bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGGUNAAN METODE SIMPLE ADDITIVE WEIGHTING (SAW) PADA SISTEM PENUNJANG KEPUTUSAN DALAM PENENTUAN JURUSAN SMK
Authors: Susliansyah Susliansyah
Published: January 2019

Sebagian besar siswa lulusan SMP berkeinginan untuk melanjutkan keinginannya khususnya ke SMK, hal tersebut dapat dibuktikan dengan banyaknya siswa lulusan SMP yang mengikuti ujian masuk ke SMK. Hal yang patut disayangkan adalah kurang matangnya mereka memilih jurusan yang ada di sekolah kejuruan yang dituju. Situasi semacam ini berdampak pada biaya pendidikan yang terlanjur di keluarkan, baik pada orang tua siswa maupun  pemerintah  yang  mensubsidi  sekolah  menjadi  tidak  bermanfaat  karna  siswa  tersebut  tidak  memiliki kemampuan yang memadai untuk jurusan yang sudah dipilihnya, akibat negatif lainya adalah para siswa yang drop out. SMK  lebih  mengedepankan  pembentukan  siswa  yang  siap  memasuki  lapangan  kerja  serta mengembangkan sikap profesional yang terdiri dari berbagai macam jurusan. Banyaknya jurusan pada tingkat SMK membuat calon siswa kesulitan menentukan jurusan yang tepat sesuai dengan kemampuan yang dimiliki, oleh karena itu  dibutuhkan  sebuah  sistem pendukung keputusan yang dapat menentukan jurusan sesuai dengan nilai, minat  dan  kemampuan  calon  siswa.  Penelitian  ini  menerapkan  logika  fuzzy  dengan  metode  Simple Additive Weighting (SAW) guna mempermudah penentuan jurusan SMK.
IMPLEMENTASI ALGORITMA APRIORI UNTUK ANALISA PEMILIHAN TIPE GENRE FILM ANIME (STUDI KASUS : MYANIMELIST.NET)
Authors: Azis Moch Abdul , Hadianto Nur , Miharja Jaja , Rifai Saifulloh
Published: January 2019

Seperti halnya film animasi jepang atau bisa juga di sebut dengan film anime yang kini mulai banyak digemari oleh semua kalangan tanpa pandang umur, status dan profesi. Pada film anime jepang ini memiliki memiliki beberapa genre dari action, comedy, drama, romance, adventure dll,  bisa diakses seperti pada media online seperti website yang menyajikan macam-macam genre anime salah satunya adalah myanimelist.net pada web ini memiliki 14.000 film anime berbagi genre. Salah satu cara untuk meningkatkan daya tarik film anime adalah dengan pemanfaatan data pelihan genre yang sering di tonton oleh para penikmat film anime. Dengan data tersebut kita busa menganalisa tipe genre apa yang paling banyak di tonton, serta kecenderungan pemilihan tipe genre alternatif yang disukai oleh para penikmat film anime. Sehingga dengan data-data tersebut pihak creator bisa menentukan strategi untuk realese tipe genre yang akan dibuat berikutnya. algoritma apriori bagus untuk digunakan untuk pembentukan itemset, pencarian pola dan lain sebagainya. Maka dari itu pada penelitian kali ini Algoritma apriori digunakan untuk menentukan pola pemililihan tipe genre pada Film Anime Jepang.
Continuidade e diferenciabilidade de funções reais: uma proposta de estudo dessas noções com a utilização do computador
Authors: Igliori Sonia Barbosa Camargo , Abar Celina Aparecida Almeida Pereira , De Almeida Marcio Vieira
Published: February 2019

Este artigo objetiva analisar a utilização dos computadores no ensino da noção de continuidade e diferenciabilidade de funções de uma variável real. A relação é abordada no caso de funções contínuas e não diferenciáveis em um intervalo real, por meio de um exemplo que foi encontrado em um artigo escrito por David Tall e utilizado para evidenciar uma forma pela qual o computador pode auxiliar no ensino e aprendizagem dos conceitos do Cálculo Diferencial e Integral quando materiais didáticos e significativos são produzidos. Elementos da teoria de Tall sobre as vantagens dos computadores na Educação, bem como a importância histórica do desenvolvimento de um exemplo de função contínua e não diferenciável são apresentados neste artigo. Além disso, é explorado o caso de uma função definida por um limite de uma série de funções. Também são apresentados comando e ferramentas que estão disponíveis no software GeoGebra. Como resultado, são apresentadas ferramentas que, possivelmente, podem contribuir com a prática, bem como avançar com a Educação Matemática no ensino superior.
Estudo das funções trigonométricas a partir da Teoria da Aprendizagem Significativa
Authors: Costa Felipe de Almeida , Allevato Norma Suely Gomes
Published: February 2019

Este artigo apresenta uma análise da produção de estudantes na resolução de uma situação-problema envolvendo funções trigonométricas. A atividade foi extraída do Caderno do Aluno, material elaborado pela Secretaria de Estado da Educação de São Paulo. Participaram da resolução estudantes do 2º ano do Ensino Médio de uma escola pública de São Paulo. O trabalho dos estudantes foi realizado em grupos.  O desenvolvimento da atividade envolvia um organizador prévio elaborado no GeoGebra e a consideração dos pesquisadores de que conhecimentos prévios estavam disponíveis na aquisição do conhecimento novo envolvido, subsidiados pela Teoria da Aprendizagem Significativa de David Ausubel. A situação envolveu questões relativas às funções y = Asen(Bx) + C e y = Acos(Bx) + C e teve por objetivo possibilitar o aprofundamento de conhecimentos sobre funções trigonométricas, mais especificamente a avaliação dos efeitos dos parâmetros A, B e C. As análises revelaram que, no uso de um software de geometria dinâmica, na condição de organizador prévio e com a existência de conhecimentos prévios, as funções y = sen(x) e y = cos(x) potencializam a aprendizagem dos estudantes acerca dos conhecimentos novos da situação-problema proposta.
Primiparous and Multiparous Sows Have Largely Similar Colostrum and Milk Composition Profiles Throughout Lactation
Authors: Craig Jessica R. , Dunshea Frank R. , Cottrell Jeremy J. , Wijesiriwardana Udani A. , Pluske John R.
Published: January 2019

It is important to understand the biological factors influencing the poorer lifetime performance of gilt progeny in comparison to sow progeny and determine whether this may be partially due to differences in lactation performance between primiparous and multiparous sows. It was hypothesized that primiparous sows would have lower levels of immunoglobulin G (IgG) in colostrum and milk compared to multiparous sows, and lower levels of other energetic components. Differences in colostrum and milk composition between ten primiparous and ten multiparous sows (parities 3 and 4) from a commercial herd were examined throughout lactation (day 0, 1, 2, 3, 7, 14, and 21). Overall, there were no (p ≥ 0.05) parity differences in total IgG, fat, protein, lactose, and net energy (NE) concentrations. Primiparous sows had higher lactose levels at day 2 (parity by timepoint interaction; p = 0.036) and lower NE at day 3 (p = 0.091), and multiparous sows had higher lactose levels at days 14 and 21. Results suggest that shortcomings of gilt progeny are unlikely due to insufficient nutrient levels in colostrum and milk, and more likely to reduced colostrum and milk intake and their capacity to digest and absorb each component.
Dietary Energy Levels Affect Growth Performance through Growth Hormone and Insulin-Like Growth Factor 1 in Yak (Bos grunniens)
Authors: Yang Chao , Zhang Jianbo , Ahmad Anum Ali , Bao Pengjia , Guo Xian , Long Ruijun , Ding Xuezhi , Yan Ping
Published: January 2019

The objective of this study was to investigate the effects of different dietary energy levels on serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as well as gene expression of their associated binding proteins and receptors in yak. Fifteen adult male yaks with BW of 276.1 ± 3.5 kg were allotted in three dietary groups and were fed with low (LE), medium (ME), and high energy (HE) level diet having different NEg of 5.5 MJ/kg, 6.2 MJ/kg, 6.9 MJ/kg, respectively. The effects of these treatments on ADG, BW, ADFI, and feed conversion ratio were significant (p < 0.05) throughout the experimental period. Serum GH concentration decreased (p < 0.05) with an increase in dietary energy level on d 30 and d 60. While IGF-1 concentration was higher (p < 0.05) in ME group, as compared to LE and HE groups on d 60. The expression level of growth hormone receptor (GHR) was decreased (p < 0.001) and IGF-1 was increased with the increase in the dietary energy level. The relative expression of insulin-like growth factor binding protein 3 (IGFBP-3) was higher (p < 0.001) in ME and HE groups, except the LE group. In conclusion, our findings provide a first insight into the combined effect of GH and IGF-1 in controlling the metabolism and productivity of yak. It also showed that medium energy level diet contributed to promote growth performance of yak during the cold season.
High-Power GaN-Based Vertical-Cavity Surface-Emitting Lasers with AlInN/GaN Distributed Bragg Reflectors
Authors: Kuramoto Masaru , Kobayashi Seiichiro , Akagi Takanobu , Tazawa Komei , Tanaka Kazufumi , Saito Tatsuma , Takeuchi Tetsuya
Published: January 2019

High-efficiency and high-power operation have been demonstrated for blue GaN-based vertical-cavity surface-emitting lasers (VCSELs) with AlInN/GaN distributed Bragg reflectors. The high-efficiency performance was achieved by introducing a novel SiO2-buried lateral index guide and adjusting the front mirror reflectivity. Lateral optical confinement has been shown to greatly lower the otherwise significant loss of transverse radiation exhibited by typical VCSELs based on GaN. Employing a long (10λ) cavity can also enhance the output power, by lowering the thermal resistance of the VCSEL and increasing the operating current associated with thermal rollover. This modification, in conjunction with optimized front mirror reflectivity and a buried SiO2 lateral index guide, results in a blue VCSEL (in the continuous wave mode with an 8 μm aperture at 20 °C) having a superior differential quantum efficiency value of 31% and an enhanced 15.7 mW output power. This unit also exhibits a relatively high output power of 2.7 mW at temperatures as high as 110 °C. Finally, a 5.5 μm aperture VCSEL was found to generate a narrow divergence (5.1°) single-lobe far field pattern when operating at an output power of approximately 5 mW.
An Evaluation of the Water Quality Characteristics of Shipboard Sewage Disposal and Usability Based on Water Quality Enhancement
Authors: Choi Young-Ik , Ji Hyeon-Jo , Shin Dae-Yeol , Mansoor Sana , Kwan Min-Ji , Lee Seung-Chul , Jung Jin-Hee , Jung Byung-Gil , Sung Nak-Chang , Wang Jei-Pil
Published: January 2019

International Maritime Organization recognizes vessel-induced pollution as a global issue. The designation of the Baltic Sea as the special uncontaminated area was the beginning of the regulations for preventing marine pollution. In this regard, a process is needed which meets the provisions of MEPC. 227(64) for the specificity and constrained conditions of vessels, removes both nitrogen and phosphorus, requires convenient operation and low construction cost and is little affected by the load variation of inflow. This study used an SBR(sequencing batch reactor) and MBR(membrane bioreactor) combined process to iterate the stirring and aeration process and maintained the ratio of raw wastewater parameters (C:N:P) to be 10:3:1 in order to assess the quality and future availability of ultimate outflow in each time period of the stirring and aeration process. The removal efficiencies of COD and T-N exceeded 90% and 93% respectively. However, a detailed mechanism will be identified by a further study on nitrogen removal issues like DO aeration condition, stirring duration, ORP and NO3. As the removal efficiency of T-P exceeded 95%, the SBR and MBR process formed anaerobic and aerobic conditions without a separate coagulation process for removing phosphorus, thereby enabling easy phosphorus release and uptake. The optimal stirring and aeration condition seems to be 70–50 min. A further study will be efficiently conducted by focusing on the water quality criteria of the Maritime Environment Protect Committee. 227 (64) for E. coli and chlorine and a detailed mechanism.
Harbor Extraction Based on Edge-Preserve and Edge Categories in High Spatial Resolution Remote-Sensing Images
Authors: He Jian , Guo Yongfei , Zhang Zeshu , Yuan Hangfei , Ning Yonghui , Shao Shuai
Published: January 2019

Efficient harbor extraction is essential due to the strategic importance of this target in economic and military construction. However, there are few studies on harbor extraction. In this article, a new harbor extraction algorithm based on edge preservation and edge categories (EC) is proposed for high spatial resolution remote-sensing images. In the preprocessing stage, we propose a local edge preservation algorithm (LEPA) to remove redundant details and reduce useless edges. After acquiring the local edge-preserve images, in order to reduce the redundant matched keypoints and improve the accuracy of the target candidate extraction method, we propose a scale-invariant feature transform (SIFT) keypoints extraction method based on edge categories (EC-SIFT): this method greatly reduces the redundancy of SIFT keypoint and improves the computational complexity of the target extraction system. Finally, the harbor extraction algorithm uses the Support Vector Machine (SVM) classifier to identify the harbor target. The experimental results show that the proposed algorithm effectively removes redundant details and improves the accuracy and efficiency of harbor target extraction.
Flame Front and Burned Gas Characteristics for Different Split Injection Ratios and Phasing in an Optical GDI Engine
Authors: Martinez Santiago , Merola Simona , Irimescu Adrian
Published: January 2019

Direct-injection in spark-ignition engines has long been recognized as a valid option for improving fuel economy, reducing CO2 emissions and avoiding knock occurrence due to higher flexibility in control strategies. However, problems associated with mixture formation are responsible for soot emissions, one of the most limiting factors of this technology. Therefore, the combustion process and soot formation were investigated with different injection strategies on a gasoline direct injection (GDI) engine. The experimental analysis was realized on an optically accessible single cylinder engine when applying single, double and triple injection strategies. Moreover, the effect of fuel delivery phasing was also scrutinized by changing the start of the injection during late intake- and early compression-strokes. The duration of injection was split in different percentages between two or three pulses, so as to obtain close to stoichiometric operation in all conditions. The engine was operated at fixed rotational speed and spark timing, with wide-open throttle. Optical diagnostics based on cycle resolved digital imaging was applied during the early and late stages of the combustion process. Detailed information on the flame front morphology and soot formation were obtained. The optical data were correlated to in-cylinder pressure traces and exhaust gas emission measurements. The results suggest that the split injection of the fuel has advantages in terms of reduction of soot formation and NOx emissions and a similar combustion performance with respect to the single injection timing. Moreover, an early injection resulted in higher rates of heat release and in-cylinder pressure, together with a reduction of soot formation and flame distortion. The double injection strategy with higher percentage of fuel injected in the first pulse and early second injection pulse showed the best results in terms of combustion evolution and pollutant emissions. For the operative condition studied, a higher time for mixture homogenization and split of fuel injected in the intake stroke shows the best results.
Sub-Mode Aerosol Volume Size Distribution and Complex Refractive Index from the Three-Year Ground-Based Measurements in Chengdu China
Authors: Zhang Chi , Zhang Ying , Li Zhengqiang , Wang Yongqian , Xu Hua , Li Kaitao , Li Donghui , Xie Yisong , Zhang Yang
Published: January 2019

Chengdu is a typical basin city of Southwest China with rare observations of remote sensing measurements. To assess the climate change and establish a region aerosol model, a deeper understanding of the separated volume size distribution (VSD) and complex refractive index (CRI) is required. In this study, we employed the sub-mode VSD and CRI in Chengdu based on the three years observation data to investigate the sub-mode characteristics and climate effects. The annual average fraction of the fine-mode aerosol optical depth (AODf) is 92%, which has the same monthly tendency as the total AOD. But the coarse-mode aerosol optical depth (AODc) has little variation in different months. There are four distinguishing modes of VSD in Chengdu; the median radii are 0.17 μm ± 0.05, 0.31 μm ± 0.12, 1.62 μm ± 0.45, 3.25 μm ± 0.99, respectively. The multi-year average and seasonal variations of fine- and coarse-mode VSD and CRI are also analyzed to characterize aerosols over this region. The fine-mode single scattering albedos (SSAs) are higher than the coarse-mode ones, which suggests that the coarse-mode aerosols have a stronger absorbing effect on solar light than the small-size aerosol particles in Chengdu.
Influence of Boreal Winter Intraseasonal Variation of Aleutian Low on Water Vapor Transport and Atmospheric Rivers
Authors: Xiong Yating , Chen Qiuyu , Ren Xuejuan
Published: January 2019

The Aleutian Low (AL) operates multiple time scales. The intraseasonal variation of AL is responsible for the subseasonal variability over the pan-North Pacific region. Atmospheric water vapor transport and atmospheric rivers (ARs) changes associated with the intraseasonal variation of AL are investigated over the North Pacific region for the winters of 1979–2014 in this study. The AL’s intraseasonal variation with a peak period of 40 days is identified. A total of 43 events that demonstrate the AL’s feature of strengthening and then weakening is picked and used for composition analysis. During the AL’s strengthening stage, eastward water vapor transport is dominant to the west of 150° W over the mid-basin. Meanwhile, poleward transport is dominant between 150–125° W. During the AL’s weakening stage, the eastward transport is weakened, and the poleward transport is concentrated over the center basin. Accompanied by the AL’s intraseasonal intensity oscillation, the frequency of ARs firstly increases, and then decreases over the ARs’ climatological mean body region over the North Pacific. The moisture source over the western North Pacific is hoarded during non-AR days, while the moisture sinks over the northeastern North Pacific during the AL’s strengthening stage, and the moisture sources over the center basin during the AL’s weakening stage converge during AR days. Hydroclimate effects on anomalies in precipitation over the west coast of North America are also analyzed.
Chemical Composition of Aerosol over the Arctic Ocean from Summer ARctic EXpedition (AREX) 2011–2012 Cruises: Ions, Amines, Elemental Carbon, Organic Matter, Polycyclic Aromatic Hydrocarbons, n-Alkanes, Metals, and Rare Earth Elements
Authors: Ferrero Luca , Sangiorgi Giorgia , Perrone Maria Grazia , Rizzi Cristiana , Cataldi Marco , Markuszewski Piotr , Pakszys Paulina , Makuch Przemysław , Petelski Tomasz , Becagli Silvia , Traversi Rita , Bolzacchini Ezio , Zielinski Tymon
Published: January 2019

During the summers of 2011 and 2012, two scientific cruises were carried out over the Arctic Ocean aiming at the determination of the aerosol chemical composition in this pristine environment. First, mass spectrometry was applied to study the concentration and gas/particle partitioning of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes. Experimental and modelled data of phase partitioning were compared: results demonstrated an equilibrium between gas and particle phase for PAHs, while n-alkanes showed a particle-oriented partitioning, due to the local marine origin of them, confirmed by the extremely low value of their carbon preference index. Moreover, the inorganic and organic ions (carboxylic acids and amines) concentrations, together with those of elemental carbon (EC) and organic matter (OM), were analyzed: 63% of aerosol was composed of ionic compounds (>90% from sea-salt) and the OM content was very high (30.5%; close to 29.0% of Cl−) in agreement with n-alkanes’ marine signature. Furthermore, the amines’ (dimethylamine, trimethylamine, diethylamine) concentrations were 3.98 ± 1.21, 1.70 ± 0.82, and 1.06 ± 0.56 p.p.t.v., respectively, fully in keeping with concentration values used in the CLOUD (Cosmics Leaving OUtdoor Droplet)-chamber experiments to simulate the ambient nucleation rate in a H2SO4-DMA-H2O system, showing the amines’ importance in polar regions to promote new particle formation. Finally, high resolution mass spectrometry was applied to determine trace elements, including Rare Earth Elements (REEs), highlighting the dominant natural versus anthropic inputs for trace metals (e.g., Fe, Mn, Ti vs. As, Cd, Ni) and possible signatures of such anthropic activity.
Consumption of Chlorogenic Acids through Coffee and Health Implications
Authors: Farah Adriana , de Paula Lima Juliana
Published: February 2019

Chlorogenic acids (CGA) are the main antioxidant compounds in the Western diet, due to their high concentrations in coffee associated with the high consumption of the beverage. Until about 10 years ago, like many other phenolic compounds, CGA were thought to be poorly absorbed in the human digestive system. Along the years, large amounts of information on the absorption and metabolism of these compounds have been unveiled, and today, it is known that, on average, about one third of the consumed CGA from coffee is absorbed in the human gastrointestinal tract, although large inter-individual variation exists. Considering results from in vitro animal and human studies, it is possible to conclude that the antioxidant and anti-inflammatory effects of coffee CGA are responsible for, at least to a certain extent, the association between coffee consumption and lower incidence of various degenerative and non-degenerative diseases, in addition to higher longevity.
Self-Silencing, but Not Sexual Relationship Power Associated with Condom Use for Black College-Aged Women
Authors: Stokes Lynissa R. , Brody Leslie R.
Published: January 2019

Black adolescent and young adult women in the United States experience a disproportionately higher rate of HIV infections than White and Hispanic adolescent and young adult women. Heterosexual sexual activity is the main route of infection for women, regardless of race or ethnicity. We examined two potential barriers to reducing Black adolescent and young adult women’s HIV risk: high levels of self-silencing and low levels of sexual relationship power. Data were collected on a small convenience sample of sexually active Black college-aged women (N = 57, Mage = 19.6, SD = 1.4) who answered questions about their current or most recent dating relationship. We found that higher levels of self-silencing were significantly related to lower condom use frequency and to a lower likelihood of reporting condom use at last sex. No significant associations were found between sexual relationship power and condom use (frequency or at last sex). Data from this study suggest that self-silencing, which involves putting the needs of others ahead of one’s own in order to avoid conflict in relationships, is an important variable to consider when examining potential risk factors for sexually transmitted HIV among Black college-aged women. Implications for future studies on HIV risk are reviewed.
Factors Affecting Contractors’ Bidding Decisions for Construction Projects in Saudi Arabia
Authors: Alsaedi Mohammad , Assaf Sadi , Hassanain Mohammad A. , Abdallah Abdullatif
Published: January 2019

One of the critical decisions taken by contractors is whether or not to bid for a project. This is due to the complexity and uncertainty surrounding this decision, which is influenced by many factors. Given the above challenge, this study aimed to uncover the critical factors affecting the contractors’ bidding decisions in Saudi Arabia-based construction projects. A questionnaire survey, which consisted of 31 factors, was distributed to first-, second- and third-grade contractors. In total, 67 responses were obtained. Median and relative importance index (RII) techniques were adopted for ranking the most critical factors. Based on the received responses, the top six critical factors were “size of the job”, “type of the job”, “company’s strength in the industry”, “designer/design quality”, “rate of return”, and “project cash flow”. The least significant factors were “job start time” and “labor environment (union/nonunion/cooperative)”. The findings of this study show a level of agreement among all contractors about the critical factors. The findings would benefit contractors and subcontractors by increasing their understanding of the major factors affecting the bidding decision process. Contractors armed with such valuable information will be better able to enhance their bidding decision-making process in terms of efficiency and effectiveness.
Ultimate Shear of RC Beams with Corroded Stirrups and Strengthened with FRP
Authors: Spinella Nino , Colajanni Piero , Recupero Antonino , Tondolo Francesco
Published: January 2019

Transverse reinforcement plays a key role in the response behavior of reinforced concrete beams. Therefore, corrosion of steel stirrups may change the failure mode of elements from bending to shear, leading to a brittle and catastrophic crisis. It is important to strengthen reinforced concrete beams with corroded stirrups to enhance the shear resistance. This paper presents a formulation, based on the modified compression field theory, to estimate the ultimate shear of reinforced concrete beams strengthened with FRP, because of stirrup corrosion. The detrimental effect of corrosion on steel stirrup yield strength was taken into account by introducing an empirical decay law. The effective strain of FRP reinforcement was adequately evaluated by considering both debonding and tensile stress rupture. The proposed model was validated against collected experimental results, showing a good ability to evaluate shear strength. Moreover, a numerical analysis was carried out to highlight the role of the key parameters predicting the ultimate shear.
Systematic Review of the Potential of MicroRNAs in Diffuse Large B Cell Lymphoma
Authors: Larrabeiti-Etxebarria Ane , Lopez-Santillan Maria , Santos-Zorrozua Borja , Lopez-Lopez Elixabet , Garcia-Orad Africa
Published: January 2019

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of invasive non-Hodgkin’s lymphoma (NHL). DLBCL presents with variable backgrounds, which results in heterogeneous outcomes among patients. Although new tools have been developed for the classification and management of patients, 40% of them still have primary refractory disease or relapse. In addition, multiple factors regarding the pathogenesis of this disease remain unclear and identification of novel biomarkers is needed. In this context, recent investigations point to microRNAs as useful biomarkers in cancer. The aim of this systematic review was to provide new insight into the role of miRNAs in the diagnosis, classification, treatment response and prognosis of DLBCL patients. We used the following terms in PubMed” ((‘Non-coding RNA’) OR (‘microRNA’ OR ‘miRNA’ OR ‘miR’) OR (‘exosome’) OR (‘extracellular vesicle’) OR (‘secretome’)) AND (‘Diffuse large B cell lymphoma’ OR ‘DLBCL’)” to search for studies evaluating miRNAs as a diagnosis, subtype, treatment response or prognosis biomarkers in primary DLBCL in human patient populations. As a result, the analysis was restricted to the role of miRNAs in tumor tissue and we did not consider circulating miRNAs. A total of thirty-six studies met the inclusion criteria. Among them, twenty-one were classified in the diagnosis category, twenty in classification, five in treatment response and nineteen in prognosis. In this review, we have identified miR-155-5p and miR-21-5p as miRNAs of potential utility for diagnosis, while miR-155-5p and miR-221-3p could be useful for classification. Further studies are needed to exploit the potential of this field.
Calcium Signaling in Brain Cancers: Roles and Therapeutic Targeting
Authors: Maklad Ahmed , Sharma Anjana , Azimi Iman
Published: January 2019

Calcium signaling, in addition to its numerous physiological roles, is also implicated in several pathological conditions including cancer. An increasing body of evidence suggest critical roles of calcium signaling in the promotion of different aspects of cancer, including cell proliferation, therapy resistance and metastatic-related processes. In many cases, this is associated with altered expression and/or activity of some calcium channels and pumps. Brain cancers have also been the subject of many of these studies. In addition to diverse roles of calcium signals in normal brain function, a number of proteins involved in calcium transport are implicated to have specific roles in some brain cancers including gliomas, medulloblastoma, neuroblastoma and meningioma. This review discusses research that has been conducted so far to understand diverse roles of Ca2+-transporting proteins in the progression of brain cancers, as well as any attempts to target these proteins towards a therapeutic approach for the control of brain cancers. Finally, some knowledge gaps in the field that may need to be further considered are also discussed.
A Simplified Genomic Profiling Approach Predicts Outcome in Metastatic Colorectal Cancer
Authors: Capalbo Carlo , Belardinilli Francesca , Raimondo Domenico , Milanetti Edoardo , Malapelle Umberto , Pisapia Pasquale , Magri Valentina , Prete Alessandra , Pecorari Silvia , Colella Mariarosaria , Coppa Anna , Bonfiglio Caterina , Nicolussi Arianna , Valentini Virginia , Tessitore Alessandra , Cardinali Beatrice , Petroni Marialaura , Infante Paola , Santoni Matteo , Filetti Marco , Colicchia Valeria , Paci Paola , Mezi Silvia , Longo Flavia , Cortesi Enrico , Marchetti Paolo , Troncone Giancarlo , Bellavia Diana , Canettieri Gianluca , Giannini Giuseppe
Published: January 2019

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy.
Histone Deacetylase Inhibitors and Phenotypical Transformation of Cancer Cells
Authors: Wawruszak Anna , Kalafut Joanna , Okon Estera , Czapinski Jakub , Halasa Marta , Przybyszewska Alicja , Miziak Paulina , Okla Karolina , Rivero-Muller Adolfo , Stepulak Andrzej
Published: January 2019

Histone deacetylase inhibitors (HDIs) are a group of potent epigenetic drugs which have been investigated for their therapeutic potential in various clinical disorders, including hematological malignancies and solid tumors. Currently, several HDIs are already in clinical use and many more are on clinical trials. HDIs have shown efficacy to inhibit initiation and progression of cancer cells. Nevertheless, both pro-invasive and anti-invasive activities of HDIs have been reported, questioning their impact in carcinogenesis. The aim of this review is to compile and discuss the most recent findings on the effect of HDIs on the epithelial-mesenchymal transition (EMT) process in human cancers. We have summarized the impact of HDIs on epithelial (E-cadherin, β-catenin) and mesenchymal (N-cadherin, vimentin) markers, EMT activators (TWIST, SNAIL, SLUG, SMAD, ZEB), as well as morphology, migration and invasion potential of cancer cells. We further discuss the use of HDIs as monotherapy or in combination with existing or novel anti-neoplastic drugs in relation to changes in EMT.
GFP-Fragment Reassembly Screens for the Functional Characterization of Variants of Uncertain Significance in Protein Interaction Domains of the BRCA1 and BRCA2 Genes
Authors: Caleca Laura , Colombo Mara , van Overeem Hansen Thomas , Lázaro Conxi , Manoukian Siranoush , Parsons Michael T. , Spurdle Amanda B. , Radice Paolo
Published: January 2019

Genetic testing for BRCA1 and BRCA2 genes has led to the identification of many unique variants of uncertain significance (VUS). Multifactorial likelihood models that predict the odds ratio for VUS in favor or against cancer causality, have been developed, but their use is conditioned by the amount of necessary data, which are difficult to obtain if a variant is rare. As an alternative, variants mapping to the coding regions can be examined using in vitro functional assays. BRCA1 and BRCA2 proteins promote genome protection by interacting with different proteins. In this study, we assessed the functional effect of two sets of variants in BRCA genes by exploiting the green fluorescent protein (GFP)-reassembly in vitro assay, which was set-up to test the BRCA1/BARD1, BRCA1/UbcH5a, and BRCA2/DSS1 interactions. Based on the findings observed for the validation panels of previously classified variants, BRCA1/UbcH5a and BRCA2/DSS1 binding assays showed 100% sensitivity and specificity in identifying pathogenic and non-pathogenic variants. While the actual efficiency of these assays in assessing the clinical significance of BRCA VUS has to be verified using larger validation panels, our results suggest that the GFP-reassembly assay is a robust method to identify variants affecting normal protein functioning and contributes to the classification of VUS.
Extracellular Vesicles as Transmitters of Hypoxia Tolerance in Solid Cancers
Authors: Zonneveld Marijke I. , Keulers Tom G. H. , Rouschop Kasper M. A.
Published: January 2019

Tumour hypoxia is a common feature of solid tumours that contributes to poor prognosis after treatment. This is mainly due to increased resistance of hypoxic cells to radio- and chemotherapy and the association of hypoxic cells with increased metastasis development. It is therefore not surprising that an increased hypoxic tumour fraction is associated with poor patient survival. The extent of hypoxia within a tumour is influenced by the tolerance of individual tumor cells to hypoxia, a feature that differs considerably between tumors. High numbers of hypoxic cells may, therefore, be a direct consequence of enhanced cellular capability inactivation of hypoxia tolerance mechanisms. These include HIF-1α signaling, the unfolded protein response (UPR) and autophagy to prevent hypoxia-induced cell death. Recent evidence shows hypoxia tolerance can be modulated by distant cells that have experienced episodes of hypoxia and is mediated by the systemic release of factors, such as extracellular vesicles (EV). In this review, the evidence for transfer of a hypoxia tolerance phenotype between tumour cells via EV is discussed. In particular, proteins, mRNA and microRNA enriched in EV, derived from hypoxic cells, that impact HIF-1α-, UPR-, angiogenesis- and autophagy signalling cascades are listed.
Switchable Access to Amines and Imines from Reductive Coupling of Nitroarenes with Alcohols Catalyzed by Biomass-Derived Cobalt Nanoparticles
Authors: Song Tao , Duan Yanan , Chen Xiufang , Yang Yong
Published: January 2019

Cobalt nanoparticles modified with N-doped hierarchical porous carbon derived from biomass are found to be a highly efficient, reusable heterogeneous catalyst for the coupling of nitroarenes with alcohols, selectively affording imines and amines via the borrowing hydrogen strategy for the first time. The product selectivity between imine and amine may be precisely tuned by simple alteration of the reaction conditions without changing the catalyst in one reaction system. In this study, a broad set of complex imines and amines was successfully synthesized in good to high yields with various functional groups tolerated for both nitroarenes and alcohols, highlighting the potentially practical utility of the protocol. This heterogeneous catalyst can be easily removed from the reaction medium by external magnet and can be reused at least four times without significant loss in activity and selectivity.
Metabolic Reprogramming in Breast Cancer and Its Therapeutic Implications
Authors: Gandhi Nishant , Das Gokul
Published: January 2019

Current standard-of-care (SOC) therapy for breast cancer includes targeted therapies such as endocrine therapy for estrogen receptor-alpha (ERα) positive; anti-HER2 monoclonal antibodies for human epidermal growth factor receptor-2 (HER2)-enriched; and general chemotherapy for triple negative breast cancer (TNBC) subtypes. These therapies frequently fail due to acquired or inherent resistance. Altered metabolism has been recognized as one of the major mechanisms underlying therapeutic resistance. There are several cues that dictate metabolic reprogramming that also account for the tumors’ metabolic plasticity. For metabolic therapy to be efficacious there is a need to understand the metabolic underpinnings of the different subtypes of breast cancer as well as the role the SOC treatments play in targeting the metabolic phenotype. Understanding the mechanism will allow us to identify potential therapeutic vulnerabilities. There are some very interesting questions being tackled by researchers today as they pertain to altered metabolism in breast cancer. What are the metabolic differences between the different subtypes of breast cancer? Do cancer cells have a metabolic pathway preference based on the site and stage of metastasis? How do the cell-intrinsic and -extrinsic cues dictate the metabolic phenotype? How do the nucleus and mitochondria coordinately regulate metabolism? How does sensitivity or resistance to SOC affect metabolic reprogramming and vice-versa? This review addresses these issues along with the latest updates in the field of breast cancer metabolism.
Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease
Authors: Mader Simone , Brimberg Lior
Published: January 2019

Aquaporin-4 (AQP4) is a water channel expressed on astrocytic endfeet in the brain. The role of AQP4 has been studied in health and in a range of pathological conditions. Interest in AQP4 has increased since it was discovered to be the target antigen in the inflammatory autoimmune disease neuromyelitis optica spectrum disorder (NMOSD). Emerging data suggest that AQP4 may also be implicated in the glymphatic system and may be involved in the clearance of beta-amyloid in Alzheimer’s disease (AD). In this review, we will describe the role of AQP4 in the adult and developing brain as well as its implication for disease.
Autophagy: Dual Response in the Development of Hepatocellular Carcinoma
Authors: Yazdani Hamza O. , Huang Hai , Tsung Allan
Published: January 2019

Autophagy is an evolutionary conserved intracellular mechanism which helps eukaryotic cells in maintaining their metabolic state to afford high-efficiency energy requirements. In the physiology of a normal liver and the pathogenesis of liver diseases, autophagy plays a crucial role. Autophagy has been found to be both upregulated and downregulated in different cancers providing the evidence that autophagy plays a dual role in suppressing and promoting cell survival. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the major leading cause of cancer mortality worldwide. In light of its high complexity and poor prognosis, it is essential to improve our understanding of autophagy’s role in HCC. In this review, we summarize the dual mechanism of autophagy in the development of HCC and elucidate the currently used therapeutic strategies for anti-HCC therapy.
Biology, Pathophysiological Role, and Clinical Implications of Exosomes: A Critical Appraisal
Authors: Jan Arif Tasleem , Rahman Safikur , Khan Shahanavaj , Tasduq Sheikh Abdullah , Choi Inho
Published: January 2019

Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are released into the extracellular milieu or body fluids; this process was reported for mesenchymal, epithelial, endothelial, and different immune cells (B-cells and dendritic cells), and was reported to be correlated with normal physiological processes. The compositions and abundances of exosomes depend on their tissue origins and cell types. Exosomes range in size between 30 and 100 nm, and shuttle nucleic acids (DNA, messenger RNAs (mRNAs), microRNAs), proteins, and lipids between donor and target cells. Pathogenic microorganisms also secrete exosomes that modulate the host immune system and influence the fate of infections. Such immune-modulatory effect of exosomes can serve as a diagnostic biomarker of disease. On the other hand, the antigen-presenting and immune-stimulatory properties of exosomes enable them to trigger anti-tumor responses, and exosome release from cancerous cells suggests they contribute to the recruitment and reconstitution of components of tumor microenvironments. Furthermore, their modulation of physiological and pathological processes suggests they contribute to the developmental program, infections, and human diseases. Despite significant advances, our understanding of exosomes is far from complete, particularly regarding our understanding of the molecular mechanisms that subserve exosome formation, cargo packaging, and exosome release in different cellular backgrounds. The present study presents diverse biological aspects of exosomes, and highlights their diagnostic and therapeutic potentials.
Characteristics of AISI 420 Stainless Steel Modified by Low-Temperature Plasma Carburizing with Gaseous Acetone
Authors: Liu Ruiliang , Yan Mufu
Published: January 2019

In this research work, low-temperature carburizing of AISI 420 martensitic stainless steel was conducted at 460 °C for different amounts of time using an acetone source. The microstructure and phase structure of the carburized layers were characterized by optical microscope and X-ray diffraction. The properties of the carburized layers were tested with a microhardness tester and an electrochemical workstation. The results indicate uniform layers are formed on martensitic stainless steel surfaces, and the carburized layers are mainly composed of carbon “expanded” α (αC) and Fe3C phases. The property tests indicated that after plasma–carburizing, the hardness of the stainless steel surface can reach up to 850 HV0.1. However, the corrosion resistance of stainless steel decreased slightly, and the corrosion characteristic of stainless steel was altered from pitting to general corrosion. The semiconductor characteristic of the passivation film on stainless steel was transformed from the p-type for untreated specimens to the n-type for carburized specimens.
Life under Continuous Streaming: Recrystallization of Low Concentrations of Bacterial SbpA in Dynamic Flow Conditions
Authors: Iturri Jagoba , Moreno-Cencerrado Alberto , Toca-Herrera José Luis
Published: January 2019

The well-known bacterial S-layer protein SbpA from Lysinibacillus sphaericus CCM2177 induces spontaneous crystal formation via cooperative self-assembly of the protein subunits into an ordered supramolecular structure. Recrystallization occurs in the presence of divalent cations (i.e., Ca2+) and finally leads to producing smooth 2-D crystalline coatings composed of squared (p4) lattice structures. Among the factors interfering in such a process, the rate of protein supply certainly plays an important role since a limited number of accessible proteins might turn detrimental for film completion. Studies so far have mostly focused on high SbpA concentrations provided under stopped-flow or dynamic-flow conditions, thus omitting the possibility of investigating intermediate states, in which dynamic flow is applied for more critical concentrations of SbpA (i.e., 25, 10, and 5 µg/mL). In this work, we have characterized both physico-chemical and topographical aspects of the assembly and recrystallization of SbpA protein in such low concentration conditions by means of in situ Quartz Crystal Microbalance with Dissipation (QCMD) and atomic force microscopy (AFM) measurements, respectively. On the basis of these experiments, we can confirm how the application of a dynamic flow influences the formation of a closed and crystalline protein film from low protein concentrations (i.e., 10 µg/mL), which otherwise would not be formed.
Coating Thickness Determination Using X-ray Fluorescence Spectroscopy: Monte Carlo Simulations as an Alternative to the Use of Standards
Authors: Giurlani Walter , Berretti Enrico , Innocenti Massimo , Lavacchi Alessandro
Published: January 2019

X-ray fluorescence is often employed in the measurement of the thickness of coatings. Despite its widespread nature, the task is not straightforward because of the complex physics involved, which results in high dependence on matrix effects. Thickness quantification is accomplished using the Fundamental Parameters approach, adjusted with empirical measurements of standards with known composition and thickness. This approach has two major drawbacks: (i) there are no standards for any possible coating and coating architecture and (ii) even relying on standards, the quantification of unknown samples requires the precise knowledge of the matrix nature (e.g., in the case of multilayer coatings the thickness and composition of each underlayer). In this work, we describe a semiquantitative approach to coating thickness measurement based on the construction of calibration curves through simulated XRF spectra built with Monte Carlo simulations. Simulations have been performed with the freeware software XMI-MSIM. We have assessed the accuracy of the methods by comparing the results with those obtained by (i) XRF thickness determination with standards and (ii) FIB-SEM cross-sectioning. Then we evaluated which parameters are critical in this kind of indirect thickness measurement.