM and matched with controls. AGEs were measured by spectrofluorimetric methods. Blood samples for the determination of sRAGE were analyzed by ELISA. AGE levels were significantly reduced in patients with respect to controls. Instead, sRAGE was significantly elevated in patients affected by MM compared to healthy subjects. Moreover, we showed that there was a statistically significant difference in sRAGE according to the heavy and light chain. IgA lambda had significantly higher sRAGE values than IgA kappa, IgG kappa, and IgG Lambda MM patients. From our data emerges the role of the sRAGE/AGE axis in MM. Since AGE is a positive regulator of the activity of RAGE, circulating sRAGE concentrations may reflect RAGE expression and may be raised in parallel with serum AGE concentrations as a counter-system against AGE-caused tissue damage. Serum concentrations of AGE and sRAGE could therefore become potential therapeutic targets.
Regulation of Smooth Muscle Cell Proliferation by NADPH Oxidases in Pulmonary Hypertension
Authors: Huetsch John C. , Suresh Karthik , Shimoda Larissa A.
Published: March 2019

Hyperproliferation of pulmonary arterial smooth muscle cells is a key component of vascular remodeling in the setting of pulmonary hypertension (PH). Numerous studies have explored factors governing the changes in smooth muscle cell phenotype that lead to the increased wall thickness, and have identified various potential candidates. A role for reactive oxygen species (ROS) has been well documented in PH. ROS can be generated from a variety of sources, including mitochondria, uncoupled nitric oxide synthase, xanthine oxidase, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In this article, we will review recent data supporting a role for ROS generated from NADPH oxidases in promoting pulmonary arterial smooth muscle cell proliferation during PH.
Remote Thermoelastic Characterization of Candidate Structural and Protective Coatings for Lead-Bismuth Eutectic Cooled Nuclear Reactors
Authors: Verstraeten Bert , Sermeus Jan , Van der Donck Tom , Schuurmans Paul , Glorieux Christ
Published: March 2019

A laser ultrasonics approach to remotely characterize the elastic and thermal properties of a coating-substrate structure, used to protect fuel claddings in lead-bismuth eutectic cooled nuclear reactors, is presented and validated with experimental results. A transient grating geometry is used for multiple wavelength excitation of thermoelastic displacements, and laser beam deflection for detection. The value of Young’s modulus of the coating layer as calculated from the coating’s Rayleigh velocity of 190 ± 50 GPa is in accordance with a nano-indentation measurement. Using a priori knowledge concerning the density and elastic parameters of the coating and substrate, scanning the sample allows the obtaining of a coating thickness map in a fully remote, all-optical way, with an accuracy of about 4 microns for a coating of around 20-micron average thickness. Analyzing the transient thermal grating decay yields a thermal diffusivity value of ( 5.0 ± 1.6 ) × 10 − 6 m 2 /s, in the range of low-carbon steels. The consistency of the results infers that the all-optical laser ultrasonics approach should be feasible for remote inspection of the quality of optically rough coated claddings in the harsh environment of a nuclear reactor.
Thermal Analysis of Cornea Heated with Terahertz Radiation
Authors: Liu Wenquan , Lu Yuanfu , She Rongbin , Wei Guanglu , Jiao Guohua , Lv Jiancheng , Li Guangyuan
Published: March 2019

We numerically investigate the thermal effects in a cornea illuminated by terahertz radiation. By modifying the bioheat and Arrhenius equations, we studied the heat-transfer and temperature distributions in the corneal tissue, and evaluated the potential thermal damage. The influence of the beam radius and power density are discussed. We also estimated the effective cornea-collagen shrinkage region, and evaluated the degree of thermal damage in the cornea. We expect this work to open up a novel effective and safe thermal-treatment approach based on THz radiation for cornea reshaping in the field of ophthalmology.
Lifetime Assessment and Optimization of a Welded A-Type Frame in a Mining Truck Considering Uncertainties of Material Properties and Structural Geometry and Load
Authors: Mi Chengji , Li Wentai , Xiao Xuewen , Jian Haigen , Gu Zhengqi , Berto Filippo
Published: March 2019

In order to improve the fatigue performance of a welded A-type frame in a heavy off-road mining truck, a novel method was presented to implement lifetime and weight collaborative optimization while considering uncertainties in geometry dimension, material properties, and bearing load. The mechanical and cyclic material parameters were obtained from experimental work to characterize the base metal and the weldment. The finite element model of a welded A-type frame was constructed to analyze stress distribution and predict fatigue life, the force time histories of which were acquired from multi-body dynamics simulation. The simulated failure position and fatigue life had a good agreement with the actual results. Then, both structural lifetime and weight were considered as optimization objectives. The thickness of main steel plates and elastic and cyclic material parameters were chosen as uncertain design variables as well as main loads at connection locations. The fifty sample points in the light of Latin hypercube sampling method and its responses calculated by finite element analysis were supposed to build the approximation model based on the Kriging approximation method. After its fitting precision was guaranteed, the non-dominated sorting genetic algorithm II (NSGA-II) was utilized to find the optimal solution. Finally, the fatigue life of a welded A-type frame was increased to 2.40 × 105 cycles and its mass was lessened by 8.2%. The optimized results implied that good fatigue performance of this welded A-type frame needs better welding quality, lower running speed for downhill and turning road surface, and thicker front plates.
The Optimization of Cold Rubidium Atom Two-Photon Transition Excitation with an Erbium-Fiber Optical Frequency Comb
Authors: Lu Haoyuan , Leng Jianxiao , Zhao Jianye
Published: March 2019

We demonstrated the observation of cold rubidium atom two-photon transition excitation by a fiber optical frequency comb. In addition to this, we optimized the repetition rate of optical frequency comb to enhance two-photon intensity by controlling cavity length and pump source of optical comb. This technique can fine tune repetition rate to corresponding stepwise two-photon transition resonance frequency and improve the transition intensity by three times. This method is useful in Doppler laser cooling and detection of macromolecules.
CPES Testing with mosaik: Co-Simulation Planning, Execution and Analysis
Authors: Steinbrink Cornelius , Blank-Babazadeh Marita , El-Ama André , Holly Stefanie , Lüers Bengt , Nebel-Wenner Marvin , Ramírez Acosta Rebeca P. , Raub Thomas , Schwarz Jan Sören , Stark Sanja , Nieße Astrid , Lehnhoff Sebastian
Published: March 2019

The complex nature of cyber-physical energy systems (CPES) makes systematic testing of new technologies for these setups challenging. Co-simulation has been identified as an efficient and flexible test approach that allows consideration of interdisciplinary dynamic interactions. However, basic coupling of simulation models alone fails to account for many of the challenges of simulation-based multi-domain testing such as expert collaboration in test planning. This paper illustrates an extended CPES test environment based on the co-simulation framework mosaik. The environment contains capabilities for simulation planning, uncertainty quantification and the development of multi-agent systems. An application case involving virtual power plant control is used to demonstrate the platform’s features. Future extensibility of the highly modular test environment is outlined.
Multi-Robot Trajectory Planning and Position/Force Coordination Control in Complex Welding Tasks
Authors: Gan Yahui , Duan Jinjun , Chen Ming , Dai Xianzhong
Published: March 2019

In this paper, the trajectory planning and position/force coordination control of multi-robot systems during the welding process are discussed. Trajectory planning is the basis of the position/ force cooperative control, an object-oriented hierarchical planning control strategy is adopted firstly, which has the ability to solve the problem of complex coordinate transformation, welding process requirement and constraints, etc. Furthermore, a new symmetrical internal and external adaptive variable impedance control is proposed for position/force tracking of multi-robot cooperative manipulators. Based on this control approach, the multi-robot cooperative manipulator is able to track a dynamic desired force and compensate for the unknown trajectory deviations, which result from external disturbances and calibration errors. In the end, the developed control scheme is experimentally tested on a multi-robot setup which is composed of three ESTUN industrial manipulators by welding a pipe-contact-pipe object. The simulations and experimental results are strongly proved that the proposed approach can finish the welding task smoothly and achieve a good position/force tracking performance.
A Quantitative Index to Evaluate the Commutation Failure Probability of LCC-HVDC with a Synchronous Condenser
Authors: Sha Jiangbo , Guo Chunyi , Rehman Atiq Ur , Zhao Chengyong
Published: March 2019

Since thyristor cannot turn off automatically, line commutated converter based high voltage direct current (LCC-HVDC) will inevitably fail to commutate and therefore auxiliary controls or voltage control devices are needed to improve the commutation failure immunity of the LCC-HVDC system. The voltage control device, a synchronous condenser (SC), can effectively suppress the commutation failure of the LCC-HVDC system. However, there is a need for a proper evaluation index that can quantitatively assess the ability of the LCC-HVDC system to resist the occurrence of commutation failures. At present, the main quantitative evaluation indicators include the commutation failure immunity index and the commutation failure probability index. Although they can reflect the resistance of the LCC-HVDC system to commutation failures to a certain extent, they are all based on specific working conditions and cannot comprehensively evaluate the impact of SCs on suppressing the commutation failure of the LCC-HVDC system under certain fault ranges. In order to more comprehensively and quantitatively evaluate the influence of SCs on the commutation failure susceptibility of the LCC-HVDC system under certain fault ranges, this paper proposes the area ratio of commutation failure probability. The accuracy of this new index was verified through the PSCAD/EMTDC. Based on the CIGRE benchmark model, the effects of different synchronous condensers on LCC-HVDC commutation failure were analyzed. The results showed that the new index could effectively and more precisely evaluate the effect of SCs on commutation failures. Moreover, the proposed index could provide a theoretical basis for the capacity allocation of SCs in practical projects and it could also be utilized for evaluating the impact of other dynamic reactive power compensators on the commutation failure probability of the LCC-HVDC system under certain fault ranges.
Detection of Additives with the Help of Discrete Geometrical Invariants
Authors: Nigmatullin Raoul , Vorobev Artem , Budnikov Herman , Sidelnikov Artem , Maksyutova Elza
Published: March 2019

In this paper, we propose a general mathematical method for the detection of electrochemical additives in a given solute with the help of discrete geometrical invariants (DGI). This idea is based on the generalization of Pythagor’s theorem that can be proved for two random sets located in the two-dimensional (2D) plane. This statement follows from the previous ideas proposed by Babenko, who essentially modernized the well-known theorem and propagated it on a wide class of “right” discrete sets with different symmetry. However, attentive analysis of these results shows that there is a possibility for their further generalization. For practical purposes, it is important to have discrete and deterministic curve(s) with the limited number of parameters that enables comparing two random sets of any nature if their quantitative description expressed in terms of the “best-fit” model is absent. Under the best-fit model, we imply the microscopic model that enables describing the measured data in terms of the minimal set of the fitting parameters. We propose at least two invariants: (a) the curve of the second order that coincides with the classical ellipse oriented at an arbitrary direction relative to the X- and Y-axes, and (b) the curve of the fourth order that has eight quantitative parameters and includes the cross-combination of the integer moments. In this paper, the DGIs of both types were used. These curves are made useful for the solution of a key problem in electrochemistry, i.e., the detection of small concentrations of d-tryptophan (6.54 ÷ 38.7) 10−5 mol·L−1 in a given solute (phosphate buffer solution (Na2HPO4 + KH2PO4) with pH = 6.86) that was activated by electrodes of two types—Pt (platinum) and C (carbon). The DGI method is free from treatment errors and model suppositions; therefore, it can be applied for the detection of small additives in a given solute and a further description can be attained with the help of a monotone/calibration curve expressed by means of parameters associated with the DGI.
Robust Planning of Energy and Environment Systems through Introducing Traffic Sector with Cost Minimization and Emissions Abatement under Multiple Uncertainties
Authors: Chen Cong , Zeng Xueting , Huang Guohe , Yu Lei , Li Yongping
Published: March 2019

Motor vehicles have been identified as a growing contributor to air pollution, such that analyzing the traffic policies on energy and environment systems (EES) has become a main concern for governments. This study developed a dual robust stochastic fuzzy optimization—energy and environmental systems (DRSFO-EES) model for sustainable planning EES, while considering the traffic sector through integrating two-stage stochastic programming, robust two-stage stochastic optimization, fuzzy possibilistic programming, and robust fuzzy possibilistic programming methods into a framework, which can be used to effectively tackle fuzzy and stochastic uncertainties as well as their combinations, capture the associated risks from fuzzy and stochastic uncertainties, and thoroughly analyze the trade-offs between system costs and reliability. The proposed model can: (i) generate robust optimized solutions for energy allocation, coking processing, oil refining, heat processing, electricity generation, electricity power expansion, electricity importation, energy production, as well as emission mitigation under multiple uncertainties; (ii) explore the impacts of different vehicle policies on vehicular emission mitigation; (iii) identify the study of regional atmospheric pollution contributions of different energy activities. The proposed DRSFO-EES model was applied to the EES of the Beijing-Tianjin-Hebei (BTH) region in China. Results generated from the proposed model disclose that: (i) limitation of the number of light-duty passenger vehicles and heavy-duty trucks can effectively reduce vehicular emissions; (ii) an electric cars’ policy is enhanced by increasing the ratio of its power generated from renewable sources; and (iii) the air-pollutant emissions in the BTH region are expected to peak around 2030, because the energy mix of the study region would be transformed from one dominated by coal to one with a cleaner pattern. The DRSFO-EES model can not only provide scientific support for the sustainable managing of EES by cost-effective ways, but also analyze the desired policies for mitigating pollutant emissions impacts with a risk adverse attitude under multiple uncertainties.
Wet Snow Flashover Characteristics of 500-kV AC Insulator Strings with Different Arrangements
Authors: Xu Jingwei , Yin Fanghui , Li Longji , Wen Qingfeng , Wang Hao , Liu Shunnan , Jia Zhidong , Farzaneh Masoud
Published: March 2019

In order to study the wet snow flashover characteristics of 500-kV AC insulator strings under different arrangements, wet snow flashover tests were carried out in the large climate chamber of China Electric Power Research Institute (CEPRI). The wet snow flashover voltages were obtained by the even-rising method and the flashovers were filmed by a camera. The test results showed that the installation of an anti-icing shed of large diameter could increase the wet snow flashover voltage. The distance between the two insulators was a key parameter that influenced the discharge process and the flashover voltage. Under Λ-string arrangement, for common insulators, the flashover performance of iced insulators increased with the connection angle; for anti-icing insulators, the flashover performance increased at first and then decreased with the connection angle. In wet snow conditions, when the connection angle was at the commonly adopted angle of 60°, the flashover performance of the common insulators under the V-string and Λ-string arrangements was almost the same. For anti-icing insulators, however, the V-string arrangement was recommended according to the tests. The results obtained in this study can provide a reference for external insulation design in wet snow conditions.
Laboratory Observations of Repeated Interactions between Ruptures and the Fault Bend Prior to the Overall Stick-Slip Instability Based on a Digital Image Correlation Method
Authors: Zhuo Yan-Qun , Guo Yanshuang , Bornyakov Sergei Alexandrovich
Published: March 2019

Fault geometry plays important roles in the evolution of earthquake ruptures. Experimental studies on the spatiotemporal evolution of the ruptures of a fault with geometric bands are important for understanding the effects of the fault bend on the seismogenic process. However, the spatial sampling of the traditional point contact type sensors is quite low, which is unable to observe the detailed spatiotemporal evolution of ruptures. In this study, we use a high-speed camera combined with a digital image correlation (DIC) method to observe ruptures during stick-slip motions of a simulated bent fault. Meanwhile, strain gages were also used to test the results of the DIC method. Multiple cycles of the alternative propagation of ruptures between the two fault segments on the both sides of the fault bend were observed prior to the overall failure of the fault. Moreover, the slip velocity and rupture speed were observed getting higher during this process. These results indicate the repeated interactions between the ruptures and the fault bend prior to the overall instability of the fault, which distinguishes the effect of the fault bend from the effect of asperities in straight faults on the evolution of ruptures. In addition, improvement in the temporal sampling rate of the DIC measurement system may further help to unveil the rupture evolution during the overall instability in future.
What We Do and What Is Done to Us: Teaching Art as Culture
Authors: Kenning Dean
Published: March 2019

Carl Andre’s opposition between an activating art and a pacifying culture becomes the impetus for wider reflections on artistic autonomy and agency with special reference to how fine art is taught at college. I propose that artistic agency might better be accounted for and enacted by conceiving of it not as something set against or at a distance from culture in general, but ‘as’ culture. Through an overview of various institutional and discursive accounts of artistic production which describe the ways in which art is itself influenced and determined by external factors, and an extended analysis of Raymond Williams theory of culture as ‘collective advance’, I propose that fine art education needs to confront the question of contemporary art’s wider cultural embeddedness, and the political culture of art itself—a politics based in the nature of the social relationships art practice engenders.
Electron-Induced Chemistry in the Condensed Phase
Authors: Bredehöft Jan Hendrik
Published: March 2019

Electron–molecule interactions have been studied for a long time. Most of these studies have in the past been limited to the gas phase. In the condensed-phase processes that have recently attracted attention from academia as well as industry, a theoretical understanding is mostly based on electron–molecule interaction data from these gas phase experiments. When transferring this knowledge to condensed-phase problems, where number densities are much higher and multi-body interactions are common, care must be taken to critically interpret data, in the light of this chemical environment. The paper presented here highlights three typical challenges, namely the shift of ionization energies, the difference in absolute cross-sections and branching ratios, and the occurrence of multi-body processes that can stabilize otherwise unstable intermediates. Examples from recent research in astrochemistry, where radiation driven chemistry is imminently important are used to illustrate these challenges.
Doily as Subgeometry of a Set of Nonunimodular Free Cyclic Submodules
Authors: Saniga Metod , Bartnicka Edyta
Published: March 2019

In this paper, it is shown that there exists a particular associative ring with unity of order 16 such that the relations between non-unimodular free cyclic submodules of its two-dimensional free left module can be expressed in terms of the structure of the generalized quadrangle of order two. Such a doily-centered geometric structure is surmised to be of relevance for quantum information.
Using Ramsey Theory to Measure Unavoidable Spurious Correlations in Big Data
Authors: Pawliuk Micheal , Waddell Michael Alexander
Published: March 2019

Given a dataset, we quantify the size of patterns that must always exist in the dataset. This is done formally through the lens of Ramsey theory of graphs, and a quantitative bound known as Goodman’s theorem. By combining statistical tools with Ramsey theory of graphs, we give a nuanced understanding of how far away a dataset is from correlated, and what qualifies as a meaningful pattern. This method is applicable to a wide range of datasets. As examples, we analyze two very different datasets. The first is a dataset of repeated voters ( n = 435 ) in the 1984 US congress, and we quantify how homogeneous a subset of congressional voters is. We also measure how transitive a subset of voters is. Statistical Ramsey theory is also used with global economic trading data ( n = 214 ) to provide evidence that global markets are quite transitive. While these datasets are small relative to Big Data, they illustrate the new applications we are proposing. We end with specific calls to strengthen the connections between Ramsey theory and statistical methods.
Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study
Authors: Protogerou Vassilis , Michalopoulos Efstathios , Mallis Panagiotis , Gontika Ioanna , Dimou Zetta , Liakouras Christos , Stavropoulos-Giokas Catherine , Kostakopoulos Nikolaos , Chrisofos Michael , Deliveliotis Charalampos
Published: March 2019

Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. This pilot study enrolled eight patients with diagnosed ED. Patients enrolled were suffering from organic ED due to diabetes melitus, hypertension, hypercholesterolaemia, and Peyronie disease. The patients were distributed in 2 groups. Patients in group A received adipose derived mesenchymal stem cells (ADMSC) resuspended in PL while patients in group B received only PL. ADMSCs were isolated from patients’ adipose tissue and expanded. In addition, blood sampling was obtained from the patients in order to isolate platelet lysate. After the application of the above treatments, patients were evaluated with an International Index of Erectile Function (IIEF-5) questionnaire, penile triplex, and reported morning erections. After MSCs and PL administration, patients presented improved erectile function after 1 and 3 months of follow-up. A statistically significant difference was observed in the IIEF-5 score before and after administration of both treatments after the first month (p < 0.05) and the third month (p < 0.05). No statistically significant difference was observed in the IIEF-5 score between group A and B patients. All patients were characterized by improved penile triplex and increased morning erections. No severe adverse reactions were observed in any patient except a minor pain at the site of injection, which was in the limits of tolerability. The results of this study indicated the satisfactory use of MSCs and PL in ED. MSCs in combination with PL or PL alone seems to be very promising, especially without having the negative effects of the current therapeutic treatment.
Quantifying Tubulin Concentration and Microtubule Number Throughout the Fission Yeast Cell Cycle
Authors: Loiodice Isabelle , Janson Marcel , Tavormina Penny , Schaub Sebastien , Bhatt Divya , Cochran Ryan , Czupryna Julie , Fu Chuanhai , Tran Phong
Published: March 2019

The fission yeast Schizosaccharomyces pombe serves as a good genetic model organism for the molecular dissection of the microtubule (MT) cytoskeleton. However, analysis of the number and distribution of individual MTs throughout the cell cycle, particularly during mitosis, in living cells is still lacking, making quantitative modelling imprecise. We use quantitative fluorescent imaging and analysis to measure the changes in tubulin concentration and MT number and distribution throughout the cell cycle at a single MT resolution in living cells. In the wild-type cell, both mother and daughter spindle pole body (SPB) nucleate a maximum of 23 ± 6 MTs at the onset of mitosis, which decreases to a minimum of 4 ± 1 MTs at spindle break down. Interphase MT bundles, astral MT bundles, and the post anaphase array (PAA) microtubules are composed primarily of 1 ± 1 individual MT along their lengths. We measure the cellular concentration of αβ-tubulin subunits to be ~5 µM throughout the cell cycle, of which one-third is in polymer form during interphase and one-quarter is in polymer form during mitosis. This analysis provides a definitive characterization of αβ-tubulin concentration and MT number and distribution in fission yeast and establishes a foundation for future quantitative comparison of mutants defective in MTs.
Dual Role of the Alternative Reading Frame ARF Protein in Cancer
Authors: Fontana Rosa , Ranieri Michela , La Mantia Girolama , Vivo Maria
Published: March 2019

The CDKN2a/ARF locus expresses two partially overlapping transcripts that encode two distinct proteins, namely p14ARF (p19Arf in mouse) and p16INK4a, which present no sequence identity. Initial data obtained in mice showed that both proteins are potent tumor suppressors. In line with a tumor-suppressive role, ARF-deficient mice develop lymphomas, sarcomas, and adenocarcinomas, with a median survival rate of one year of age. In humans, the importance of ARF inactivation in cancer is less clear whereas a more obvious role has been documented for p16INK4a. Indeed, many alterations in human tumors result in the elimination of the entire locus, while the majority of point mutations affect p16INK4a. Nevertheless, specific mutations of p14ARF have been described in different types of human cancers such as colorectal and gastric carcinomas, melanoma and glioblastoma. The activity of the tumor suppressor ARF has been shown to rely on both p53-dependent and independent functions. However, novel data collected in the last years has challenged the traditional and established role of this protein as a tumor suppressor. In particular, tumors retaining ARF expression evolve to metastatic and invasive phenotypes and in humans are associated with a poor prognosis. In this review, the recent evidence and the molecular mechanisms of a novel role played by ARF will be presented and discussed, both in pathological and physiological contexts.
Functional Segments on Intrinsically Disordered Regions in Disease-Related Proteins
Authors: Anbo Hiroto , Sato Masaya , Okoshi Atsushi , Fukuchi Satoshi
Published: March 2019

One of the unique characteristics of intrinsically disordered proteins (IPDs) is the existence of functional segments in intrinsically disordered regions (IDRs). A typical function of these segments is binding to partner molecules, such as proteins and DNAs. These segments play important roles in signaling pathways and transcriptional regulation. We conducted bioinformatics analysis to search these functional segments based on IDR predictions and database annotations. We found more than a thousand potential functional IDR segments in disease-related proteins. Large fractions of proteins related to cancers, congenital disorders, digestive system diseases, and reproductive system diseases have these functional IDRs. Some proteins in nervous system diseases have long functional segments in IDRs. The detailed analysis of some of these regions showed that the functional segments are located on experimentally verified IDRs. The proteins with functional IDR segments generally tend to come and go between the cytoplasm and the nucleus. Proteins involved in multiple diseases tend to have more protein-protein interactors, suggesting that hub proteins in the protein-protein interaction networks can have multiple impacts on human diseases.
Molecular Antioxidant Properties and In Vitro Cell Toxicity of the p-Aminobenzoic Acid (PABA) Functionalized Peptide Dendrimers §
Authors: Sowinska Marta , Morawiak Maja , Bochyńska-Czyż Marta , Lipkowski Andrzej W. , Ziemińska Elżbieta , Zabłocka Barbara , Urbanczyk-Lipkowska Zofia
Published: March 2019

Background: Exposure to ozone level and ultraviolet (UV) radiation is one of the major concerns in the context of public health. Numerous studies confirmed that abundant free radicals initiate undesired processes, e.g. carcinogenesis, cells degeneration, etc. Therefore, the design of redox-active molecules with novel structures, containing radical quenchers molecules with novel structures, and understanding their chemistry and biology, might be one of the prospective solutions. Methods: We designed a group of peptide dendrimers carrying multiple copies of p-aminobenzoic acid (PABA) and evaluated their molecular antioxidant properties in 1,1′-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) tests. Cytotoxicity against human melanoma and fibroblast cells as well as against primary cerebral granule cells (CGC) alone and challenged by neurotoxic sodium glutamate and production of reactive oxygen species (ROS) in presence of dendrimers were measured. Results: PABA-terminated dendrimers express enhanced radical and radical cation scavenging properties in relation to PABA alone. In cellular tests, the dendrimers at 100 μM fully suppress and between 20–100 μM reduce proliferation of the human melanoma cell line. In concentration 20 μM dendrimers generate small amount of the reactive oxygen species (<25%) but even in their presence human fibroblast and mouse cerebellar granule cells remain intact Moreover, dendrimers at 0.2–20 µM concentration (except one) increased the percentage of viable fibroblasts and CGC cells treated with 100 μM glutamate. Conclusions: Designed PABA-functionalized peptide dendrimers might be a potential source of new antioxidants with cationic and neutral radicals scavenging potency and/or new compounds with marked selectivity against human melanoma cell or glutamate-stressed CGC neurons. The scavenging level of dendrimers depends strongly on the chemical structure of dendrimer and the presence of other groups that may be prompted into radical form. The present studies found different biological properties for dendrimers constructed from the same chemical fragments but the differing structure of the dendrimer tree provides once again evidence that the structure of dendrimer can have a significant impact on drug–target interactions.
Electrochemical Biosensors as Potential Diagnostic Devices for Autoimmune Diseases
Authors: Florea Anca , Melinte Gheorghe , Simon Ioan , Cristea Cecilia
Published: March 2019

An important class of biosensors is immunosensors, affinity biosensors that are based on the specific interaction between antibodies and antigens. They are classified in four classes based on the type of employed transducer: electrochemical, optical, microgravimetric, and thermometric and depending on the type of recognition elements, antibodies, aptamers, microRNAs and recently peptides are integrating parts. Those analytical devices are able to detect peptides, antibodies and proteins in various sample matrices, without many steps of sample pretreatment. Their high sensitivity, low cost and the easy integration in point of care devices assuring portability are attracting features that justify the increasing interest in their development. The use of nanomaterials, simultaneous multianalyte detection and integration on platforms to form point-of-care devices are promising tools that can be used in clinical analysis for early diagnosis and therapy monitoring in several pathologies. Taking into account the growing incidence of autoimmune disease and the importance of early diagnosis, electrochemical biosensors could represent a viable alternative to currently used diagnosis methods. Some relevant examples of electrochemical assays for autoimmune disease diagnosis developed in the last several years based on antigens, antibodies and peptides as receptors were gathered and will be discussed further.
Experimental Research on Using Form-stable PCM-Integrated Cementitious Composite for Reducing Overheating in Buildings
Authors: Ramakrishnan Sayanthan , Sanjayan Jay , Wang Xiaoming
Published: March 2019

This paper investigates the potential of using form-stable phase change material (FS-PCM) integrated cement mortars in building envelopes to prevent overheating and to improve summer thermal comfort. The FS-PCM integrated cement mortar was applied as the interior surface plastering mortar of a full-scale test hut and compared with identical test huts built on cement plasterboard (OCB) and gypsum plasterboard (GPB). The test huts were exposed to outdoor climatic conditions, and indoor thermal behaviours were continuously monitored throughout the summer period. The effects of PCM in reducing the overheating was analysed by the intensity of thermal discomfort (ITDover) and frequency of thermal discomfort (FTDover) for overheating during the summer days. The comparison between different test huts showed that the application of PCM integrated cement mortars reduced the peak indoor temperature by up to 2.4 °C, compared to GPB and OCB test rooms. More importantly, the analysis of overheating effects revealed that at lower intensive thermal discomfort levels, FS-PCM largely reduces FTDover. As the intensity of thermal discomfort increases, the reduction in ITDover becomes dominant. At highly intensive thermal discomfort levels, the reduction was neither apparent in the intensity of thermal discomfort nor the period of discomfort.
Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy
Authors: Manzotti Gloria , Ciarrocchi Alessia , Sancisi Valentina
Published: March 2019

Histone DeACetylases (HDACs) are enzymes that remove acetyl groups from histones and other proteins, regulating the expression of target genes. Pharmacological inhibition of these enzymes re-shapes chromatin acetylation status, confusing boundaries between transcriptionally active and quiescent chromatin. This results in reinducing expression of silent genes while repressing highly transcribed genes. Bromodomain and Extraterminal domain (BET) proteins are readers of acetylated chromatin status and accumulate on transcriptionally active regulatory elements where they serve as scaffold for the building of transcription-promoting complexes. The expression of many well-known oncogenes relies on BET proteins function, indicating BET inhibition as a strategy to counteract their activity. BETi and HDACi share many common targets and affect similar cellular processes to the point that combined inhibition of both these classes of proteins is regarded as a strategy to improve the effectiveness of these drugs in cancer. In this work, we aim to discuss the molecular basis of the interplay between HDAC and BET proteins, pointing at chromatin acetylation as a crucial node of their functional interaction. We will also describe the state of the art of their dual inhibition in cancer therapy. Finally, starting from their mechanism of action we will provide a speculative perspective on how these drugs may be employed in combination with standard therapies to improve effectiveness and/or overcome resistance.
Immunotherapy Associated Pulmonary Toxicity: Biology Behind Clinical and Radiological Features
Authors: Porcu Michele , De Silva Pushpamali , Solinas Cinzia , Battaglia Angelo , Schena Marina , Scartozzi Mario , Bron Dominique , Suri Jasjit S. , Willard-Gallo Karen , Sangiolo Dario , Saba Luca
Published: March 2019

The broader use of immune checkpoint blockade in clinical routine challenges clinicians in the diagnosis and management of side effects which are caused by inflammation generated by the activation of the immune response. Nearly all organs can be affected by immune-related toxicities. However, the most frequently reported are: fatigue, rash, pruritus, diarrhea, nausea/vomiting, arthralgia, decreased appetite and abdominal pain. Although these adverse events are usually mild, reversible and not frequent, an early diagnosis is crucial. Immune-related pulmonary toxicity was most frequently observed in trials of lung cancer and of melanoma patients treated with the combination of the anti-cytotoxic T lymphocyte antigen (CTLA)-4 and the anti-programmed cell death-1 (PD-1) antibodies. The most frequent immune-related adverse event in the lung is represented by pneumonitis due to the development of infiltrates in the interstitium and in the alveoli. Clinical symptoms and radiological patterns are the key elements to be considered for an early diagnosis, rendering the differential diagnosis crucial. Diagnosis of immune-related pneumonitis may imply the temporary or definitive suspension of immunotherapy, along with the start of immuno-suppressive treatments. The aim of this work is to summarize the biological bases, clinical and radiological findings of lung toxicity under immune checkpoint blockade, underlining the importance of multidisciplinary teams for an optimal early diagnosis of this side effect, with the aim to reach an improved patient care.
Compositional and Functional Differences between Microbiota and Cervical Carcinogenesis as Identified by Shotgun Metagenomic Sequencing
Authors: Kwon Minji , Seo Sang-Soo , Kim Mi Kyung , Lee Dong Ock , Lim Myoung Cheol
Published: March 2019

Recent studies have reported the potential role of microbiomes in cervical disease. However, little is known about the microbiome composition and function in cervical carcinogenesis. We aimed to identify the compositional and functional alterations of cervical microbiomes in cases of cervical carcinogenesis of Korean women using shotgun metagenomic sequencing. In this study, using shotgun sequencing, we sequenced the cervical metagenomes of cervical intraneoplasia 2/3 (n = 17), cervical cancer (n = 12), and normal controls (n = 18) to identify the microbial abundances and enriched metabolic functions in cervical metagenomes. At the genus level, the microbiota of cervical cancer were differentially enriched with genera Alkaliphilus, Pseudothermotoga, and Wolbachia. Cervical intraepithelial neoplasia (CIN) 2/3 were enriched with Lactobacillus, Staphylococcus, and Candidatus Endolissoclinum. The normal group was enriched with Pseudoalteromonas and Psychrobacter. Further characterization of the functionalities of the metagenomes may suggest that six Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) that are involved in 10 pathways are associated with an increased risk of CIN2/3 and cervical cancer. Specifically, cervical metagenomes were enriched in the course of peptidoglycan synthesis and depleted by dioxin degradation and 4-oxalocrotonate tautomerase. The Cluster of Orthologous Groups (COG) category ‘Defense mechanisms’ was depleted in cervical cancer patients. Our findings based on shotgun metagenomic sequencing suggest that cervical microbiome community compositions and their metagenomics profiles differed between cervical lesions and normal subjects. Future studies should have larger sample sizes and/or aggregate their results to have sufficient power to detect reproducible and significant associations.
Advanced Rhodococcus Biocatalysts for Environmental Biotechnologies
Authors: Krivoruchko Anastasiia , Kuyukina Maria , Ivshina Irena
Published: March 2019

The review is devoted to biocatalysts based on actinobacteria of the genus Rhodococcus, which are promising for environmental biotechnologies. In the review, biotechnological advantages of Rhodococcus bacteria are evaluated, approaches used to develop robust and efficient biocatalysts are discussed, and their relevant applications are given. We focus on Rhodococcus cell immobilization in detail (methods of immobilization, criteria for strains and carriers, and optimization of process parameters) as the most efficient approach for stabilizing biocatalysts. It is shown that advanced Rhodococcus biocatalysts with improved working characteristics, enhanced stress tolerance, high catalytic activities, human and environment friendly, and commercially viable are developed, which are suitable for wastewater treatment, bioremediation, and biofuel production.
Licochalcone A Inhibits Cellular Motility by Suppressing E-cadherin and MAPK Signaling in Breast Cancer
Authors: Huang Wen-Chung , Su Haiso-Han , Fang Li-Wen , Wu Shu-Ju , Liou Chian-Jiun
Published: March 2019

A compound isolated from Glycyrrhiza uralensis, licochalcone A (LA) exhibits anti-inflammatory and anti-tumor properties in various cell lines. LA has been found to promote autophagy and suppress specificity protein 1, inducing apoptosis in breast cancer cells. However, the regulation of breast cancer cell invasion and migration by LA is elusive. Thus, the present study investigated whether LA induces apoptosis and cellular motility in MDA-MB-231 breast cells, and investigated the underlying molecular mechanisms. MDA-MB-231 cells treated with LA and cell viability measured by cell counting kit-8 assay. Apoptotic signal proteins checked by flow cytometry, fluorescent staining, and Western blot. LA effectively suppressed cell migration, and modulated E-cadherin and vimentin expression by blocking MAPK and AKT signaling. LA inhibited cell proliferation and cell cycle, modulated mitochondrial membrane potential and DNA damage, and reduced oxidative stress in MDA-MB-231 cells. LA also activated cleaved-caspase 3 and 9, significantly decreased Bcl-2 expression, ultimately causing the release of cytochrome c from the mitochondria into the cytoplasm. Overall, our findings suggest that LA decreases cell proliferation and increases reactive oxygen species production for induced apoptosis, and regulates E-cadherin and vimentin by reducing MAPK and AKT signaling, resulting in suppressed MDA-MB-231 cell migration and invasion.