bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of caries – protective effect of three recent dentin bonding agents, xeno v plus, tetric n bond ,one coat seven universal on demineralized root surface "- An in vitro study
Authors: Dugge Tanvi , Naik Balaram
Published: March 2019

Background and objectives: An area on the surface of tooth, apical to CEJ, where root caries are bound to occur undergoes clinically apparent dissolution of the calcified tissues. When dentin bonding agent is applied, it forms finger like resin tags protruding into patent dentin tubules When this resin penetrates the superficially demineralized collagen matrix, it forms a hybrid layerand prevents root surface lesions. Aim: To evaluate the caries protective effect of three recent DBAs on demineralized root surface. Materials and methods: 88 single rooted extracted human teeth were selected, root surfaces apical to CEJ were polished .Acid resistant nail paint wascoated over root surfaces exposing a rectangular window on the buccal surface. Three experimental groups made: Group 1 (XENO V PLUS), Group 2 (TETRIC N BOND), Group 3 (ONE COAT 7 UNIVERSAL). These groups were divided into 2 Subgroups (A and B). Adhesive was applied and light cured with air thinning. Over this second layer of adhesive was applied, light cured with /without air thinning. Each tooth samples were sliced. A light microscope was used to examine the caries like lesions.The statistical analysis was carried out. Results:All control group specimen showed lesions with a mean depth of 177.74μm. Subgroup B results were better than A and C. Summary and Conclusion: Demineralization on root surface can be impeded by DBA tested TetricN Bond which showed maximum cariesprotective effect Key words:Cementum, demineralization, dentine bonding agent
RISET EVALUASI PASAR KAGET DI KOTA BATAM
Authors: Purba Tiurniari
Published: March 2019

This study aims to determine what, who and how the shocked market in the Batam operate in accordance with research methodology used in research that is the method of evaluation research. The model used in this study is the CIPP evaluation, the model is analyzes the four dimensions of context dimension, input dimension, process dimension and product dimension. Batam city consists of 12 districts, there are only nine districts have 27 markets shocked. In this study, geographically dispersed market was dominated by Batu Aji sub-district with 10 markets in shock following Sekupang with five markets, while Sagulung four and Batam Kota had two shock markets. For District Nongsa, Batu Ampar, Bengkong, Sei Beduk, Lubuk Baja, each one market. The results of the evaluation obtained from this study is that the most needed by traders in the shock market is the attention and action of the local government. Attention in this regard is the support and proper facilities that can ultimately improve and develop the local economy concerned.
Husbandry Practices, Health, and Welfare Status of Organic Broilers in France
Authors: Souillard Rozenn , Répérant Jean-Michel , Experton Catherine , Huneau-Salaun Adeline , Coton Jenna , Balaine Loïc , Le Bouquin Sophie
Published: March 2019

Organic poultry production has increased sharply with growing consumer demand in the context of sustainable development. A study was conducted in 85 organic broiler flocks between 2014 and 2015 to describe the husbandry practices and the health and welfare status of organic broilers in France, and to study farming diversity by comparing independent farms (Ind farms, n = 15) with direct sales to farms working with companies (Comp farms, n = 70). Each flock was visited at 3 and 11 weeks of age to collect data on farming conditions, health disorders, and mortality. Welfare notation of 30 broilers per flock and parasitic examination of 5 broilers per flock was also performed. Findings showed significantly different farming management between Ind farms and Comp farms, with smaller flocks on the Ind farms (476 broilers/house vs. 3062 broilers/house, p < 0.01) more frequently in mobile houses. The mean mortality rate was 2.8%, mainly involving digestive disorders. Helminths were detected in 58.8% of the flocks. On average, 21.9% and 5.8% of broilers in a flock had footpad dermatitis and dirty feathers, respectively. The health and welfare characteristics of organic broilers on Ind farms vs. Comp farms were not significantly different, except dirtier feathers and more footpad dermatitis on Ind farms (19.1% vs. 2.9%, p = 0.03 and 39.6% vs. 18.1%, p = 0.02, respectively), associated with poultry housing conditions in mobile houses (p < 0.01). This study provides greater insight into farming sustainability aspects related to the husbandry practices, and the health and welfare of organic broilers in France.
Replacement of Fish Meal by Defatted Yellow Mealworm (Tenebrio molitor) Larvae in Diet Improves Growth Performance and Disease Resistance in Red Seabream (Pargus major)
Authors: Ido Atsushi , Hashizume Atsushi , Ohta Takashi , Takahashi Takayuki , Miura Chiemi , Miura Takeshi
Published: March 2019

Yellow mealworm (Tenebrio molitor) larvae are a potential alternative animal protein source for sustainable aquaculture. However, reports on the successful complete substitution of fish meal with yellow mealworm larvae in an aquaculture diet have been limited. In this study, we conducted a feeding trial with red seabream (Pagrus major) being fed diets with partial or complete replacement of fish meal with yellow mealworm larvae defatted with a hexane–ethanol solution. Feed intake in red seabream increased in accordance with yellow mealworm larvae inclusion, and diets including 65% defatted mealworm larvae (complete replacement of fish meal) showed significant growth promotion. The addition of the oil fraction from mealworm larvae to diets resulted in growth reduction, despite meeting the nutritional requirements of red seabream. Moreover, the survival rate of red seabreams fed diets with partial replacement of fish meal with mealworm larvae was significantly higher in a challenge test with pathogenic Edwardsiella tarda bacteria. The present study demonstrated that yellow mealworm larvae are not merely an alternative animal protein, but have potential as functional feed ingredients for aquaculture production.
Effect of Different Environment Enrichments on Behaviour and Social Interactions in Growing Pigs
Authors: Giuliotti Lorella , Benvenuti Maria Novella , Giannarelli Alessandro , Mariti Chiara , Gazzano Angelo
Published: March 2019

(1) Background: Pigs are active animals that require a suitable environment to be able to express their exploratory behaviour. The aim of the present study was to compare the effects of different environmental enrichments on the behaviour, social interactions, salivary cortisol concentration and body weight of pigs during the growing phase. (2) Methods: The investigation involved 75 pigs divided into three groups. The environmental enrichments were arranged as follows: Hanging metal chains for the control group; hanging metal chains and hanging logs for the second group; hanging metal chains and logs laying on the floor for the third group. Each group was video recorded twice a week for six weeks. The scan sampling technique was used. Salivary cortisol and live body weight were also recorded regularly. Parametric (ANOVA) and non-parametric statistics were used to analyse the data. (3) Results: Hanging logs were found to be more effective than logs laying on the floor at reducing aggression within the group tested, resulting in a more comfortable environment. Salivary cortisol concentration and growth did not show significant differences between the three groups. (4) Conclusions: The use of hanging logs affected some interactive patterns that resulted in decreasing the aggressive episodes of pigs, thereby providing a more comfortable environment.
Direct Yaw Moment Control for Enhancing Handling Quality of Lightweight Electric Vehicles with Large Load-To-Curb Weight Ratio
Authors: Raksincharoensak Pongsathorn , Daisuke Sato , Lidberg Mathias
Published: March 2019

In this paper a vehicle dynamics control system is designed to compensate the change in vehicle handling dynamics of lightweight vehicles due to variation in loading conditions and the effectiveness of the proposed design is verified by simulations and an experimental study using a fixed-base driving simulator. Considering the electrification of future mobility, the target vehicle of this research is a lightweight vehicle equipped with in-wheel motors that can generate an additional direct yaw moment by transverse distribution of traction forces to control vehicle yawing as well as side slip motions. Previously, the change in vehicle handling dynamics for various loading conditions have been analyzed by using a linear two-wheel vehicle model in planar motion and a control law of the DYC system based on feed-forward of front steering angular velocity and feedback of vehicle yaw rate. The feed-forward controller is derived based on the model following control with approximation of the vehicle dynamics to 1st-order transfer function. To make the determination of the yaw rate feedback gain model-based and adaptable to various vehicle velocity conditions, this paper selects a method where the yaw rate feedback gain in the DYC system is determined in a way that the steady-state yaw rate gain of the controlled loaded vehicle matches the gain of the unloaded vehicle. The DYC system is simulated in a single lane change maneuver to confirm the improved responsiveness of the vehicle while simulations of a double-lane change maneuver with a driver steering model confirms the effectiveness of the DYC system to support tracking control. Finally, the effectiveness of the proposed DYC system is also verified in an experimental study with ten human drivers using a fix-based driving simulator.
Two-Dimensional Modeling of Pressure Swing Adsorption (PSA) Oxygen Generation with Radial-Flow Adsorber
Authors: Yang Xiong , Wang Haoyu , Chen Jiangwei , Li Ziyi , Liu Yingshu , Zhang Chuanzhao , Xing Yi
Published: March 2019

Radial flow is an important type of flow direction for large-scale pressure swing adsorption (PSA) oxygen generation systems. In this study, a numerical simulation of a PSA oxygen generation process based on radial-flow adsorbers was performed with two-dimensional CFD modeling. The gas distribution, the maldistribution factor and the pressure difference were comparatively investigated at each flow type of the radial-flow adsorber. Considering the gas adsorption performance, the results indicated that the centripetal π-flow radial adsorber has the best flow characteristics for the PSA process. The oxygen purity distribution within the adsorption bed was studied to compare centripetal and centrifugal π-flows, and the former was shown to perform better on oxygen enrichment and adsorbent desorption. The steady state was achieved after eight cycles for the centripetal-π adsorber and each of the four steps of the PSA process was explored in detail to show the advantageous properties for oxygen generation in terms of adsorption and desorption. The relationships between the product flow rate and the oxygen purity and recovery were further investigated.
Electrochemical Removal of Chromium (VI) from Wastewater
Authors: Peng Hao , Leng Yumeng , Guo Jing
Published: March 2019

The removal of hexavalent chromium has attracted much attention as it is a hazardous contaminant. Electrochemical reduction technology was applied to remove chromium (VI) from wastewater. The mechanisms and parameters that affect the reduction process were investigated. The results showed that the reduction efficiency was significantly affected by the concentration of H2SO4, current density, and reaction temperature. The reduction efficiency was up to 86.45% at an H2SO4 concentration of 100 g/L, reaction temperature of 70 °C, current density at 50 A/m2, reaction time at 180 min, and stirring rate of 500 rpm. The reduction process of chromium (VI) followed a pseudo-first-order equation, and the reduction rate constant could be expressed as Kobs = k [H2SO4]1·[j]4·exp−4170/RT.
Fault Diagnosis of Rolling Bearings Based on Improved Kurtogram in Varying Speed Conditions
Authors: Ren Yong , Li Wei , Zhang Bo , Zhu Zhencai , Jiang Fang
Published: March 2019

Envelope analysis is a widely used method in fault diagnoses of rolling bearings. An optimal narrowband chosen for the envelope demodulation is critical to obtain high detection accuracy. To select the narrowband, the fast kurtogram (FK), which computes the kurtosis of a set of filtered signals, is introduced to detect cyclic transients in a signal, and the zone with the maximum kurtosis is the optimal frequency band. However, the kurtosis value is affected by rotating frequencies and is sensitive to large random impulses which normally occur in industrial applications. These factors weaken the performance of the FK for extracting weak fault features. To overcome these limitations, a novel feature named Order Spectrum Correlated Kurtosis (OSCK) is proposed, replacing the kurtosis index in the FK, to construct an improved kurtogram called Fast Order Spectrum Correlated Kurtogram (FOSCK). A band-pass filter is used to extract the optimal frequency band signal corresponding to the maximum OSCK. The envelope of the filtered signal is calculated using the Hilbert transform, and a low-pass filter is employed to eliminate the trend terms of the envelope. Then, the non-stationary filtered envelope is converted in the time domain into the stationary envelope in the angular domain via Computed Order Tracking (COT) to remove the effects of the speed fluctuation. The order structure of the angular domain envelope signal can then be used to determine the type of fault by identifying its characteristic order. This method offers several merits, such as fine order spectrum resolution and robustness to both random shock and heavy noise. Additionally, it can accurately locate the bearing fault resonance band within a relatively large speed fluctuation. The effectiveness of the proposed method is verified by a number of simulations and experimental bearing fault signals. The results are compared with several existing methods; the proposed method outperforms others in accurate bearing fault feature extraction under varying speed conditions.
Review of Coal-Fired Electrification and Magnetic Separation Desulfurization Technology
Authors: Chen Yan , Cao Min , Ma Chunyan
Published: March 2019

This paper briefly introduces various methods of coal desulfurization (physical desulphurization, chemical desulfurization, biological desulfurization, etc.) and analyzes some problems existing in each method. The principle and research process of friction electrostatic separation technology and high gradient magnetic separation technology in pre-combustion desulfurization technology are emphatically introduced, and the development trend of coal-fired desulfurization technology in the future is prospected.
Altitudinal Shift of Tetrao urogallus in an Alpine Natura 2000 Site: Implications for Habitat Restoration
Authors: Sitzia Tommaso , Campagnaro Thomas , Dainese Matteo , Dallabrida Francesco , Mattedi Silvano Mario , Portaccio Alessia
Published: March 2019

Capercaillie (Tetrao urogallus L.), a territorial galliform species, is known to prefer mature conifer stands with canopy gaps and a vigorous understory of ericaceous species. Capercaillie is a useful umbrella species that has recently shown declining population trends and distribution changes in its southern geographic range. We aim to identify and assess the possible changes in summer capercaillie habitat selection between 2001 and 2011 in the Scanuppia Natura 2000 site (south-eastern Alps). The area is dominated by spruce (Picea abies (L.) Karsten) forests, followed by mixed forests, scrub, and open habitats. In both years, summer presence–absence of capercaillie was verified through the detection of droppings over 10 m radius circular plots located along contour lines (1500–1800 m). A set of environmental and habitat features was also surveyed. While overall population numbers remain unchanged over the surveyed period, results have shown an altitudinal shift in capercaillie distribution. Habitat variables had a stronger effect on the presence of capercaillie in 2001 than in 2011. Land cover and climate change are likely among the drivers of the shift in altitudinal distribution. This confirms the relevance of habitat restoration actions and to monitor changes in factors explaining capercaillie habitat selection.
A Review of Super-Resolution Imaging through Optical High-Order Interference [Invited]
Authors: Hong Peilong , Zhang Guoquan
Published: March 2019

Resolution is crucially important for optical imaging, which defines the smallest spatial feature of object that can be delivered by light wave. However, due to the wave nature of light, optical imaging is of limited resolution, widely known as Rayleigh limit or Abbe limit. Nevertheless, this limit can be overcome by considering the loopholes in the derivation of the Rayleigh limit, such as light–matter interaction, structured illumination, and near-field interference. In contrast to the conventional single-photon interference, multi-photon amplitudes responsible for optical high-order interference could be designed to possess a reduced effective wavelength, enabling the breakthrough of the Rayleigh limit. In this review, we will present recently developed super-resolution imaging schemes based on optical high-order interference, and discuss future perspectives.
Highly Sensitive and Selective H2S Chemical Sensor Based on ZnO Nanomaterial
Authors: Galstyan Vardan , Poli Nicola , Comini Elisabetta
Published: March 2019

ZnO is worth evaluating for chemical sensing due to its outstanding physical and chemical properties. We report the fabrication and study of the gas sensing properties of ZnO nanomaterial for the detection of hydrogen sulfide (H2S). This prepared material exhibited a 7400 gas sensing response when exposed to 30 ppm of H2S in air. In addition, the structure showed a high selectivity towards H2S against other reducing gases. The high sensing performance of the structure was attributed to its nanoscale size, morphology and the disparity in the sensing mechanism between the H2S and other reducing gases. We suggest that the work reported here including the simplicity of device fabrication is a significant step toward the application of ZnO nanomaterials in chemical gas sensing systems for the real-time detection of H2S.
Recent Developments in the Field of the Metal-Insulator Transition in Two Dimensions
Authors: Shashkin Alexander A. , Kravchenko Sergey V.
Published: March 2019

We review the latest developments in the field of the metal-insulator transition in strongly-correlated two-dimensional electron systems. Particular attention is given to recent discoveries of a sliding quantum electron solid and interaction-induced spectrum flattening at the Fermi level in high-quality silicon-based structures.
Physics Parameterization Selection in RCM and ESM Simulations Revisited: New Supporting Approach Based on Empirical Copulas
Authors: Laux Patrick , Kerandi Noah , Kunstmann Harald
Published: March 2019

This study aims at a new supplementary approach to identify optimal configurations of physics parameterizations in regional climate models (RCMs) and earth system models (ESMs). Traditional approaches separately evaluate variable performance, which may lead to an inappropriate selection of physics parameterization combinations. Besides traditional approaches, we suggest an additional selection approach by considering the joint dependence structure (covariance structure) between key meteorological variables, i.e., precipitation P and temperature T. This is accomplished by empirical P and T copula functions and the χ 2 -test, and is demonstrated in two locations in Kenya with different major precipitation processes. It is shown that the selection based on traditional approaches alone may lead to nonoptimal decisions in terms of joint dependence structure between P and T. It was found that the copula-based approach may reduce the need for complex multivariate bias correction, as demonstrated using local intensity scaling for P and linear scaling for T. The new approach may contribute to improving RCM and ESM simulations and climate-impact studies worldwide.
Nanostructured Materials for Food Applications: Spectroscopy, Microscopy and Physical Properties
Authors: Sharma Shubham , Jaiswal Swarna , Duffy Brendan , Jaiswal Amit K.
Published: March 2019

Nanotechnology deals with matter of atomic or molecular scale. Other factors that define the character of a nanoparticle are its physical and chemical properties, such as surface area, surface charge, hydrophobicity of the surface, thermal stability of the nanoparticle and its antimicrobial activity. A nanoparticle is usually characterized by using microscopic and spectroscopic techniques. Microscopic techniques are used to characterise the size, shape and location of the nanoparticle by producing an image of the individual nanoparticle. Several techniques, such as scanning electron microscopy (SEM), transmission electron microscopy/high resolution transmission electron microscopy (TEM/HRTEM), atomic force microscopy (AFM) and scanning tunnelling microscopy (STM) have been developed to observe and characterise the surface and structural properties of nanostructured material. Spectroscopic techniques are used to study the interaction of a nanoparticle with electromagnetic radiations as the function of wavelength, such as Raman spectroscopy, UV–Visible spectroscopy, attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), dynamic light scattering spectroscopy (DLS), Zeta potential spectroscopy, X-ray photoelectron spectroscopy (XPS) and X-ray photon correlation spectroscopy. Nanostructured materials have a wide application in the food industry as nanofood, nano-encapsulated probiotics, edible nano-coatings and in active and smart packaging.
Effect of Antifreeze Glycoproteins on Organoid Survival during and after Hypothermic Storage
Authors: Huelsz-Prince Guizela , DeVries Arthur L. , Bakker Huib J. , van Zon Jeroen S. , Meister Konrad
Published: March 2019

We study the effect of antifreeze glycoproteins (AFGPs) on the survival of organoids under hypothermic conditions. We find that the survival of organoids in cold conditions depends on their developmental stage. Mature organoids die within 24 h when being stored at 4 °C, while cystic organoids can survive up to 48 h. We find that in the presence of AFGPs, the organoid survival is prolonged up to 72 h, irrespective of their developmental stage. Fluorescence microscopy experiments reveal that the AFGPs predominately localize at the cell surface and cover the cell membranes. Our findings support a mechanism in which the positive effect of AFGPs on cell survival during hypothermic storage involves the direct interaction of AFGPs with the cell membrane. Our research highlights organoids as an attractive multicellular model system for studying the action of AFGPs that bridges the gap between single-cell and whole-organ studies.
Calcium Carbonate Nanoparticles Can Activate the Epithelial–Mesenchymal Transition in an Experimental Gastric Cancer Model
Authors: Senchukova Marina , Tomchuk Olesya , Shurygina Elena , Letuta Sergey , Alidzhanov Eskender , Nikiyan Hike , Razdobreev Dmitry
Published: March 2019

Previously, we have shown the possibility of intramucosal gastric carcinoma induction by the intragastric administration of a mixture of formaldehyde and hydrogen peroxide in rats. In this study, we report a sizable increase in carcinogenic properties of the mixture when a suspension containing calcium carbonate nanoparticles was added to it. This technique allowed us to reduce both the number of the carcinogen administrations from twelve to two and the time to the cancer induction from six to four months. Although the induced tumors were represented by the intramucosal carcinomas, they were characterized by the extensive invasion of individual tumor cells and their clusters into the muscle layer and serosa as well as into the omentum and blood vessels. Considering that the invasive tumor cells were positive for vimentin, Snail and TGF-β2, we concluded that their invasion was the result of the activation of epithelial–mesenchymal transition (EMT) mechanisms. Thus, taking into account the data obtained, it can be assumed that under the conditions of inflammation or carcinogenesis, the calcium carbonate nanoparticles may affect the activation of EMT mechanisms.
Assessment and Impact of Cognitive Impairment in Multiple Sclerosis: An Overview
Authors: Macías Islas Miguel Ángel , Ciampi Ethel
Published: March 2019

Cognitive impairment affects 40–60% of patients with multiple sclerosis. It may be present early in the course of the disease and has an impact on a patient’s employability, social interactions, and quality of life. In the last three decades, an increasing interest in diagnosis and management of cognitive impairment has arisen. Neuropsychological assessment and neuroimaging studies focusing on cognitive impairment are now being incorporated as primary outcomes in clinical trials. However, there are still key uncertainties concerning the underlying mechanisms of damage, neural basis, sensitivity and validity of neuropsychological tests, and efficacy of pharmacological and non-pharmacological interventions. The present article aimed to present an overview of the assessment, neural correlates, and impact of cognitive impairment in multiple sclerosis.
Leadership and Motivational Climate: The Relationship with Objectives, Commitment, and Satisfaction in Base Soccer Players
Authors: Calvo Concepción , Topa Gabriela
Published: March 2019

The objective of the present study is to analyze non-professional soccer players’ preferences regarding coach leadership style and motivational climate and to determine the relationship of these variables with players’ satisfaction, sport commitment, and sport objectives. The participants were 151 players, aged between 10 and 24 years, divided into five categories: Alevín, Infantil, Cadet, Feminine, and Juvenile, all belonging to the Aragonese Soccer Federation. The participants completed questionnaires assessing their perception of their coach’s leadership style, the team’s motivational climate, their individual satisfaction, degree of sport commitment, and sport objectives. The results show that the leadership styles of training and instruction (M = 3.98, SD = 0.43) and positive feedback (M = 4.02, SD = 0.53) are the most valued by the players in all categories. The training and instruction leadership style had the highest correlations with task-oriented motivational climate (r = 0.40). The findings of the regression analysis show that a training and instruction leadership style and a task-oriented motivational climate significantly predict players’ satisfaction (13.3%) and sport commitment (14.5%).
Contribution of Anoctamins to Cell Survival and Cell Death
Authors: Kunzelmann Karl , Ousingsawat Jiraporn , Benedetto Roberta , Cabrita Ines , Schreiber Rainer
Published: March 2019

Before anoctamins (TMEM16 proteins) were identified as a family of Ca2+-activated chloride channels and phospholipid scramblases, the founding member anoctamin 1 (ANO1, TMEM16A) was known as DOG1, a marker protein for gastrointestinal stromal tumors (GIST). Meanwhile, ANO1 has been examined in more detail, and the role of ANO1 in cell proliferation and the development of different types of malignomas is now well established. While ANO5, ANO7, and ANO9 may also be relevant for growth of cancers, evidence has been provided for a role of ANO6 (TMEM16F) in regulated cell death. The cellular mechanisms by which anoctamins control cell proliferation and cell death, respectively, are just emerging; however, the pronounced effects of anoctamins on intracellular Ca2+ levels are likely to play a significant role. Recent results suggest that some anoctamins control membrane exocytosis by setting Ca2+i levels near the plasma membrane, and/or by controlling the intracellular Cl− concentration. Exocytosis and increased membrane trafficking induced by ANO1 and ANO6 may enhance membrane expression of other chloride channels, such as CFTR and volume activated chloride channels (VRAC). Notably, ANO6-induced phospholipid scrambling with exposure of phosphatidylserine is pivotal for the sheddase function of disintegrin and metalloproteinase (ADAM). This may support cell death and tumorigenic activity of IL-6 by inducing IL-6 trans-signaling. The reported anticancer effects of the anthelminthic drug niclosamide are probably related to the potent inhibitory effect on ANO1, apart from inducing cell cycle arrest through the Let-7d/CDC34 axis. On the contrary, pronounced activation of ANO6 due to a large increase in intracellular calcium, activation of phospholipase A2 or lipid peroxidation, can lead to ferroptotic death of cancer cells. It therefore appears reasonable to search for both inhibitors and potent activators of TMEM16 in order to interfere with cancer growth and metastasis.
Clinical Management of Blood–Brain Barrier Disruptions after Active Raster-Scanned Carbon Ion Re-Radiotherapy in Patients with Recurrent Head-and-Neck Cancer
Authors: Held Thomas , Akbaba Sati , Lang Kristin , Harrabi Semi , Bernhardt Denise , Freudlsperger Christian , Kargus Steffen , Plinkert Peter , Rieken Stefan , Herfarth Klaus , Debus Jürgen , Adeberg Sebastian
Published: March 2019

Purpose: The aim of the current evaluation was to assess central nervous system necrosis (CNSN) after re-irradiation with carbon ions (CR) in two-hundred seventeen (n = 217) patients with recurrent head-and-neck cancer (HNC). Methods: Thirty-six (n = 36) patients with CNSN were assessed retrospectively regarding clinical symptoms and radiographic response. Results: CNSN were classified according to clinical management in line with the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. At a median follow-up of 25.3 months (range 3.3–79.9 months), the median time interval until occurrence of grade I, II, and III CNSN was 9.2 months (range 2.8–75.0 months), 10.2 months (range 2.3–60.5 months), and 16.6 months (range 8.7–32.5 months), respectively. In one patient with an adenocarcinoma infiltrating the frontal lobe, an extensive CNSN grade IV was suspected but the patient declined surgical intervention. Radiographic response after treatment of CNSN grade I, II, and III, defined as ≥25% reduction of the T2 alteration on Magnetic Resonance Imaging (MRI), was observed in 4 (16.0%), 5 (29.4%), and 4 (80%) patients, respectively. Conclusion: CNSN occurred late and frequent after re-irradiation with carbon ions in patients with HNC infiltrating the base of skull. The clinical outcome with adequate treatment was encouraging but correct diagnosis of CNSN remains challenging.
Perilipin 5 and Lipocalin 2 Expression in Hepatocellular Carcinoma
Authors: Asimakopoulou Anastasia , Vucur Mihael , Luedde Tom , Schneiders Silvia , Kalampoka Stavroula , Weiss Thomas S. , Weiskirchen Ralf
Published: March 2019

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers worldwide. Therefore, current global research focuses on molecular tools for early diagnosis of HCC, which can lead to effective treatment at an early stage. Perilipin 5 (PLIN5) has been studied as one of the main proteins of the perilipin family, whose role is to maintain lipid homeostasis by inhibiting lipolysis. In this study, we show for the first time that PLIN5 is strongly expressed in tumors of human patients with HCC as well as in mouse livers, in which HCC was genetically or experimentally induced by treatment with the genotoxic agent diethylnitrosamine. Moreover, the secreted acute phase glycoprotein Lipocalin 2 (LCN2) established as a biomarker of acute kidney injury, is also proven to indicate liver injury with upregulated expression in numerous cases of hepatic damage, including steatohepatitis. LCN2 has been studied in various cancers, and it has been assigned roles in multiple cellular processes such as the suppression of the invasion of HCC cells and their metastatic abilities. The presence of this protein in blood and urine, in combination with the presence of α -Fetoprotein (AFP), is hypothesized to serve as a biomarker of early stages of HCC. In the current study, we show in humans and mice that LCN2 is secreted into the serum from liver cancer tissue. We also show that AFP-positive hepatocytes represent the main source for the massive expression of LCN2 in tumoral tissue. Thus, the strong presence of PLIN5 and LCN2 in HCC and understanding their roles could establish them as markers for diagnosis or as treatment targets against HCC.
Immunohistochemical Expression of Autophagy-Related Proteins in Advanced Tubular Gastric Adenocarcinomas and Its Implications
Authors: Ieni Antonio , Cardia Roberta , Giuffrè Giuseppe , Rigoli Luciana , Caruso Rosario Alberto , Tuccari Giovanni
Published: March 2019

In neoplastic conditions, autophagy may act as a tumor suppressor avoiding the accumulation of damaged proteins and organelles or as a mechanism of cell survival promoting the tumor growth. Although ultrastructural analysis has been considered the traditional method to identify autophagy, some proteins such as microtubule-associated protein 1 light chain 3 (LC3A/B), Beclin-1 and activating molecule in Beclin-1-regulated autophagy protein-1 (AMBRA-1) may be considered as markers of autophagy-assisted cancerogenesis. Herein, we analyzed a cohort of advanced tubular gastric adenocarcinomas by the abovementioned immunohistochemical antisera; through immunohistochemistry, autophagy (A-IHC) is diagnosed when at least two out of the three proteins are positive in the samples. Immunostaining for LC3A/B, Beclin-1, and AMBRA-1 was exclusively found in neoplastic elements, but not in surrounding stromal cells. In detail, LC3A/B and Beclin 1 were expressed both in the cytoplasm and in the nucleus of the cancer cells, while AMBRA-1 was preferentially localized in the nucleus, mainly in high grade cases. LC3A/B, Beclin 1, and AMBRA-1 expression were positive in 18 (56.2%), 17 (53.1%), and 12 (37.5%) cases, respectively. The sensibility and specificity of LC3A/B and Beclin-1 ranged from 81.25% to 93.75%, with high efficiency (90.63%) for Beclin-1. Moreover, the ultrastructural autophagic index (AI) was also available in all cases. All high-grade cases documented a Ki-67 labelling index (LI) ≥ 30%, even if three low-grade cases revealed a high Ki-67 value; p53 positivity was encountered in 21/32 (65.62%) of cases, independently of the tumor grade. A statistically significant correlation among A-IHC and clinicopathological parameters such as grade, stage, clinical course, Ki-67 LI and AI was revealed. Univariate analysis documented a significant p-value for the same autophagic variables. Additionally, multivariate survival analysis identified the grade, AI and A-IHC as independent significant variables. Finally, the overall survival curves of all cases of gastric tubular adenocarcinoma were greatly dependent on A-IHC. Therefore, we suggest that autophagic-related proteins might be considered promising predictive prognostic factors of advanced gastric cancer. Further investigations may be required to determine whether new targeted therapies should be addressed to autophagy-related proteins.
Review on the Macro-Transport Processes Theory for Irregular Pores able to Perform Catalytic Reactions
Authors: Santamaría-Holek Iván , Hernández Saúl , García-Alcántara Consuelo , Ledesma-Durán Aldo
Published: March 2019

We review and generalize a recent theoretical framework that provides a sound physicochemical basis to describe how volume and surface diffusion are affected by adsorption and desorption processes, as well as by catalytic conversion within the space defined by the irregular geometry of the pores in a material. The theory is based on two single-dimensional mass conservation equations for irregular domains deduced for the volumetric (bulk) and surface mass concentrations. It offers a powerful tool for analyzing and modeling mass transport across porous media like zeolites or artificially build materials, since it establishes how the microscopic quantities that refer to the internal details of the geometry, the flow and the interactions within the irregular pore can be translated into macroscopic variables that are currently measured in experiments. The use of the theory in mass uptake experiments is explained in terms of breakthrough curves and effective mass diffusion coefficients which are explicitly related to the internal geometry of the pores.
Highly Dispersed Ni Nanocatalysts Derived from NiMnAl-Hydrotalcites as High-Performing Catalyst for Low-Temperature Syngas Methanation
Authors: Lu Bin , Zhuang Jiahao , Du Jinping , Gu Fangna , Xu Guangwen , Zhong Ziyi , Liu Qing , Su Fabing
Published: March 2019

Increasing the low-temperature performance of nickel-based catalysts in syngas methanation is critical but very challenging, because at low temperatures there is high concentration of CO on the catalyst surface, causing formation of nickel carbonyl with metallic Ni and further catalyst deactivation. Herein, we have prepared highly dispersed Ni nanocatalysts by in situ reduction of NiMnAl-layered double hydroxides (NiMnAl-LDHs) and applied them to syngas methanation. The synthesized Ni nanocatalysts maintained the nanosheet structure of the LDHs, in which Ni particles were decorated with MnOy species and embedded in the AlOx nanosheets. It was observed that the Ni nanocatalysts exhibited markedly better low-temperature performance than commercial catalysts in the syngas methanation. At 250 °C, 3.0 MPa and a high weight hourly space velocity (WHSV) of 30,000 mL·g−1·h−1, both the CO conversion and the CH4 selectivity reached 100% over the former, while those over the commercial catalyst were only 14% and 76%, respectively. Furthermore, this NiMnAl catalyst exhibited strong anti-carbon and anti-sintering properties at high temperatures. The enhanced low-temperature performance and high-temperature stability originated from the promotion effect of MnOy and the embedding effect of AlOx in the catalyst.
Reproductive Strategy Inferred from Major Histocompatibility Complex-Based Inter-Individual, Sperm-Egg, and Mother-Fetus Recognitions in Giant Pandas (Ailuropoda melanoleuca)
Authors: Zhu Ying , Wan Qiu-Hong , Zhang He-Min , Fang Sheng-Guo
Published: March 2019

Few major histocompatibility complex (MHC)-based mate choice studies include all MHC genes at the inter-individual, sperm-egg, and mother-fetus recognition levels. We tested three hypotheses of female mate choice in a 17-year study of the giant panda (Ailuropoda melanoleuca) while using ten functional MHC loci (four MHC class I loci: Aime-C, Aime-F, Aime-I, and Aime-L; six MHC class II loci: Aime-DRA, Aime-DRB3, Aime-DQA1, Aime-DQA2, Aime-DQB1, and Aime-DQB2); five super haplotypes (SuHa, SuHaI, SuHaII, DQ, and DR); and, seven microsatellites. We found female choice for heterozygosity at Aime-C, Aime-I, and DQ and for disassortative mate choice at Aime-C, DQ, and DR at the inter-individual recognition level. High mating success occurred in MHC-dissimilar mating pairs. No significant results were found based on any microsatellite parameters, suggesting that MHCs were the mate choice target and there were no signs of inbreeding avoidance. Our results indicate Aime-DQA1- and Aime-DQA2-associated disassortative selection at the sperm-egg recognition level and a possible Aime-C- and Aime-I-associated assortative maternal immune tolerance mechanism. The MHC genes were of differential importance at the different recognition levels, so all of the functional MHC genes should be included when studying MHC-dependent reproductive mechanisms.
Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation
Authors: Silachev Denis , Goryunov Kirill , Shpilyuk Margarita , Beznoschenko Olga , Morozova Natalya , Kraevaya Elizaveta , Popkov Vasily , Pevzner Irina , Zorova Ljubava , Evtushenko Ekaterina , Starodubtseva Natalia , Kononikhin Alexey , Bugrova Anna , Evtushenko Evgeniy , Plotnikov Egor , Zorov Dmitry , Sukhikh Gennady
Published: March 2019

Mesenchymal stem cells (MSCs) have emerged as a potent therapeutic tool for the treatment of a number of pathologies, including immune pathologies. However, unwelcome effects of MSCs on blood coagulation have been reported, motivating us to explore the thrombotic properties of human MSCs from the umbilical cord. We revealed strong procoagulant effects of MSCs on human blood and platelet-free plasma using rotational thromboelastometry and thrombodynamic tests. A similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EVs). To offer approaches to avoid unwanted effects, we studied the impact of a heparin supplement on MSC procoagulative properties. However, MSCs still retained procoagulant activity toward blood from children receiving a therapeutic dose of unfractionated heparin. An analysis of the mechanisms responsible for the procoagulant effect of MSCs/EVs revealed the presence of tissue factor and other proteins involved in coagulation-associated pathways. Also, we found that some MSCs and EVs were positive for annexin V, which implies the presence of phosphatidylserine on their surfaces, which can potentiate clot formation. Thus, we revealed procoagulant activity of MSCs/EVs associated with the presence of phosphatidylserine and tissue factor, which requires further analysis to avoid adverse effects of MSC therapy in patients with a risk of thrombosis.
Microtubular and Nuclear Functions of γ-Tubulin: Are They LINCed?
Authors: Chumová Jana , Kourová Hana , Trögelová Lucie , Halada Petr , Binarová Pavla
Published: March 2019

γ-Tubulin is a conserved member of the tubulin superfamily with a function in microtubule nucleation. Proteins of γ-tubulin complexes serve as nucleation templates as well as a majority of other proteins contributing to centrosomal and non-centrosomal nucleation, conserved across eukaryotes. There is a growing amount of evidence of γ-tubulin functions besides microtubule nucleation in transcription, DNA damage response, chromatin remodeling, and on its interactions with tumor suppressors. However, the molecular mechanisms are not well understood. Furthermore, interactions with lamin and SUN proteins of the LINC complex suggest the role of γ-tubulin in the coupling of nuclear organization with cytoskeletons. γ-Tubulin that belongs to the clade of eukaryotic tubulins shows characteristics of both prokaryotic and eukaryotic tubulins. Both human and plant γ-tubulins preserve the ability of prokaryotic tubulins to assemble filaments and higher-order fibrillar networks. γ-Tubulin filaments, with bundling and aggregating capacity, are suggested to perform complex scaffolding and sequestration functions. In this review, we discuss a plethora of γ-tubulin molecular interactions and cellular functions, as well as recent advances in understanding the molecular mechanisms behind them.
Structure Based Design and Molecular Docking Studies for Phosphorylated Tau Inhibitors in Alzheimer’s Disease
Authors: Pradeepkiran Jangampalli Adi , Reddy P. Hemachandra
Published: March 2019

The purpose of our study is to identify phosphorylated tau (p-tau) inhibitors. P-tau has recently received great interest as a potential drug target in Alzheimer’s disease (AD). The continuous failure of Aβ-targeted therapeutics recommends an alternative drug target to treat AD. There is increasing evidence and growing awareness of tau, which plays a central role in AD pathophysiology, including tangles formation, abnormal activation of phosphatases/kinases, leading p-tau aggregation in AD neurons. In the present study, we performed computational pharmacophore models, molecular docking, and simulation studies for p-tau in order to identify hyperphosphorylated sites. We found multiple serine sites that altered the R1/R2 repeats flanking sequences in the tau protein, affecting the microtubule binding ability of tau. The ligand molecules exhibited the p-O ester scaffolds with inhibitory and/or blocking actions against serine residues of p-tau. Our molecular docking results revealed five ligands that showed high docking scores and optimal protein-ligand interactions of p-tau. These five ligands showed the best pharmacokinetic and physicochemical properties, including good absorption, distribution, metabolism, and excretion (ADME) and admetSAR toxicity tests. The p-tau pharmacophore based drug discovery models provide the comprehensive and rapid drug interventions in AD, and tauopathies are expected to be the prospective future therapeutic approach in AD.
A Direct Effect of Sex Hormones on Epithelial Barrier Function in Inflammatory Bowel Disease Models
Authors: van der Giessen Janine , van der Woude C. Janneke , Peppelenbosch Maikel P. , Fuhler Gwenny M.
Published: March 2019

Background: Pregnancy is often described as an immune-tolerant state, and a disease modulatory role for pregnancy on inflammatory bowel disease (IBD) has been suggested. The direct effect of estrogen and progesterone on the intestinal epithelial barrier is underexplored. We investigated the direct consequences of these pregnancy hormones on barrier cells and their function. Methods: We used IBD patient-derived inflammatory organoid models and 2D cell lines models. Epithelial barrier function was analyzed by measuring transepithelial electrical resistance; wound closure was determined by scratch assay; and cell viability was measured by MTT assays. Pro-inflammatory cytokine production was determined by enzyme-linked immunosorbent assays. Molecular modulation of endoplasmic reticulum (ER) stress induced by tunicamycin was studied by western blot analysis of the ER stress markers GRP78, CHOP and p-IRE1. Results: Progesterone and estrogen improved wound healing and epithelial barrier function in intestinal epithelial cells via upregulation of tight junction proteins. Furthermore, these sex hormones significantly reduced ER-stress and reduce pro-inflammatory cytokine production in intestinal epithelial models. Conclusion: Our study shows that estrogen and progesterone alleviate ER stress, decrease pro-inflammatory cytokine production, stimulate wound healing, and increase barrier function of epithelial cells. Combined, these data suggest that pregnancy hormones can have beneficial effects on disease activity by positively modulating the intestinal epithelial lining.
The North Atlantic Oscillations: Cycle Times for the NAO, the AMO and the AMOC
Authors: Seip Knut Lehre , Grøn Øyvind , Wang Hui
Published: March 2019

We show that oceanic cycle lengths persist across oceanic cyclic time-series by comparing cycles in series that come from “sister” measurements in the North Atlantic Ocean. These are the North Atlantic oscillation (NAO), the Atlantic multidecadal oscillation (AMO) and the Atlantic meridional overturning circulation (AMOC). The raw NAO series, which is an extremely noisy series in its raw format, showed cycles at 7, 13, 20, 26 and 34 years that were common with, or overlapped, the other two series, and across increasing degrees of smoothing of the NAO series. At the 1960 midpoint of the hiatus period 1943–1975, NAO was leading time-series to AMOC and AMO and AMO was a leading time-series to AMOC, but in 1975, at the end of the hiatus period, the leading relations were reversed.