bluuebunny/crossref_metadata_2025 huggingface dataset:
PERANCANGAN SISTEM INFORMASI SMART CLUSTER BANDUNG
Authors: Prasetyo Titis
Published: October 2019

The purpose of this study is to provide assistance to citizens in terms of correspondence between citizens and heads of citizens and discussion forums for citizens to interact with each other. Smart Cluster Bandung is an application that was created and developed by Universitas Komputer Indonesia students. Smart Cluster Bandung is a CSR (Corporate Social Responsibility) program as a form of the company's duties and responsibilities towards its social environment. In this case, the Bandung smart cluster makes the media to bridge between citizens and head of citizens. As well as a means of strengthening relations between citizens. Using this facility can be used as a place to stay in touch with local residents. In this study using a development system prototype. While the research method used is descriptive discussion by conducting interviews and observations. The results of this study provide positive results for residents in the cluster.
ANALISIS KUALITAS LAYANAN INTERNET DI PULAU BELAKANG PADANG DENGAN METODE QOS
Authors: Siyamto Yuli
Published: October 2019

Penelitian ini dilatarbelakangi tren peningkatan jumlah masyarakat pesisir Kota Batam yang memanfaatkan internet khususnya pulau Belakang Padang. Melalui internet, masyarakat dapat membuka wawasan, ilmu pengetahuan, ketrampilan, pangsa pasar serta peluang usaha yang lebih luas. Kelebihan smartphone adalah tidak tergantung sepenuhnya pada kondisi listrik PLN, memiliki fleksibelitas yang tinggi, dan sebagainya. Hal ini sangat tepat mengingat kondisi infrastruktur pelayanan listrik di daerah pesisir yang masih terbatas. Metode penelitian yang digunakan adalah metode QoS (Quality Of Service), dengan parameter utama throughput, delay, packet loss, dan jitter. Sedangkan standar yang digunakan referensi adalah TIPHON (Telecommunications and Internet Protocol Harmonization over Networks). Hasil dari penelitian akan diperoleh gambaran kualitas layanan jaringan internet berbasis seluler di daerah Belakang Padang dari berbagai penyedia layanan ISP (Internet Service Provider). Tujuan akhir penelitian ini adalah menjadi masukan bagi Pemerintah Kota Batam dan pihak swasta dalam rangka bersama-sama membangun Kota Batam lebih adil dan merata
Piperlongumine, a Novel TrxR1 Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cells by ROS-Mediated ER Stress
Authors: Zhang Qianqian , Chen Weiqian , Lv Xiuling , Weng Qiaoyou , Chen Minjiang , Cui Ri , Liang Guang , Ji Jiansong
Published: October 2019

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related deaths globally. Despite advances in diagnosis and treatment, the incidence and mortality of HCC continue to rise. Piperlongumine (PL), an alkaloid isolated from the fruit of the long pepper, is known to selectively kill tumor tissues while sparing their normal counterparts. However, the killing effects of PL on HCC and the underlying mechanism of PL are not clear. We report that PL may interact with thioredoxin reductase 1 (TrxR1), an important selenocysteine (Sec)-containing antioxidant enzyme, and induce reactive oxygen species (ROS)-mediated apoptosis in HCC cells. Our results suggest that PL induces a lethal endoplasmic reticulum (ER) stress response in HCC cells by targeting TrxR1 and increasing intracellular ROS levels. Notably, PL treatment reduces TrxR1 activity and tumor cell burden in vivo. Additionally, TrxR1 is significantly upregulated in existing HCC databases and available HCC clinical specimens. Taken together, these results suggest PL as a novel anticancer candidate for the treatment of HCC. More importantly, this study reveals that TrxR1 might be an effective target in treating HCC.
Effects of the Feed: Water Mixing Proportion on Diet Digestibility of Growing Pigs
Authors: Sol Cinta , Castillejos Lorena , López-Vergé Sergi , Muns Ramon , Gasa Josep
Published: October 2019

The effect of different water-to-feed ratios on apparent total tract digestibility of energy and nutrients were evaluated in growing–finishing pigs. In trial 1 (26 d), 16 female pigs (46.7 ± 1.98 kg of body weight, BW) were individually assigned to four treatments (n = 4). In trial 1, pigs were fed a control diet in dry form (CON) and in blend form with water-to-feed ratios of 0.6:1, 2.1:1 and 2.7:1. In trial 2 (26 d), rearranged animals (65.4 ± 3.14 kg of BW) were assigned a control diet in dry form (CON) and ratios of 1.35:1, 2.7:1 and 3.5:1. In trial 1, pigs fed on ratios of 2.1:1 and 2.7:1 had a higher organic matter digestibility (OMd) and gross energy digestibility (GEd) than CON. In trial 2, pigs fed on ratios of 1.35:1, 2.7:1, and 3.5:1 had a higher OMd and GEd than CON. Quadratic regressions showed the maximum dilution rate to reach higher digestibility coefficients at 1.83:1 and at 2.7:1 for trials 1 and 2, respectively. During trial 1, pigs on the 0.6:1 dilution rate had higher weight gain than those on CON. The water-to-feed ratio that optimized OM and GE digestibility may increase with the age of the pigs.
The Role of Oxytocin in the Dog–Owner Relationship
Authors: Marshall-Pescini Sarah , Schaebs Franka S. , Gaugg Alina , Meinert Anne , Deschner Tobias , Range Friederike
Published: October 2019

Oxytocin (OT) is involved in multiple social bonds, from attachment between parents and offspring to “friendships”. Dogs are an interesting species in which to investigate the link between the oxytocinergic system and social bonds since they establish preferential bonds with their own species but also with humans. Studies have shown that the oxytocinergic system may be involved in the regulation of such inter-specific relationships, with both dogs and their owners showing an increase in OT levels following socio-positive interactions. However, no direct comparison has been made in dogs’ OT reactivity following a social interaction with the owner vs. a familiar (but not bonded) person, so it is unclear whether relationship type mediates OT release during socio-positive interactions or whether the interaction per se is sufficient. Here we investigated OT reactivity in both dogs and owners, following a socio-positive interaction with each other or a familiar partner. Results showed neither the familiarity with the partner, nor the type of interaction affected OT reactivity (as measured in urine) in either dogs or owners. Given the recent mixed results on the role of oxytocin in dog-human interactions, we suggest there is a need for greater standardization of methodologies, an assessment of overall results taking into account ‘publication bias’ issues, and further studies investigating the role of relationship quality and interaction type on OT release.
The Sleep of Shelter Dogs Was Not Disrupted by Overnight Light Rather than Darkness in a Crossover Trial
Authors: Houpt Katherine , Erb Hollis , Coria-Avila Genaro
Published: October 2019

Dogs in shelters may be unattended at night. The purpose of this study is to describe the night-time behavior of dogs in a shelter and to determine if artificial light affected their sleeping patterns. Ten dogs were video-recorded under both light and dark conditions and their behavior recorded using focal animal sampling. The dogs were lying down 649 ± 40 min (mean ± SD) in the light condition and 629 ± 58 min in the dark condition each night. They awoke, stood up, turned around and then lay down again every 48 to 50 min. There was no significant difference in time spent lying between the two conditions (p > 0.05). Light did not seem to affect their behavior. The conclusion is that dogs in shelters may sleep in the absence of people and that light does not disrupt their sleep patterns.
Body Condition Score and Milk Production on Conception Rate of Cows under a Small-Scale Dairy System
Authors: Montiel-Olguín Luis Javier , Ruiz-López Felipe J. , Mellado Miguel , Estrada-Cortés Eliab , Gómez-Rosales Sergio , Elton-Puente Juana Elizabeth , Vera-Avila Hector Raymundo
Published: October 2019

Management and production characteristics impact conception rate to first service (CR1S) in small-scale dairy farms, but the impact of body condition score (BCS) and milk production levels on cows’ fertility is unknown. Our objective is to determine the effect of BCS and milk production on CR1S in small-scale dairy farms of western Mexico. Logistic regression models are used to determine the effect of BCS (at calving and first service), 60-d and 305-d milk production, protein and fat production, lactation number, and days at first service on CR1S. BCS at calving does not affect CR1S in cows with three or more lactations (39.5%; p > 0.1). However, first-lactation cows with BCS < 3.0 at calving and second lactation cows with BCS ≤ 2.5 at calving have higher CR1S (63.2 and 67.9%, respectively; p < 0.1). This result is perhaps due to reduced milk production, which leads to lower metabolic stress. BCS ≤ 2.5 at calving is associated (p < 0.05) with a reduced milk yield, explaining partially the observed higher CR1S in these groups. Cows with BCS ≤ 2.5 at first service in the higher quartile of 60-d milk production (≥ 28kg/day) show lower CR1S (23.9 and 51.1%, respectively; p < 0.01). In conclusion, BCS at calving and at first service, 60-d milk production, and lactation number are factors associated with CR1S.
Weber’s Law and the Scalar Property of Timing: A Test of Canine Timing
Authors: Cliff Jessica , Jackson Surrey , McEwan James , Bizo Lewis
Published: October 2019

Domestic dogs completed a temporal bisection procedure that required a response to one lever following a light stimulus of short duration and to another lever following a light stimulus of a longer duration. The short and long durations across the four conditions were (0.5–2.0 s, 1.0–4.0 s, 2.0–8.0 s, and 4.0–16.0 s). Durations that were intermediate, the training durations, and the training durations, were presented during generalization tests. The dogs bisected the intervals near the geometric mean of the short and long-stimulus pair. Weber fractions were not constant when plotted as a function of time: A U-shaped function described them. These results replicate the findings of previous research reporting points of subjective equality falling close to the geometric mean and also confirm recent reports of systematic departures from Weber’s law.
Understanding the Fracture Behaviors of Metallic Glasses—An Overview
Authors: Yang Guan-Nan , Shao Yang , Yao Ke-Fu
Published: October 2019

Fracture properties are crucial for the applications of structural materials. The fracture behaviors of crystalline alloys have been systematically investigated and well understood. The fracture behaviors of metallic glasses (MGs) are quite different from that of conventional crystalline alloys and have drawn wide interests. Although a few reviews on the fracture and mechanical properties of metallic glasses have been published, an overview on how and why metallic glasses fall out of the scope of the conventional fracture mechanics is still needed. This article attempts to clarify the up-to-date understanding of the question. We review the fracture behaviors of metallic glasses with the related scientific issues including the mode I fracture, brittle fracture, super ductile fracture, impact toughness, and fatigue fracture behaviors. The complex fracture mechanism of MGs is further discussed from the perspectives of discontinuous stress/strain field, plastic zone, and fracture resistance, which deviate from the classic fracture mechanics in polycrystalline alloys. Due to the special deformation mechanism, metallic glasses show a high variability in fracture toughness and other mechanical properties. The outlook presented by this review could help the further studies of metallic glasses. The review also identifies some key questions to be answered.
Joint User Pairing, Channel Assignment and Power Allocation in NOMA based CR Systems
Authors: Ali Zain , Rao Yanyi , Khan Wali Ullah , Sidhu Guftaar Ahmad Sardar
Published: October 2019

The fifth generation (5G) wireless communication systems promise to provide massive connectivity over the limited available spectrum. Various new transmission paradigms such as non-orthogonal multiple access (NOMA) and cognitive radio (CR) have emerged as potential 5G enabling technologies. These techniques offer high spectral efficiency by allowing multiple users to communicate on the same frequency channel, simultaneously. A combination of both techniques may further enhance the performance of the system. This work aims to maximize the achievable rate of a multi-user multi-channel NOMA based CR system. We propose an efficient user pairing, channel assignment and power optimization technique for the secondary users while the performance of primary users is guaranteed through interference temperature limits. The results show that, at small values of the power budget or high interference threshold, optimizing channel allocation and user pairing proves to be more beneficial than optimal power allocation to the user pairs. The proposed joint optimization technique provides promising results for all values of the power budget, interference threshold and rate requirement of the communicating users.
Hybrid Edge–Cloud-Based Smart System for Chatter Suppression in Train Wheel Repair
Authors: Merino Ruben , Bediaga Iñigo , Iglesias Alexander , Munoa Jokin
Published: October 2019

The contact profile of a train wheel has a key role in its operation performance. Rolling smoothly and with reduced resistance results in an increase in the efficiency and safety of rail transport. The original shape and dimensions of the profile of the wheel are altered under operation of the train, especially due to braking events and the presence of external objects between the wheel and the railway. With the purpose of recovering the optimum contact profile, train wheels are periodically machined using special lathes. This repair operation is particularly critical in freight trains, which are only reshaped a few times throughout their service life and, therefore, high depths of cut are required to recover the wheel in a productive way. As the presence of chatter vibrations limits the productivity of these operations, a hybrid edge–cloud computing approach has been developed for chatter vibration suppression. An expert system based on automatic chatter detection and suppression has been developed in the edge. The expert system is based on continuous real-time vibration monitoring and combines continuous spindle speed variation (CSSV) and cutting speed reduction to suppress chatter. Cloud computing is used to extract wheel profile machining fingerprints and obtain insights from multiple aggregated machined wheels. An industrial implementation of the system is described in the present work.
Parameter Estimation with the Ordered ℓ2 Regularization via an Alternating Direction Method of Multipliers
Authors: Humayoo Mahammad , Cheng Xueqi
Published: October 2019

Regularization is a popular technique in machine learning for model estimation and for avoiding overfitting. Prior studies have found that modern ordered regularization can be more effective in handling highly correlated, high-dimensional data than traditional regularization. The reason stems from the fact that the ordered regularization can reject irrelevant variables and yield an accurate estimation of the parameters. How to scale up the ordered regularization problems when facing large-scale training data remains an unanswered question. This paper explores the problem of parameter estimation with the ordered ℓ 2 -regularization via Alternating Direction Method of Multipliers (ADMM), called ADMM-O ℓ 2 . The advantages of ADMM-O ℓ 2 include (i) scaling up the ordered ℓ 2 to a large-scale dataset, (ii) predicting parameters correctly by excluding irrelevant variables automatically, and (iii) having a fast convergence rate. Experimental results on both synthetic data and real data indicate that ADMM-O ℓ 2 can perform better than or comparable to several state-of-the-art baselines.
Special Issue on HVDC for Grid Services in Electric Power Systems
Authors: Jang Gilsoo
Published: October 2019

The modern electric power system has evolved into a huge nonlinear complex system, due to the interconnection of a lot of generation and transmission systems [...]
Two-Step Feature Selection for Identifying Developmental Differences in Resting fMRI Intrinsic Connectivity Networks
Authors: Qiao Chen , Gao Bin , Lu Lu-Jia , Calhoun Vince D. , Wang Yu-Ping
Published: October 2019

Functional connectivity derived from functional magnetic resonance imaging (fMRI) is used as an effective way to assess brain architecture. There has been a growing interest in its application to the study of intrinsic connectivity networks (ICNs) during different brain development stages. fMRI data are of high dimension but small sample size, and it is crucial to perform dimension reduction before pattern analysis of ICNs. Feature selection is thus used to reduce redundancy, lower the complexity of learning, and enhance the interpretability. To study the varying patterns of ICNs in different brain development stages, we propose a two-step feature selection method. First, an improved support vector machine based recursive feature elimination method is utilized to study the differences of connectivity during development. To further reduce the highly correlated features, a combination of F-score and correlation score is applied. This method was then applied to analysis of the Philadelphia Neurodevelopmental Cohort (PNC) data. The two-step feature selection was randomly performed 20 times, and those features that showed up consistently in the experiments were chosen as the essential ICN differences between different brain ages. Our results indicate that ICN differences exist in brain development, and they are related to task control, cognition, information processing, attention, and other brain functions. In particular, compared with children, young adults exhibit increasing functional connectivity in the sensory/somatomotor network, cingulo-opercular task control network, visual network, and some other subnetworks. In addition, the connectivity in young adults decreases between the default mode network and other subnetworks such as the fronto-parietal task control network. The results are coincident with the fact that the connectivity within the brain alters from segregation to integration as an individual grows.
The Effect of Patellar Tendon Release on the Characteristics of Patellofemoral Joint Squat Movement: A Simulation Analysis
Authors: Wang Jianping , Yang Yongqiang , Guo Dong , Wang Shihua , Fu Long , Li Yu
Published: October 2019

Objectives: This paper studies the patellar tendon release’s effect on the movement characteristics of the artificial patellofemoral joint squat to provide reference data for knee joint surgery. Methods: Firstly, the dynamic finite element model of the human knee joint under squatting was established. Secondly, in the above no-release models, the release of 30% of the attachment area at the upper end, the lower end, or both ends of the patellar tendon were conducted, respectively. Then the simulations of all above four models were conducted. Finally, the results of the simulation were compared and analyzed. Results: The simulation results show that, after releasing the patellar tendon (compared with the no-release simulation’s results), the relative flexion, medial-lateral rotation, medial-lateral tilt, and superior-inferior shift of the patella relative to the femur increased; the medial-lateral shift and anterior-posterior shift of the patella relative to the femur decreased. Conclusion: In this paper, the maximum flexion angle of the patella increased after the patellar tendon being released (compared with the no-release model), which indicated that the mobility of knee joint was improved after the patellar tendon release. The simulation data in this paper can provide technical reference for total knee arthroplasty.
Cooking/Window Opening and Associated Increases of Indoor PM2.5 and NO2 Concentrations of Children’s Houses in Kaohsiung, Taiwan
Authors: Yen Yu-Chuan , Yang Chun-Yuh , Mena Kristina , Cheng Yu-Ting , Chen Pei-Shih
Published: October 2019

High concentrations of air pollutants and increased morbidity and mortality rates are found in industrial areas, especially for the susceptible group, children; however, most studies use atmospheric dispersion modeling to estimate household air pollutants. Therefore, the aim of this study was to assess the indoor air quality, e.g., CO, CO2, NO2, SO2, O3, particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5), and their influence factors in children’s homes in an industrial city. Children in the “general school”, “traffic school”, and “industrial school” were randomly and proportionally selected. Air pollutants were sampled for 24 h in the living rooms and on the balcony of their houses and questionnaires of time–microenvironment–activity-diary were recorded. The indoor CO concentration of the traffic area was significantly higher than that of the industrial area and the general area. In regard to the effects of window opening, household NO2 and PM2.5 concentrations during window opening periods were significantly higher than of the reference periods. For the influence of cooking, indoor CO2, NO2, and PM2.5 levels during the cooking periods were significantly higher than that of the reference periods. The indoor air quality of children in industrial cities were affected by residential areas and household activities.
Model Updating Using Measurements from Sensors Installed in Arbitrary Positions and Directions
Authors: Cho Keunhee , Park Young-Hwan , Cho Jeong-Rae
Published: October 2019

The present study proposes a method for model updating using measurements from sensors installed in arbitrary positions and directions. Modal identification provides mode shapes for physical quantities (acceleration strain, etc.) measured in specific directions at the location of the sensors. Besides, model updating involves the use of the mode shapes related to the nodal degrees-of-freedom of the finite element analytic model. Consequently, the mode shapes obtained by modal identification and the mode shapes of the model updating process do not coincide even for the same mode. Therefore, a method for constructing transform matrices that distinguish the cases where measurement is done by acceleration, velocity, and displacement sensors and the case where measurement is done by strain sensors was proposed to remedy such disagreement among the mode shapes. The so-constructed transform matrices were then applied when the mode shape residual was used as the objective function or for mode pairing in the model updating process. The feasibility of the proposed approach was verified by means of a numerical example in which the strain or acceleration of a simple beam was measured and a numerical example in which the strain of a bridge was measured. Using the proposed approach, it was possible to model the structure regardless of the position of the sensors and to select the location of the sensors independently from the model.
Coordinated Formation Design of Multi-Robot Systems via an Adaptive-Gain Super-Twisting Sliding Mode Method
Authors: Qian Dianwei , Zhang Guigang , Chen Jiarong , Wang Jian , Wu Zhimin
Published: October 2019

This paper presents a super-twisting-based sliding mode control method for the formation problem of multi-robot systems. The multiple robots contain plenty of uncertainties and disturbances. Such a control method has two adaptive gains that can contribute to the robustness and improve the response of the formation maneuvers despite these uncertainties and disturbances. Based on the leader-follower frame, this control method was investigated. The closed-loop formation stability is theoretically guaranteed in the sense of Lyapunov. From the aspect of practice, the control method was carried out by a multi-robot system to achieve some desired formation patterns. Some numerical results were demonstrated to verify the feasibility of the control method. Some comparisons were also illustrated to support the superiority and effectiveness of the presented sliding mode control method.
An Integrated Approach Supporting Remediation of an Aquifer Contaminated with Chlorinated Solvents by a Combination of Adsorption and Biodegradation
Authors: Ciampi Paolo , Esposito Carlo , Viotti Paolo , Boaga Jacopo , Cassiani Giorgio , Petrangeli Papini Marco
Published: October 2019

Hydrogeological uniqueness and chemical-physical peculiarities guide the contamination dynamics and decontamination mechanisms in the environmental arena. A single composite geodatabase, which integrates geological/hydrological, geophysical, and chemical data, acts as a “cockpit” in the definition of a conceptual model, design of a remediation strategy, implementation, near-real-time monitoring, and validation/revision of a pilot test, and monitoring full-scale interventions. The selected remediation strategy involves the creation of "reactive" zones capable of reducing the concentration of chlorinated solvents in groundwater through the combined action of adsorption on micrometric activated carbon, which is injected into the aquifer, and degradation of organic contaminants, stimulating the dechlorinating biological activity by the addition of an electron donor. The technology is verified through a pilot test, to evaluate the possibility of scaling up the process. The results of post-treatment monitoring reveal abatement of the concentration of chlorinated solvents and intense biological dechlorination activity. Achieving the remediation objectives and project closure is based on the integration of multidisciplinary data using a multiscale approach. This research represents the first completed example in European territory of remediation of an aquifer contaminated with chlorinated solvents by a combination of adsorption and biodegradation.
Recovery and Elimination of Phenolic Pollutants from Water Using [NTf2] and [Nf2]-Based Ionic Liquids
Authors: Sas Olalla G. , Domínguez Ángeles , González Begoña
Published: October 2019

At present, pollution is one of the most important problems worldwide. Industrial growth makes it necessary to develop techniques to remove pollutant substances from water, since water is an important natural source for life. One of these techniques is liquid–liquid extraction, which is used to remove phenolic compounds from wastewaters. Volatile organic compounds are used as common extraction solvents in liquid–liquid extractions; nevertheless, some of their properties, such as toxicity and volatility, make it necessary to replace them with other less toxic solvents. In this work, the capability of four ionic liquids, based on bis(trifluoromethylsulfonyl)imide [NTf2] and bis(fluorosulfonyl)imide [Nf2] anions and different cations to remove phenolic compounds from water was studied. The phenolic compounds used in this study were phenol, o-cresol, and 2-chlorophenol, and the effects of the extraction solvent and phenol structures were analyzed. For that, a liquid–liquid extraction was carried out, and the extraction yield was determined. In general, high extraction efficiencies were obtained for all studied systems, obtaining the highest extraction efficiencies using the pyrrolidinium cation-based ionic liquids.
Oxidation Stress-Mediated MAPK Signaling Pathway Activation Induces Neuronal Loss in the CA1 and CA3 Regions of the Hippocampus of Mice Following Chronic Cold Exposure
Authors: Xu Bin , Lang Li-Min , Lian Shuai , Guo Jing-Ru , Wang Jian-Fa , Yang Huan-Min , Li Shi-Ze
Published: October 2019

Chronic stress can damage homeostasis and induce various primary diseases. Although chronic cold stress is becoming an increasing problem for people who must work or live in extreme environments, risk-induced diseases in the central nervous system remain unstudied. Male C57BL/6 mice were exposed to an environment of 4 °C, 3 h per day for 1, 2, and 3 weeks and homeostasis in the hippocampus and neuronal apoptosis were evaluated by Western blotting, immunohistochemistry, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunofluorescence. The phenomena of oxidation stress, MAPK signaling pathway activation, anti-oxidation protein release, neuronal apoptosis increases, and neuronal proliferation inhibition were demonstrated in the CA1 and CA3 regions of mouse hippocampal tissues following cold exposure. We speculated that these phenomena were mediated by the MAPK pathway and were closely linked with oxidative stress in the hippocampus. This study provides novel concepts regarding neurodegenerative diseases, suggesting that chronic cold stress may be a critical factor to induce neurodegenerative diseases.
Simultaneous Inhibition of BCR-ABL1 Tyrosine Kinase and PAK1/2 Serine/Threonine Kinase Exerts Synergistic Effect against Chronic Myeloid Leukemia Cells
Authors: Flis Sylwia , Bratek Ewelina , Chojnacki Tomasz , Piskorek Marlena , Skorski Tomasz
Published: October 2019

Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia in the chronic phase (CML-CP). However, it is unlikely that they can completely “cure” the disease. This might be because some subpopulations of CML-CP cells such as stem and progenitor cells are resistant to chemotherapy, even to the new generation of TKIs. Therefore, it is important to look for new methods of treatment to improve therapeutic outcomes. Previously, we have shown that class I p21-activated serine/threonine kinases (PAKs) remained active in TKI-naive and TKI-treated CML-CP leukemia stem and early progenitor cells. In this study, we aimed to determine if simultaneous inhibition of BCR-ABL1 oncogenic tyrosine kinase and PAK1/2 serine/threonine kinase exert better anti-CML effect than that of individual treatments. PAK1 was inhibited by small-molecule inhibitor IPA-3 (p21-activated kinase inhibitor III), PAK2 was downregulated by specific short hairpin RNA (shRNA), and BCR-ABL1 tyrosine kinase was inhibited by imatinib (IM). The studies were conducted by using (i) primary CML-CP stem/early progenitor cells and normal hematopoietic counterparts isolated from the bone marrow of newly diagnosed patients with CML-CP and from healthy donors, respectively, (ii) CML-blast phase cell lines (K562 and KCL-22), and (iii) from BCR-ABL1-transformed 32Dcl3 cell line. Herein, we show that inhibition of the activity of PAK1 and/or PAK2 enhanced the effect of IM against CML cells without affecting the normal cells. We observed that the combined use of IM with IPA-3 increased the inhibition of growth and apoptosis of leukemia cells. To evaluate the type of interaction between the two drugs, we performed median effect analysis. According to our results, the type and strength of drug interaction depend on the concentration of the drugs tested. Generally, combination of IM with IPA-3 at the 50% of the cell kill level (EC50) generated synergistic effect. Based on our results, we hypothesize that IM, a BCR-ABL1 tyrosine kinase inhibitor, combined with a PAK1/2 inhibitor facilitates eradication of CML-CP cells.
Inherited Variants in BLM and the Risk and Clinical Characteristics of Breast Cancer
Authors: Kluźniak Wojciech , Wokołorczyk Dominika , Rusak Bogna , Huzarski Tomasz , Kashyap Aniruddh , Stempa Klaudia , Rudnicka Helena , Jakubowska Anna , Szwiec Marek , Morawska Sylwia , Gliniewicz Katarzyna , Mordak Karina , Stawicka Małgorzata , Jarkiewicz-Tretyn Joanna , Cechowska Magdalena , Domagała Paweł , Dębniak Tadeusz , Lener Marcin , Gronwald Jacek , Lubiński Jan , Narod Steven A. , Akbari Mohammad R. , Cybulski Cezary
Published: October 2019

Bloom Syndrome is a rare recessive disease which includes a susceptibility to various cancers. It is caused by homozygous mutations of the BLM gene. To investigate whether heterozygous carriers of a BLM mutation are predisposed to breast cancer, we sequenced BLM in 617 patients from Polish families with a strong family history of breast cancer. We detected a founder mutation (c.1642C>T, p.Gln548Ter) in 3 of the 617 breast cancer patients (0.49%) who were sequenced. Then, we genotyped 14,804 unselected breast cancer cases and 4698 cancer-free women for the founder mutation. It was identified in 82 of 14,804 (0.55%) unselected cases and in 26 of 4698 (0.55%) controls (OR = 1.0; 95%CI 0.6–1.6). Clinical characteristics of breast cancers in the BLM mutation carriers and non-carriers were similar. Loss of the wild-type BLM allele was not detected in cancers from the BLM mutation carriers. No cancer type was more common in the relatives of mutation carriers compared to relatives of non-carriers. The BLM founder mutation p.Gln548Ter, which in a homozygous state is a cause of Bloom syndrome, does not appear to predispose to breast cancer in a heterozygous state. The finding casts doubt on the designation of BLM as an autosomal dominant breast cancer susceptibility gene.
Oxidized Palladium Supported on Ceria Nanorods for Catalytic Aerobic Oxidation of Benzyl Alcohol to Benzaldehyde in Protic Solvents
Authors: Moeini Seyed , Battocchio Chiara , Casciardi Stefano , Luisetto Igor , Lupattelli Paolo , Tofani Daniela , Tuti Simonetta
Published: October 2019

In the present study, the catalytic activity of palladium oxide (PdOx) supported on ceria nanorods (CeO2-NR) for aerobic selective oxidation of benzyl alcohol (BnOH) to benzaldehyde (PhCHO) was evaluated. The CeO2-NR was synthesized hydrothermally and the Pd(NO3)2 was deposited by a wet impregnation method, followed by calcination to acquire PdOx/CeO2-NR. The catalysts were characterized by X-ray diffraction (XRD), temperature programmed reduction (TPR), transmission electron microscopy (TEM), Brunauer–Emmet–Teller (BET) surface area analysis, and X-ray photoelectron spectroscopy (XPS). In addition, the TPR-reduced PdOx/CeO2-NR (PdOx/CeO2-NR-Red) was studied by XRD, BET, and XPS. Characterizations showed the formation of CeO2-NR with (111) exposed plane and relatively high BET surface area. PdOx (x > 1) was detected to be the major oxide species on the PdOx/CeO2-NR. The activities of the catalysts in BnOH oxidation were evaluated using air, as an environmentally friendly oxidant, and various solvents. Effects of temperature, solvent nature and palladium oxidation state were investigated. The PdOx/CeO2-NR showed remarkable activity when protic solvents were utilized. The best result was achieved using PdOx/CeO2-NR and boiling ethanol as solvent, leading to 93% BnOH conversion and 96% selectivity toward PhCHO. A mechanistic hypothesis for BnOH oxidation with PdOx/CeO2-NR in ethanol is presented.
Indium Tin-Oxide Wrapped 3D rGO and TiO2 Composites: Development, Characterization, and Enhancing Photocatalytic Activity for Methylene Blue
Authors: Gong Cheng , Xu Shiyin , Xiao Peng , Liu Feifan , Xu Yunhui , Yang Jin , Li Rui , Wang Xuan , Du Jun , Peng Hailong
Published: October 2019

A hybrid material of indium tin-oxide (ITO) wrapped titanium dioxide and reduced graphene oxide (ITO-rGO and TiO2) was prepared using a facile hydrothermal technique. TiO2 nanorods were in situ grown on the surface of rGO (rGO and TiO2), and which was then assembled onto ITO substrate layer by layer with formation of a 3D structure. ITO-rGO and TiO2 exhibit low charge transfer resistance at the electrode-electrolyte interface and have good photoresponsive ability. Methylene blue (MB) can be effectively adsorbed and enriched onto ITO-rGO and TiO2 surface. The adsorption kinetics and thermodynamics of ITO-rGO and TiO2 were evaluated, showing that the exothermic and entropy-driven reaction were the main thermodynamic processes, and the Langmuir isotherm was the ideal model for adsorption fitting. Meanwhile, ITO greatly improved degradation of rGO and TiO2 because electrons can be collected by ITO before recombination and MB can easily enter into the 3D structure of rGO and TiO2. The highest photodegradation rate of MB reached 93.40% for ITO-rGO and TiO2 at pH 9. Additionally, ITO-rGO and TiO2 successfully solved the problems of being difficult to recycle and causing secondary pollution of traditional TiO2 catalysts. Therefore, ITO-rGO and TiO2 may be a potential photocatalyst for degrading organic pollutants in water.
Nanomaterials for Environmental Purification and Energy Conversion
Authors: Kowalska Ewa , Markowska-Szczupak Agata , Janczarek Marcin
Published: October 2019

Nanomaterials, engineered structures of which a single unit is sized (in at least one dimension) between 1 to 100 nm, are probably the fastest growing market in the world [...]
Development of Nickel-BTC-MOF-Derived Nanocomposites with rGO Towards Electrocatalytic Oxidation of Methanol and Its Product Analysis
Authors: Yaqoob Lubna , Noor Tayyaba , Iqbal Naseem , Nasir Habib , Zaman Neelam
Published: October 2019

In this study, electrochemical oxidation of methanol to formic acid using the economical and highly active catalytic Nickel Benzene tricarboxylic acid metal organic framework (Ni-BTC-MOF) and reduced graphene oxide (rGO) nanocomposites modified glassy carbon electrode GCE in alkaline media, which was examined via cyclic voltammetry technique. Nickel based MOF and rGO nanocomposites were prepared by solvothermal approach, followed by morphological and structural characterization of prepared samples through X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and energy dispersive X-ray (EDX) analysis. The electrochemical testing of synthesized materials represents the effect of the sequential increase in rGO concentration on electrocatalytic activity. The Ni-BTC/4 wt % rGO composite with a pronounced current density of 200.22 mA/cm2 at 0.69 V versus Hg/HgO electrode at 50 mV/s was found to be a potential candidate for methanol oxidation in Direct Methanol Fuel Cell (DMFC) applications. Product analysis was carried out through Gas Chromatography (GC) and Nuclear Magnetic Resonance (NMR) spectroscopy, which confirmed the formation of formic acid during the oxidation process, with approximately 62% yield.
The Role of Adenine Nucleotide Translocase in the Assembly of Respiratory Supercomplexes in Cardiac Cells
Authors: M. Parodi-Rullán Rebecca , Chapa-Dubocq Xavier , Guzmán-Hernández Roberto , Jang Sehwan , A. Torres-Ramos Carlos , Ayala-Peña Sylvette , Javadov Sabzali
Published: October 2019

Individual electron transport chain complexes have been shown to assemble into the supramolecular structures known as the respiratory chain supercomplexes (RCS). Several studies reported an associative link between RCS disintegration and human diseases, although the physiological role, structural integrity, and mechanisms of RCS formation remain unknown. Our previous studies suggested that the adenine nucleotide translocase (ANT), the most abundant protein of the inner mitochondrial membrane, can be involved in RCS assembly. In this study, we sought to elucidate whether ANT knockdown (KD) affects RCS formation in H9c2 cardiomyoblasts. Results showed that genetic silencing of ANT1, the main ANT isoform in cardiac cells, stimulated proliferation of H9c2 cardiomyoblasts with no effect on cell viability. ANT1 KD reduced the ΔΨm but increased total cellular ATP levels and stimulated the production of total, but not mitochondrial, reactive oxygen species. Importantly, downregulation of ANT1 had no significant effects on the enzymatic activity of individual ETC complexes I–IV; however, RCS disintegration was stimulated in ANT1 KD cells as evidenced by reduced levels of respirasome, the main RCS. The effects of ANT1 KD to induce RCS disassembly was not associated with acetylation of the exchanger. In conclusion, our study demonstrates that ANT is involved in RCS assembly.
Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements
Authors: Tuaeva Natalia O. , Falzone Luca , Porozov Yuri B. , Nosyrev Alexander E. , Trukhan Vladimir M. , Kovatsi Leda , Spandidos Demetrios A. , Drakoulis Nikolaos , Kalogeraki Alexandra , Mamoulakis Charalampos , Tzanakakis George , Libra Massimo , Tsatsakis Aristides
Published: October 2019

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients’ prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients’ samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.
An RBPJ-Drosophila Model Reveals Dependence of RBPJ Protein Stability on the Formation of Transcription–Regulator Complexes
Authors: Gahr Bernd M. , Brändle Franziska , Zimmermann Mirjam , Nagel Anja C.
Published: October 2019

Notch signaling activity governs widespread cellular differentiation in higher animals, including humans, and is involved in several congenital diseases and different forms of cancer. Notch signals are mediated by the transcriptional regulator RBPJ in a complex with activated Notch (NICD). Analysis of Notch pathway regulation in humans is hampered by a partial redundancy of the four Notch receptor copies, yet RBPJ is solitary, allowing its study in model systems. In Drosophila melanogaster, the RBPJ orthologue is encoded by Suppressor of Hairless [Su(H)]. Using genome engineering, we replaced Su(H) by murine RBPJ in order to study its function in the fly. In fact, RBPJ largely substitutes for Su(H)’s function, yet subtle phenotypes reflect increased Notch signaling activity. Accordingly, the binding of RBPJ to Hairless (H) protein, the general Notch antagonist in Drosophila, was considerably reduced compared to that of Su(H). An H-binding defective RBPJLLL mutant matched the respective Su(H)LLL allele: homozygotes were lethal due to extensive Notch hyperactivity. Moreover, RBPJLLL protein accumulated at lower levels than wild type RBPJ, except in the presence of NICD. Apparently, RBPJ protein stability depends on protein complex formation with either H or NICD, similar to Su(H), demonstrating that the murine homologue underlies the same regulatory mechanisms as Su(H) in Drosophila. These results underscore the importance of regulating the availability of RBPJ protein to correctly mediate Notch signaling activity in the fly.
Genome-Wide Mapping Defines a Role for C/EBPβ and c-Jun in Non-Canonical Cyclic AMP Signalling
Authors: Wiejak Jolanta , van Basten Boy , Hamilton Graham , Yarwood Stephen J.
Published: October 2019

The novel exchange protein activated by cyclic AMP (EPAC1) activator, I942, induces expression of the suppressor of cytokine signalling 3 (SOCS3) gene, thereby inhibiting interleukin 6 (IL6) inflammatory processes in human umbilical vein endothelial cells (HUVECs). Here we use RNA-SEQ and ChIP-SEQ to determine global gene responses to I942, in comparison with cyclic AMP production promoted by forskolin and rolipram (F/R). We found that I942 promoted significant changes in the RNA expression of 1413 genes, largely associated with microtubule stability and cell cycle progression, whereas F/R regulated 197 genes linked to endothelial cell function, including chemokine production and platelet aggregation. A further 108 genes were regulated by both treatments, including endothelial regulatory genes involved in purinergic signalling and cell junction organization. ChIP-SEQ demonstrated that F/R induced genome-wide recruitment of C/EBPβ and c-Jun transcription factors, whereas I942 promoted recruitment of c-Jun to genes associated with IL6 signalling, with little effect on C/EBPβ activation. Despite this, certain key inflammatory genes, including IL6, VEGF, CCL2/MCP1, VCAM1, SELE and ICAM1 were regulated by I942 without significant c-Jun recruitment, suggesting an additional, indirect mode of action for I942. In this regard, SOCS3 induction by I942 was found to require c-Jun and was associated with suppression of IL6-promoted ERK MAP kinase and AKT activity and induction of ICAM1. Pharmacological inhibition of ERK and AKT also potentiated ICAM1 induction by I942. We therefore propose that c-Jun activation by I942 regulates endothelial gene expression in HUVECs through direct mechanisms, involving recruitment of c-Jun or, as for ICAM1, through indirect regulation of tertiary regulators, including SOCS3.
A Facile Route to Fabricate Superhydrophobic Cu2O Surface for Efficient Oil–Water Separation
Authors: Lei Sheng , Fang Xinzuo , Wang Fajun , Xue Mingshan , Ou Junfei , Li Changquan , Li Wen
Published: October 2019

The mixture of insoluble organics and water seriously affects human health and environmental safety. Therefore, it is important to develop an efficient material to remove oil from water. In this work, we report a superhydrophobic Cu2O mesh that can effectively separate oil and water. The superhydrophobic Cu2O surface was fabricated by a facile chemical reaction between copper mesh and hydrogen peroxide solution without any low surface reagents treatment. With the advantages of simple operation, short reaction time, and low cost, the as-synthesized superhydrophobic Cu2O mesh has excellent oil–water selectivity for many insoluble organic solvents. In addition, it could be reused for oil–water separation with a high separation ability of above 95%, which demonstrated excellent durability and reusability. We expect that this fabrication technique will have great application prospects in the application of oil–water separation.
The Effect of Cathodic Arc Guiding Magnetic Field on the Growth of (Ti0.36Al0.64)N Coatings
Authors: Chaar Ana B. B. , Syed Bilal , Hsu Tun-Wei , Johansson-Jöesaar Mats , Andersson Jon M. , Henrion Gérard , Johnson Lars J. S. , Mücklich Frank , Odén Magnus
Published: October 2019

We use a modified cathodic arc deposition technique, including an electromagnetic coil that introduces a magnetic field in the vicinity of the source, to study its influence on the growth of (Ti0.36Al0.64)N coatings. By increasing the strength of the magnetic field produced by the coil, the cathode arc spots are steered toward the edge of the cathode, and the electrons are guided to an annular anode surrounding the cathode. As a result, the plasma density between the cathode and substrate decreased, which was observed as a lateral spread of the plasma plume, and a reduction of the deposition rate. Optical emission spectroscopy shows reduced intensities of all recorded plasma species when the magnetic field is increased due to a lower number of collisions resulting in excitation. We note a charge-to-mass ratio decrease of 12% when the magnetic field is increased, which is likely caused by a reduced degree of gas phase ionization, mainly through a decrease in N2 ionization. (Ti0.36Al0.64)N coatings grown at different plasma densities show considerable variations in grain size and phase composition. Two growth modes were identified, resulting in coatings with (i) a fine-grained glassy cubic and wurtzite phase mixture when deposited with a weak magnetic field, and (ii) a coarse-grained columnar cubic phase with a strong magnetic field. The latter conditions result in lower energy flux to the coating’s growth front, which suppresses surface diffusion and favors the formation of c-(Ti,Al)N solid solutions over phase segregated c-TiN and w-AlN.