bluuebunny/crossref_metadata_2025 huggingface dataset:
МЕТОДИЧНІ РЕКОМЕНДАЦІЇ ЩОДО ФОРМУВАННЯ У МАЙБУТНІХ ОФІЦЕРІВ-ПРИКОРДОННИКІВ ПРОФЕСІЙНОЇ КУЛЬТУРИ
Authors: Шумовецька С. П.
Published: February 2020

У статті висвітлено методичні рекомендації науково-педагогічним працівникам військового навчального закладу щодо формування у майбутніх офіцерів-прикордонників професійної культури. Детально розкрито особливості концепції і технології формування професійної культури та висвітлено основні напрями педагогічного виливу протягом чотирьох етапів: етапу ознайомлення, становлення, актуалізації та індивідуалізації.

Запропоновано на першому етапі звертати увагу на розвиток у майбутніх офіцерів-прикордонників мотивації до вивчення професійної культури, ознайомлювати їх з цінностями прикордонної служби та місією прикордонника, розвивати комунікативні уміння, необхідні для професійної комунікації з громадянами у пунктах пропуску через державний кордон. Відповідно до концепції на другому етапі рекомендовано розширювати кругозір курсантів, ознайомлювати їх з інтелектуальною історією України, забезпечити прилучення до європейських цінностей прикордонної служби, вдосконалювати навички міжособистісної взаємодії. Важливими напрямками роботи на третьому етапі визначено формування у курсантів навичок роботи з інформацією та протидії ворожій пропаганді, стимулювання пізнавальної активності засобами проблемних методів, інтенсифікацію інтелектуальної діяльності з використанням можливостей інформаційних технологій. На четвертому етапі рекомендовано ознайомити курсантів з історичними засадами прикордонної безпеки, формувати у них навички самостійного здобування професійних знань на основі проектних методів, поглиблювати за допомогою дослідницьких методів знання з проблематики лідерства та управління прикордонним підрозділом. Ці заходи допоможуть розвивати у курсантів здатності до ефективного виконання складних завдань професійної діяльності, вміння нестандартно мислити, що необхідно для їх практичної діяльності та адекватного реагування на ймовірні виклики та загрози прикордонній безпеці.

Ключові слова: професійна культура, офіцер-прикордонник, методичні рекомендації, концепція, технологія, педагогічні умови.
ВИКОРИСТАННЯ СОЦІАЛЬНО-КОМУНІКАЦІЙНИХ ТЕХНОЛОГІЙ У РОБОТІ З ЛЮДЬМИ ПОХИЛОГО ВІКУ
Authors: Вікторова Л. В. , Роганов М. М.
Published: February 2020

У статті розглядається проблема соціально-педагогічного супроводу людей похилого віку; розкриваються чинники (біологічні та соціально-психологічні), особливості та можливості цієї групи населення для активного життя в літньому віці; наголошується на самооцінці як фактору успішної адаптації людини в літньому віці та надається аналіз інтелектуальним особливостям людей похилого віку. Розкривається роль освіти як усвідомленого вибору літніми людьми тематики навчання, освоєння знань, умінь і цінностей; наголошується на тому, що незалежно від предмета вивчення, освіта в похилому віці допомагає адекватному сприйняттю людиною нової ролі у суспільстві й у власному житті, що допомагає реалістично оцінювати власні ресурси і можливості; також освоїти новий «інструментарій», що допомагає долати проблеми, які виникають в цій життєвій фазі. Наголошується на труднощах, що виникають при організації навчання літніх людей, зокрема, у підборі викладачів та у можливості використання ними андрагогічної майстерності; термінах проведення навчання; застосуванні новітніх технологій; підтримці (технічній, адмініст­ративній, організаційній); визначенні основних навичок і ключових компетенцій. Розкриваються зміст, методи і засоби використання сучасних інформаційно-комунікаційних технологій через масове залучення людей похилого віку до навчання навичкам роботи з комп’ютером та Інтернетом, а також забезпечення спілкування в соціальних мережах, блогах, форумах, для вдосконалення набутих ними знань, впевненого спілкування в мережах, залучення до життя у суспільстві та використання інформаційно-комунікаційних технологій в своєму повсякденному житті.

Ключові слова: геронтологія, людина похилого віку, освіта дорослих, інформаційно-комунікаційні технології, андрагогічна майстерність.
ЗМІСТ І СТРУКТУРА ВИХОВАННЯ КОМУНІКАТИВНОЇ ТОЛЕРАНТНОСТІ У МАЙБУТНІХ ВИХОВАТЕЛІВ
Authors: Єфименко Л. М.
Published: February 2020

У статті обґрунтовано актуальність проблеми виховання комунікативної толерантності у майбутніх вихователів як одне з найважливіших завдань нашого суспільства, а також системи освіти. Проаналізовано зміст поняття «комунікативна толерант­ність» на основі досліджень різних науковців (В. Бойко, Є. Гребе­нець, Є. Касьянова, А. Ніколаєва, О. Романчук, А. Скок). У якості основного змісту досліджуваного поняття автори називають такі ключові елементи, як: «характеристика ставлення особистості до людей», «здатність людини до взаємодії з іншими» тощо.

Визначено, що комунікативна толерантність вихователя дошкільного закладу – це професійно значуща якість особистості, що підпорядковується завданням, змісту, характеру його діяльності та проявляється у встановленні ефективних комунікативних взаємин з суб’єктами педагогічного процесу.

Наголошено на тому, що виховання комунікативної толерантності майбутніх фахівців дошкільної освіти – це організований педагогічний процес, спрямований на особистісний розвиток студентів, удосконалення їх індивідуальних особливостей, що виявляються в міжособистісних взаєминах та діяльності.

 Установлено, що комунікативна толерантність майбутніх вихователів має передбачати наявність емпатії, доброти, терпимості, спілкування, поваги, довіри, витримки, доброзичли­вості, самоконтролю, емоційної стійкості у різних ситуаціях.

У результаті аналізу наукової літератури з’ясовано, що до компонентів комунікативної толерантності майбутніх вихователів дошкільного закладу доцільно віднести когнітивний, емоційний, мотиваційно-ціннісний

Ключові слова: толерантність, комунікативна толерантність, спілкування, комунікація, зміст, структура, компоненти.
Reaching and Teaching Students in Poverty
Authors: Goff Maria Hernandez
Published: February 2020

The second edition of Reaching and Teaching Students in Poverty: Strategies for Erasing the Opportunity Gap aims to move educators from a deficit view of students experiencing poverty to a structural view by examining the structural inequalities in the United States. This book encourages educators to develop equity literacy and provides twelve principles of equity literacy, supported by historical data and current research, to guide readers in this process. The book also offers actionable strategies to implement at the classroom, school, and district level.
Emtia Finansallaşmasına Borsa İstanbul ve Petrol Bağıntısı Açısından Bir Bakış
Authors: ORDU AKKAYA Beyza Mina
Published: February 2020

Kurumsal finansal yatırımcıların 2000’li yılların başı ile birlikte emtia piyasalarına yoğun biçimde yatırım yapması yeni bir olguyu doğurmuş ve bu olgu emtianın finansallaşması olarak adlandırılmıştır. Finansallaşma hipotezini savunanlar, aynı anda birçok piyasaya yatırım yapan kurumsal yatırımcıların,
piyasalar arasındaki bağıntıyı kuvvetlendirdiğini iddia ederler. Öte yandan; bir diğer grup ise artan bağıntının konjonktürel olduğunu ve 2008 krizinden sonra küresel ekonomideki yavaşlık olduğunu ifade eder. Bu çalışmada Borsa İstanbul’a (BIST) gelen haftalık yabancı yatırım portföy yatırım tutarı kullanılarak,
finansallaşma olgusu BIST ve petrol fiyatları özelinde incelenmiştir. Öncelikle, BIST100 endeksi ve WTI Cushing petrol fiyatları arasındaki asimetrik zamana bağlı koşullu korelasyon hesaplanmış, sonra bu korelasyonun yabancı portföy yatırımı ile mi yoksa konjonktürel olarak mı arttığı kantil regresyon kullanarak
incelenmiştir. Sonuçlar, finansallaşmayı desteklememekle birlikte; aksine artan bağıntının konjonktürel olduğunu göstermektedir.
Eleştirel Yönetim Çalışmaları Fildişi Kulesinden Nasıl Çıkabilir? Eleştirel Edimsellik ve Topluluk Ekonomileri
Authors: ASLAN Alper
Published: February 2020

Son yıllarda eleştirel yönetim çalışmaları kendi akademik fildişi kulesinden çıkararak gündelik yaşamda etkili olmak istemektedir. Bunun nasıl olacağı “eleştirel edimsellik” kavramıyla tartışılmaktadır. Eleştirel edimsellik soyut ve büyük çaplı özgürleşmelerin peşinden koşulmasına karşıdır; o kurumsal iktidar
ilişkilerindeki küçük kazanımları arar. Ancak küçük kazanımlar kapitalist kimlikler ve pratikleri korur; böylece eleştirel edimsellik ana-akım yönetim ve örgüt çalışmalarına benzer. Bu yüzden, birçok araştırmacı eleştirel edimselliğin siyasal amaçlarını eleştirir. Ayrıca, eleştirel edimsellik ürettiği eleştirinin etkili olabilmesi yolunda
gerçekçi ve yeterli maddesel koşulları ele almamaktadır; genellikle, yöneticilerin ana-akım söylemlerini değiştirmeye odaklanır. Bu araştırma, eleştirel edimselliğin topluluk ekonomilerinden yararlanması gerektiğini belirtmiştir. Topluluk ekonomileri, kapitalizmin gücünü vurgulayan sermaye merkezciliğe karşıdır; etik-siyasi
etkileşimlerle gayri-kapitalist özneler ve örgütlenmeler oluşturmaya dayanır. Bu bağlamda, topluluk ekonomileri siyasal ve maddesel olarak eleştirel edimselliğe yol gösterebilecektir.
RETRACTED: Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras/PLCε/PKCε Signaling Pathway
Authors: Liu Jiayu , Zheng Yongbo , Gao Yingying , Quan Zhen , Qiao Bo , Li Luo , Li Ting , Duan Limei , Yang Jinxiao , Luo Chunli , Wu Xiaohou
Published: February 2020

Castration-resistant prostate cancer (CRPC) is a progressed stage of prostate cancer, which requires better understanding of the mechanisms and remains an unmet clinical need. As a common oncogene, K-Ras is associated with malignant behavior in different types of tumors but its role in CRPC is unknown. The present study aims to find the mechanism of K-Ras in CRPC and whether it can be used as a crucial molecule for the treatment of CRPC. For this purpose, tissue samples from primary prostate cancer (PPC) and CRPC patients were analyzed by immunohistochemistry and the data showed that K-Ras was elevated in CRPC. More importantly, higher K-Ras expression was related to a shorter recurrence-free survival time in patients with CRPC. In addition, K-Ras promoted the invasion, migration, and drug resistance of CRPC cells by activation of PLCε/PKCε signaling pathway. Meanwhile, the inhibitor of K-RasG12C mutants was able to inhibit malignant behavior of CRPC cells in vitro and in vivo. Inhibitors of K-RasG12C mutants have entered clinical trials. Taken together, the study shows that K-Ras may activate PKCε through PLCε, resulting in the alterations of malignant behavior of CRPC. Inhibitor 9, an inhibitor of the K-RasG12C mutant, has a strong anti-tumor effect in CRPC, which potentially suggests that inhibitors of this nature may serve as a promising treatment for CRPC.
Image Interpretability of nSight-1 Nanosatellite Imagery for Remote Sensing Applications
Authors: Mhangara Paidamwoyo , Mapurisa Willard , Mudau Naledzani
Published: February 2020

Nanosatellites are increasingly being used in space-related applications to demonstrate and test scientific capability and engineering ingenuity of space-borne instruments and for educational purposes due to their favourable low manufacturing costs, cheaper launch costs, and short development time. The use of CubeSat to demonstrate earth imaging capability has also grown in the last two decades. In 2017, a South African company known as Space Commercial Services launched a low-orbit nanosatellite named nSight-1. The demonstration nanosatellite has three payloads that include a modular designed SCS Gecko imaging payload, FIPEX atmospheric science instrument developed by the University of Dresden and a Radiation mitigation VHDL coding experiment supplied by Nelson Mandela University. The Gecko imager has a swath width of 64 km and captures 30 m spatial resolution images using the red, green, and blue (RGB) spectral bands. The objective of this study was to assess the interpretability of nSight-1 in the spatial dimension using Landsat 8 as a reference and to recommend potential earth observation applications for the mission. A blind image spatial quality evaluator known as Blind/Referenceless Image Spatial Quality Evaluator (BRISQUE) was used to compute the image quality for nSight-1 and Landsat 8 imagery in the spatial domain and the National Imagery Interpretability Rating Scale (NIIRS) method to quantify the interpretability of the images. A visual interpretation was used to propose some potential applications for the nSight1 images. The results indicate that Landsat 8 OLI images had significantly higher image quality scores and NIIRS results compared to nSight-1. Landsat 8 has a mean of 19.299 for the image quality score while nSight-1 achieved a mean of 25.873. Landsat 8 had NIIRS mean of 2.345 while nSight-1 had a mean of 1.622. The superior image quality and image interpretability of Landsat could be attributed for the mature optical design on the Landsat 8 satellite that is aimed for operational purposes. Landsat 8 has a GDS of 30-m compared to 32-m on nSight-1. The image degradation resulting from the lossy compression implemented on nSight-1 from 12-bit to 8-bit also has a negative impact on image visual quality and interpretability. Whereas it is evident that Landsat 8 has the better visual quality and NIIRS scores, the results also showed that nSight-1 are still very good if one considers that the categorical ratings consider that images to be of good to excellent quality and a NIIRS mean of 1.6 indicates that the images are interpretable. Our interpretation of the imagery shows that the data has considerable potential for use in geo-visualization and cartographic land use and land cover mapping applications. The image analysis also showed the capability of the nSight-1 sensor to capture features related to structural geology, geomorphology and topography quite prominently.
A 1Ns Disomic Addition from Psathyrostachys Huashanica Keng Confers Resistance to Powdery Mildew in Wheat
Authors: Han Jing , Liu Yuxiu , Hou Chenchen , Li Jiachuang , Wang Jinglin , Zhang Qiaoying , Yang Qunhui , Chen Xinhong , Wu Jun
Published: February 2020

Powdery mildew is a fungal disease that threatens wheat production throughout the world. Breeding resistant cultivars is an effective way to reduce harm caused by powdery mildew. In this study, 35 wheat-Psathyrostachys huashanica-derived lines were developed by crossing common wheat and P. huashanica Keng (2n = 2x = 14, NsNs) using embryo culture. Resistance to powdery mildew in the derived lines was identified at the seedling and adult stages. Line H5-5-4-2 was selected with immunity to powdery mildew at both growth stages. The chromosome structure of this line was characterized by cytology, genomic in situ hybridization (GISH), and expressed sequence tag-sequence-tagged site (EST-STS) analysis. The chromosome configuration was 2n = 44 = 22II. Two P. huashanica chromosomes with strong hybridization signals were detected by GISH analysis. Among 83 EST-STS markers that covered all seven homologous groups in wheat, three pairs of STS markers, BE497584, BF202643, and BG262410, located in wheat homologous group 1 amplified clear specific bands related to P. huashanica. The results indicated that resistant line H5-5-4-2 was a wheat-P. huashanica 1Ns disomic addition line.
Nitrogen and Phosphorus Absorption and Yield of Tomato Increased by Regulating the Bacterial Community under Greenhouse Conditions via the Alternate Drip Irrigation Method
Authors: Wang Jingwei , Niu Wenquan , Li Yuan
Published: February 2020

Alternate drip irrigation (ADI) is a useful irrigation method for water conservation and the regulation of soil quality; however, knowledge about the underlying mechanism of soil-root-bacterium interactions is limited. To determine the mechanism by which ADI transforms soil nutrients and thereby promotes plant growth and to provide a basis for the reasonable selection of drip irrigation methodology, the present study investigated the effects of ADI on the composition and potential function of the bacterial community in tomato rhizosphere soils under greenhouse conditions and analyzed the soil-root-bacterium interactions under ADI. The results revealed that, compared with the soils of the plots treated with surface drip irrigation with plastic film mulching (DI-PFM), the soils of the plots treated with ADI presented an optimized bacterial community structure and optimized soil nitrogen (N) and phosphorus (P) metabolism. The soil available N contents under ADI with lower irrigation limits of 50%, 60%, and 70% of field capacity (A50, A60, and A70 treatments, respectively) were 1.48, 2.19, and 1.91 times greater than those under DI-PFM, respectively; similarly, the soil available P contents were 1.49, 1.65, and 2.91 times greater; the total phosphorus (TP) contents in the tomato roots were 1.06, 1.94, and 1.59 times greater, respectively; and the TP contents in the tomato plants were 1.03, 1.75, and 2.84 times greater, respectively. In addition, the total nitrogen (TN) contents in the tomato roots under ADI with lower irrigation limits of 60% and 70% of field capacity were 1.07 and 1.14 times greater than those under DI-PFM, and the TN contents in the tomato stems were 1.21 and 1.12 times greater than those under DI-PFM. However, compared with DI-PFM, ADI improved tomato yields by 24.23% under only 70% of field capacity. Therefore, ADI significantly enhanced soil-root interactions and stimulated the activation of soil N and P, but only a proper low soil moisture content (SMC) led to significantly increased tomato yields.
Answers to the Frequently Asked Questions Regarding Horse Feeding and Management Practices to Reduce the Risk of Atypical Myopathy
Authors: Votion Dominique-Marie , François Anne-Christine , Kruse Caroline , Renaud Benoit , Farinelle Arnaud , Bouquieaux Marie-Catherine , Marcillaud-Pitel Christel , Gustin Pascal
Published: February 2020

In 2014, atypical myopathy (AM) was linked to Acer pseudoplatanus (sycamore maple) in Europe. The emergence of this seasonal intoxication caused by a native tree has raised many questions. This manuscript aims at answering the five most frequently asked questions (FAQs) regarding (1) identification of toxic trees; reduction of risk at the level of (2) pastures and (3) equids; (4) the risk associated with pastures with sycamores that have always been used without horses being poisoned and (5) the length of the risk periods. Answers were found in a literature review and data gathered by AM surveillance networks. A guide is offered to differentiate common maple trees (FAQ1). In order to reduce the risk of AM at pasture level: Avoid humid pastures; permanent pasturing; spreading of manure for pasture with sycamores in the vicinity and avoid sycamore maple trees around pasture (FAQ2). To reduce the risk of AM at horse level: Reduce pasturing time according to weather conditions and to less than six hours a day during risk periods for horses on risk pasture; provide supplementary feeds including toxin-free forage; water from the distribution network; vitamins and a salt block (FAQ3). All pastures with a sycamore tree in the vicinity are at risk (FAQ4). Ninety-four percent of cases occur over two 3-month periods, starting in October and in March, for cases resulting from seeds and seedlings ingestion, respectively (FAQ5).
Biochanin A Inhibits Ruminal Nitrogen-Metabolizing Bacteria and Alleviates the Decomposition of Amino Acids and Urea In Vitro
Authors: Liu Sijia , Zhang Zhenyu , Hailemariam Samson , Zheng Nan , Wang Min , Zhao Shengguo , Wang Jiaqi
Published: February 2020

Biochanin A is a naturally occurring flavonoid compound that is found in plant species such as red clover (Trifolium pretense) and alfalfa (Medicago sativa). Flavonoids have been reported to regulate ruminal fermentation, and the objective of this study was to evaluate the effects of biochanin A on ruminal microbial composition and nitrogen metabolism. The experiment was performed by in vitro batch culturing of a control (without biochanin A) and a biochanin A treatment. Following a 24-h incubation, gas production and the amounts of ammonia-nitrogen (NH3-N), volatile fatty acid (VFA), and amino acids were measured. Microbial population using 16S rRNA gene sequence. We found that the addition of biochanin A significantly increased microbial gas production; but had no effect on VFA production. Biochanin A supplementation also resulted in reduced microbial urease activity with half the maximal inhibitory concentration of 320 nM and also inhibited the degradation rates of total amino acids, valine, lysine, methionine and leucine by 18%, 56%, 37%, 13%, and 12%, respectively. This inhibition of urease activity and amino acid decomposition resulted in a significant reduction in the NH3-N concentration. High-throughput sequencing of the 16S rRNA sequence to monitor microbial composition showed that biochanin A significantly reduced the abundance of the proteolytic bacteria Prevotella and ureolytic bacteria Selenomonas, but increased the abundance of the lactic acid metabolizing bacteria Veillonella and Megasphaera. In conclusion, biochanin A reduced the production of ammonia by inhibiting proteolytic bacteria and their decomposition of urea and amino acids.
Multidrug-Resistant ESBL/AmpC-Producing Klebsiella pneumoniae Isolated from Healthy Thoroughbred Racehorses in Japan
Authors: Sukmawinata Eddy , Uemura Ryoko , Sato Wataru , Thu Htun Myo , Sueyoshi Masuo
Published: February 2020

Extended-spectrum β-lactamase (ESBL)- and AmpC β-lactamase (AmpC)-producing Klebsiella spp. have become a major health problem, leading to treatment failure in humans and animals. This study aimed to evaluate the presence of ESBL/AmpC-producing Klebsiella spp. isolated from racehorses in Japan. Feces samples from 212 healthy Thoroughbred racehorses were collected from the Japan Racing Association Training Centers between March 2017 and August 2018. ESBL/AmpC-producing Klebsiella spp. were isolated using selective medium containing 1 µg/mL cefotaxime. All isolates were subjected to bacterial species identification (MALDI-TOF MS), antimicrobial susceptibility test (disk diffusion test), characterization of resistance genes (PCR), conjugation assay, and genetic relatedness (multilocus sequence typing/MLST). Twelve ESBL/AmpC-producing Klebsiella pneumoniae (ESBL/AmpC-KP) were isolated from 3.3% of horse samples. Antimicrobial resistance profiling for 17 antimicrobials showed all ESBL/AmpC-KP were multidrug-resistant (MDR). Only 1 isolate was confirmed as an ESBL producer (blaCTX-M-2-positive), whereas the other 11 isolates were plasmid-mediated AmpC (pAmpC) producers (blaCMY positive). On the basis of MLST analysis, the ESBL-KP isolate was identified as sequence type (ST)-133 and four different STs among AmpC-KP isolates, ST-145, ST-4830, ST-4831, and ST-4832, were found to share six of the seven loci constituting a single-locus variant. This is the first study to show K. pneumoniae carrying MDR pAmpC isolated from a racehorse.
Experimental Investigations on the Effects of Fatigue Crack in Urban Metro Welded Bogie Frame
Authors: Wang Wenjing , Bai Jinyi , Wu Shengchuan , Zheng Jing , Zhou Pingyu
Published: February 2020

The welded bogie frame is the critical safety part of the urban metro vehicle. This paper focuses on finding out the factors inducing the fatigue cracks initiated from the positioning block weld toe of metro bogie frame. Fracture morphology and metallographic analysis were conducted to identify the failure modes, and on-track tests about the dynamic stress at the positioning block weld toe and vibration acceleration were performed. The typical signals of dynamic stress and acceleration were analyzed from time and frequency domain. The relationship between wheel polygon, rail corrugation, running speed and dynamic stress in amplitude and frequency are investigated in details. Research results show that the micro cracks induced by welding at the weld toe of positioning block propagate to the spring sleeve under relatively high alternating dynamic stress, which is strongly influenced by the wheel polygon, rail corrugation and the train running speed.
A Novel P300 Classification Algorithm Based on a Principal Component Analysis-Convolutional Neural Network
Authors: Li Feng , Li Xiaoyu , Wang Fei , Zhang Dengyong , Xia Yi , He Fan
Published: February 2020

Aiming at enhancing the classification accuracy of P300 Electroencephalogram signals in a non-invasive brain–computer interface system, a novel P300 electroencephalogram signals classification algorithm is proposed which is based on improved convolutional neural network. In the data preprocessing part, the proposed P300 classification algorithm used the Principal Component Analysis algorithm to not only remove the noise and artifacts in the data, but also increase the data processing speed. Furthermore, the proposed P300 classification algorithm employed the parallel convolution method to improve the traditional convolutional neural network framework, which can increase the network depth and improve the network’s ability to classify P300 electroencephalogram signals. The proposed algorithm was evaluated by two datasets (the dataset from the competition and the dataset from the laboratory). The results show that, in the dataset I, the proposed P300 classification algorithm could obtain accuracy rates higher than 95%, and achieve one of the best performances in four classification algorithms, while, in the dataset II, the proposed P300 classification algorithm can get accuracy rates higher than 90%, and is superior to the other three algorithms in all ten subjects. These demonstrated the effectiveness of the proposed algorithm. The proposed classification algorithm can be applied in the actual brain–computer interface systems to help people with disability in the daily lives.
Three-Dimensional Characterization of Peripapillary Retinal Pigment Epithelium-Basement Membrane Layer in Patients following Lumbar Puncture
Authors: Tong Junfei , Dong Pengfei , Kedar Sachin , Ghate Deepta , Gu Linxia
Published: February 2020

Purpose: To develop and test an innovative semi-automatic method for quantifying the three-dimensional morphology of the peripapillary retinal pigment epithelium-basement membrane (ppRPE/BM) layer, with application to lumbar puncture (LP) patients. Methods: Nineteen patients undergoing LP were recruited. The optic nerve head images of both eyes were acquired in 12 radial directions using optical coherence tomography (OCT) before and after LP. For each OCT image, the ppRPE/BM layer was automatically segmented with manual corrections by independent graders when necessary. The linear regression model of the ppRPE/BM layer was fitted using the least squares approach, and the ppRPE/BM layer angle was measured as the slope of the linear regression line. The Bland–Altman plots and intraclass correlations (ICC) were used to assess the inter-observer reliabilities in measuring the ppRPE/BM layer angle. The repeated measures ANOVA analysis was applied to determine whether the ppRPE/BM layer angle changes following LP varied across the radial directions. Results: The percentages of scans that required manual corrections were 24% and 32% in the right eyes and left eyes, respectively. The Bland–Altman plots and ICC demonstrated excellent inter-observer reliability. The ppRPE/BM layer angle varied significantly across the 12 radial OCT scanning directions both before and after LP. However, the LP-induced changes in the ppRPE/BM layer angle across different radial directions were not statistically significant (p-value > 0.01). Conclusions: The three-dimensional quantifications of the ppRPE/BM layer angles, enabled by the semi-automatic method, provided enhanced information of the optic nerve head structure. For LP patients, the ppRPE/BM layer angle changes following the LP did not vary significantly across various radial directions, indicating that it could be evaluated in any radial direction.
Filling History, Consolidating the Origins. The First Female Architects of the Barcelona School of Architecture (1964–1975)
Authors: Muxí Zaida , Arias Laurino Daniela
Published: February 2020

After Francisco Franco’s death, the process of democratisation of public institutions was a key factor in the evolution of the architectural profession in Spain. The approval of the creation of neighbourhood associations, the first municipal governments, and the modernisation of Spanish universities are some examples of this. Moreover, feminist and environmental activism from some parts of Spanish society was relevant for socio-political change that affected women in particular. The last decade of Franco’s Regime coincided with the first generation of women that graduated from the Barcelona School of Architecture (ETSAB). From 1964 to 1975, 73 female students graduated as architects—the first one was Margarita Brender Rubira (1919–2000) who validated her degree obtained in Romania in 1962. Some of these women became pioneers in different fields of the architectural profession, such as Roser Amador in architectural design, Alrun Jimeno in building technologies, Anna Bofill in urban design and planning, Rosa Barba in landscape architecture or Pascuala Campos in architectural design, and teaching with gender perspective. This article presents the contributions of these women to the architecture profession in relation to these socio-political advances. It also seeks—through the life stories, personal experiences, and personal visions on professional practice—to highlight those ‘other stories’ that have been left out of the hegemonic historiography of Spanish architecture.
Introduction of the Intermeshed Steel Connection—A New Universal Steel Connection
Authors: Al-Sabah Salam , Laefer Debra F. , Truong Hong Linh , Phuoc Huynh Minh , Le Jia-Liang , Martin Tony , Matis Pantelis , McGetrick Patrick , Schultz Arturo , Shemshadian Mohammad E. , Dizon Roseanne
Published: February 2020

Digital manufacturing has transformed many industries but has had only a limited impact in the construction sector. To capitalize on advanced manufacturing techniques, this paper introduces a radically new connection approach for gravity structural steel frames. The proposed intermeshed steel connection (ISC) exploits robotic abilities to cut structural steel member ends precisely to accelerate deployment and offer better disassembly options over existing approaches. Forces are transferred through common bearing surfaces at multiple contact points, and connections can be secured by small locking pieces. This paper introduces the geometry, manufacturing, and initial analysis and test results of the connection. The paper demonstrates the ability of the connection to (1) be manufactured within current industrial tolerances, (2) be erected and disassembled, and (3) perform at expected design levels.
Bone Morphogenetic Protein 4 Targeting Glioma Stem-Like Cells for Malignant Glioma Treatment: Latest Advances and Implications for Clinical Application
Authors: Nayak Sonali , Mahenthiran Ashorne , Yang Yongyong , McClendon Mark , Mania-Farnell Barbara , James Charles David , Kessler John A. , Tomita Tadanori , Cheng Shi-Yuan , Stupp Samuel I. , Xi Guifa
Published: February 2020

Malignant gliomas are heterogeneous neoplasms. Glioma stem-like cells (GSCs) are undifferentiated and self-renewing cells that develop and maintain these tumors. These cells are the main population that resist current therapies. Genomic and epigenomic analyses has identified various molecular subtypes. Bone morphogenetic protein 4 (BMP4) reduces the number of GSCs through differentiation and induction of apoptosis, thus increasing therapeutic sensitivity. However, the short half-life of BMP4 impedes its clinical application. We previously reviewed BMP4 signaling in central nervous system development and glioma tumorigenesis and its potential as a treatment target in human gliomas. Recent advances in understanding both adult and pediatric malignant gliomas highlight critical roles of BMP4 signaling pathways in the regulation of tumor biology, and indicates its potential as a therapeutic molecule. Furthermore, significant progress has been made on synthesizing BMP4 biocompatible delivery materials, which can bind to and markedly extend BMP4 half-life. Here, we review current research associated with BMP4 in brain tumors, with an emphasis on pediatric malignant gliomas. We also summarize BMP4 delivery strategies, highlighting biocompatible BMP4 binding peptide amphiphile nanostructures as promising novel delivery platforms for treatment of these devastating tumors.
Hypoxia-Induced Centrosome Amplification Underlies Aggressive Disease Course in HPV-Negative Oropharyngeal Squamous Cell Carcinomas
Authors: Mittal Karuna , Choi Da Hoon , Wei Guanhao , Kaur Jaspreet , Klimov Sergey , Arora Komal , Griffith Christopher C. , Kumar Mukesh , Imhansi-Jacob Precious , Melton Brian D. , Bhimji-Pattni Sonal , Osan Remus M. , Rida Padmashree , Golusinski Paweł , Aneja Ritu
Published: February 2020

Human papillomavirus-negative (HPV-neg) oropharyngeal squamous cell carcinomas (OPSCCs) are associated with poorer overall survival (OS) compared with HPV-positive (HPV-pos) OPSCCs. The major obstacle in improving outcomes of HPV-neg patients is the lack of robust biomarkers and therapeutic targets. Herein, we investigated the role of centrosome amplification (CA) as a prognostic biomarker in HPV-neg OPSCCs. A quantitative evaluation of CA in clinical specimens of OPSCC revealed that (a) HPV-neg OPSCCs exhibit higher CA compared with HPV-pos OPSCCs, and (b) CA was associated with poor OS, even after adjusting for potentially confounding clinicopathologic variables. Contrastingly, CA was higher in HPV-pos cultured cell lines compared to HPV-neg ones. This divergence in CA phenotypes between clinical specimens and cultured cells can therefore be attributed to an inaccurate recapitulation of the in vivo tumor microenvironment in the cultured cell lines, namely a hypoxic environment. The exposure of HPV-neg OPSCC cultured cells to hypoxia or stabilizing HIF-1α genetically increased CA. Both the 26-gene hypoxia signature as well as the overexpression of HIF-1α positively correlated with increased CA in HPV-neg OPSCCs. In addition, we showed that HIF-1α upregulation is associated with the downregulation of miR-34a, increase in CA and expression of cyclin- D1. Our findings demonstrate that the evaluation of CA may aid in therapeutic decision-making, and CA can serve as a promising therapeutic target for HPV-neg OPSCC patients.
Efficacy of Crizotinib, Ceritinib, and Alectinib in ALK-Positive Non-Small Cell Lung Cancer Treatment: A Meta-Analysis of Clinical Trials
Authors: Hoang Tung , Myung Seung-Kwon , Pham Thu Thi , Park Boyoung
Published: February 2020

This study aimed to evaluate the efficacy of anaplastic lymphoma kinase (ALK)-inhibitors in the treatment of ALK-positive non-small cell lung cancer (NSCLC) by using a meta-analysis of clinical trials. We searched PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov by using keywords related to the topic in August 2018. The pooled effect sizes were calculated based on a random-effects model. We also performed subgroup meta-analysis by types of ALK inhibitors (crizotinib, ceritinib, and alectinib). A total of 20 clinical trials with 10 single-arm trials and 10 double-arm trials were included in the final meta-analysis. The median overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), 1 year survival rate, and 2 year survival rate were 19.14 months, 8.47 months, 62%, 78%, 74%, and 62%, respectively. ALK inhibitors showed a significantly superior efficacy compared with chemotherapy (hazard ratio (HR) for OS, 0.83; HR for PFS, 0.43; rate difference (RD) for ORR, 0.23; and RD for DCR, 0.10). The current meta-analysis of clinical trials showed the significant efficacy of ALK inhibitors in the treatment of ALK-positive NSCLC. Further head-to-head trials are needed to compare their efficacy with other types of NSCLC treatment regimens. PROSPERO registration: CRD42018085987.
Asbestos and Intrahepatic Cholangiocarcinoma
Authors: Brandi Giovanni , Tavolari Simona
Published: February 2020

The link between asbestos exposure and the onset of thoracic malignancies is well established. However epidemiological studies have provided evidences that asbestos may be also involved in the development of gastrointestinal tumors, including intrahepatic cholangiocarcinoma (ICC). In line with this observation, asbestos fibers have been detected in the liver of patients with ICC. Although the exact mechanism still remains unknown, the presence of asbestos fibers in the liver could be explained in the light of their translocation pathway following ingestion/inhalation. In the liver, thin and long asbestos fibers could remain trapped in the smaller bile ducts, particularly in the stem cell niche of the canals of Hering, and exerting their carcinogenic effect for a long time, thus inducing hepatic stem/progenitor cells (HpSCs) malignant transformation. In this scenario, chronic liver damage induced by asbestos fibers over the years could be seen as a classic model of stem cell-derived carcinogenesis, where HpSC malignant transformation represents the first step of this process. This phenomenon could explain the recent epidemiological findings, where asbestos exposure seems mainly involved in ICC, rather than extrahepatic cholangiocarcinoma, development.
Association between Microsatellite Instability Status and Peri-Operative Release of Circulating Tumour Cells in Colorectal Cancer
Authors: Toh James W. T. , Lim Stephanie H. , MacKenzie Scott , de Souza Paul , Bokey Les , Chapuis Pierre , Spring Kevin J.
Published: February 2020

Microsatellite instability (MSI) in colorectal cancer (CRC) is a marker of immunogenicity and is associated with an increased abundance of tumour infiltrating lymphocytes (TILs). In this subgroup of colorectal cancer, it is unknown if these characteristics translate into a measurable difference in circulating tumour cell (CTC) release into peripheral circulation. This is the first study to compare MSI status with the prevalence of circulating CTCs in the peri-operative colorectal surgery setting. For this purpose, 20 patients who underwent CRC surgery with curative intent were enrolled in the study, and peripheral venous blood was collected at pre- (t1), intra- (t2), immediately post-operative (t3), and 14–16 h post-operative (t4) time points. Of these, one patient was excluded due to insufficient blood sample. CTCs were isolated from 19 patients using the IsofluxTM system, and the data were analysed using the STATA statistical package. CTC number was presented as the mean values, and comparisons were made using the Student t-test. There was a trend toward increased CTC presence in the MSI-high (H) CRC group, but this was not statistically significant. In addition, a Poisson regression was performed adjusting for stage (I-IV). This demonstrated no significant difference between the two MSI groups for pre-operative time point t1. However, time points t2, t3, and t4 were associated with increased CTC presence for MSI-H CRCs. In conclusion, there was a trend toward increased CTC release pre-, intra-, and post-operatively in MSI-H CRCs, but this was only statistically significant intra-operatively. When adjusting for stage, MSI-H was associated with an increase in CTC numbers intra-operatively and post-operatively, but not pre-operatively.
The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases
Authors: Kuҫi Zyrafete , Jordan Christiane , Wehner Sibylle , Sörensen Jan , Jarisch Andrea , Salzmann-Manrique Emilia , Pfeffermann Lisa-Marie , Klingebiel Thomas , Bader Peter , Kuҫi Selim
Published: February 2020

As the biology of mesenchymal stromal cells (MSCs) in patients with non-malignant hematological diseases (NMHD) is poorly understood, in the current study we performed a basic characterization of the phenotype and functional activity of NMHD-MSCs. Bone marrow (BM) of patients with thalassemia major (TM) possessed a significantly higher number of nucleated cells (BM-MNCs)/mL BM than healthy donors (P < 0.0001), which however did not result in a higher number of colony forming units-fibroblast (CFU-F) per milliliter BM. In contrast, from 1 × 106 BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (P < 0.013) and control group (P < 0.02). In addition, NMHD-MSCs expressed significantly lower levels of CD146 molecule, demonstrated an equal proliferation potential and differentiated along three lineages (osteoblasts, chondrocytes and adipocytes) as healthy donors’ MSCs, with exception of TM-MSCs which differentiated weakly in adipocytes. In contrast to other NMHD-MSCs and healthy donors’ MSCs, TM-MSCs demonstrated an impaired in vitro immunosuppressive potential, either. Noteworthy, the majority of the immunosuppressive effect of NMHD-MSCs was mediated through prostaglandin-E2 (PGE2), because indomethacin (an inhibitor of PGE2 synthesis) was able to significantly reverse this effect. Our results indicate therefore that NMHD-MSCs, except TM-MSCs, may be used as an autologous cell-based therapy for post-transplant complications such as graft failure, graft-versus-host disease (GvHD) and osteonecrosis.
NADPH Oxidases: The Vital Performers and Center Hubs during Plant Growth and Signaling
Authors: Hu Chun-Hong , Wang Peng-Qi , Zhang Peng-Peng , Nie Xiu-Min , Li Bin-Bin , Tai Li , Liu Wen-Ting , Li Wen-Qiang , Chen Kun-Ming
Published: February 2020

NADPH oxidases (NOXs), mostly known as respiratory burst oxidase homologs (RBOHs), are the key producers of reactive oxygen species (ROS) in plants. A lot of literature has addressed ROS signaling in plant development regulation and stress responses as well as on the enzyme’s structure, evolution, function, regulation and associated mechanisms, manifesting the role of NOXs/RBOHs as the vital performers and center hubs during plant growth and signaling. This review focuses on recent advances of NOXs/RBOHs on cell growth, hormone interaction, calcium signaling, abiotic stress responses, and immunity. Several primary particles, including Ca2+, CDPKs, BIK1, ROPs/RACs, CERK, FER, ANX, SnRK and SIK1-mediated regulatory mechanisms, are fully summarized to illustrate the signaling behavior of NOXs/RBOHs and their sophisticated and dexterous crosstalks. Diverse expression and activation regulation models endow NOXs/RBOHs powerful and versatile functions in plants to maintain innate immune homeostasis and development integrity. NOXs/RBOHs and their related regulatory items are the ideal targets for crop improvement in both yield and quality during agricultural practices.
Single-Cell RNA Sequencing in Human Retinal Degeneration Reveals Distinct Glial Cell Populations
Authors: Voigt Andrew P. , Binkley Elaine , Flamme-Wiese Miles J. , Zeng Shemin , DeLuca Adam P. , Scheetz Todd E. , Tucker Budd A. , Mullins Robert F. , Stone Edwin M.
Published: February 2020

Degenerative diseases affecting retinal photoreceptor cells have numerous etiologies and clinical presentations. We clinically and molecularly studied the retina of a 70-year-old patient with retinal degeneration attributed to autoimmune retinopathy. The patient was followed for 19 years for progressive peripheral visual field loss and pigmentary changes. Single-cell RNA sequencing was performed on foveal and peripheral retina from this patient and four control patients, and cell-specific gene expression differences were identified between healthy and degenerating retina. Distinct populations of glial cells, including astrocytes and Müller cells, were identified in the tissue from the retinal degeneration patient. The glial cell populations demonstrated an expression profile consistent with reactive gliosis. This report provides evidence that glial cells have a distinct transcriptome in the setting of human retinal degeneration and represents a complementary clinical and molecular investigation of a case of progressive retinal disease.
Astroglial Isopotentiality and Calcium-Associated Biomagnetic Field Effects on Cortical Neuronal Coupling
Authors: Martinez-Banaclocha Marcos
Published: February 2020

Synaptic neurotransmission is necessary but does not sufficiently explain superior cognitive faculties. Growing evidence has shown that neuron–astroglial chemical crosstalk plays a critical role in the processing of information, computation, and memory. In addition to chemical and electrical communication among neurons and between neurons and astrocytes, other nonsynaptic mechanisms called ephaptic interactions can contribute to the neuronal synchronization from different brain regions involved in the processing of information. New research on brain astrocytes has clearly shown that the membrane potential of these cells remains very stable among neighboring and distant astrocytes due to the marked bioelectric coupling between them through gap junctions. This finding raises the possibility that the neocortical astroglial network exerts a guiding template modulating the excitability and synchronization of trillions of neurons by astroglial Ca2+-associated bioelectromagnetic interactions. We propose that bioelectric and biomagnetic fields of the astroglial network equalize extracellular local field potentials (LFPs) and associated local magnetic field potentials (LMFPs) in the cortical layers of the brain areas involved in the processing of information, contributing to the adequate and coherent integration of external and internal signals. This article reviews the current knowledge of ephaptic interactions in the cerebral cortex and proposes that the isopotentiality of cortical astrocytes is a prerequisite for the maintenance of the bioelectromagnetic crosstalk between neurons and astrocytes in the neocortex.
PIK3R1W624R Is an Actionable Mutation in High Grade Serous Ovarian Carcinoma
Authors: D’Ambrosio Concetta , Erriquez Jessica , Arigoni Maddalena , Capellero Sonia , Mittica Gloria , Ghisoni Eleonora , Borella Fulvio , Katsaros Dionyssios , Privitera Silvana , Ribotta Marisa , Maldi Elena , Di Nardo Giovanna , Berrino Enrico , Venesio Tiziana , Ponzone Riccardo , Vaira Marco , Hall Douglas , Jimenez-Linan Mercedes , Paterson Anna L. , Calogero Raffaele A. , Brenton James D. , Valabrega Giorgio , Di Renzo Maria Flavia , Olivero Martina
Published: February 2020

Identifying cancer drivers and actionable mutations is critical for precision oncology. In epithelial ovarian cancer (EOC) the majority of mutations lack biological or clinical validation. We fully characterized 43 lines of Patient-Derived Xenografts (PDXs) and performed copy number analysis and whole exome sequencing of 12 lines derived from naïve, high grade EOCs. Pyrosequencing allowed quantifying mutations in the source tumours. Drug response was assayed on PDX Derived Tumour Cells (PDTCs) and in vivo on PDXs. We identified a PIK3R1W624R variant in PDXs from a high grade serous EOC. Allele frequencies of PIK3R1W624R in all the passaged PDXs and in samples of the source tumour suggested that it was truncal and thus possibly a driver mutation. After inconclusive results in silico analyses, PDTCs and PDXs allowed the showing actionability of PIK3R1W624R and addiction of PIK3R1W624R carrying cells to inhibitors of the PI3K/AKT/mTOR pathway. It is noteworthy that PIK3R1 encodes the p85α regulatory subunit of PI3K, that is very rarely mutated in EOC. The PIK3R1W624R mutation is located in the cSH2 domain of the p85α that has never been involved in oncogenesis. These data show that patient-derived models are irreplaceable in their role of unveiling unpredicted driver and actionable variants in advanced ovarian cancer.