bluuebunny/crossref_metadata_2025 huggingface dataset:
LEARNING SYSTEM DESIGN FOR GAME APPLICATIONS
Authors:   O. S. Popov Odessa National Academy of Telecommunications, Yegoshyna G.A. , Voronoy S.M. , Ovdieichuk A.A.
Published: May 2021

The presented paper investigates the problem of designing a learning system for agents in intelligent game applications based on Unity Game Engine and reinforcement machine learning algorithms. Modern trends in the game applications development are characterized by the active using of the concept of an intelligent agent as a behavior model of an active element in various situations with applying various strategies for interactions with other active elements and the environment. In recent years, there have been a significant number of advances in this area, such as DeepMind and the Deep Q learning architecture, the winning of the Go Game Champion with AlphaGo, OpenAI and PPO. Unity developers have implemented a support for machine learning and, in particular, for deep reinforcement learning in order to create a deep reinforcement learning the SDK (Software Development Kit) for game and simulation developers. With Unity and ML-Agents toolkits we can create physically, visually, and cognitively rich environments, including ones for evaluating new algorithms and strategies. However, learning system design for agents in Unity ML-Agents is possible only by using the Python API. The possibility of a learning system design for agents in the Flappy Bird game application based on the Unity Game Engine with using its own environment is discussed in this paper. Separately, the paper highlights typical features of the Flappy Bird gaming application environment. The environment can be implemented as a fully observable environment or a partially observable environment. The fully observable environment is suggested to be used due to all environment states in this case are seen in the playfield. Thus, the problem of strategy formation is considered as a Markov decision-making process and the agent directly observes the current state of the environment. Temporal Difference Learning is used as a learning method; it involves the assessment of a reward at each stage. Two separate environments, deterministic and stochastic, have been implemented, that allows to conduct further research and evaluation of strategy formation algorithms.
SPATIAL DIVERSITY SIGNAL TRANSMISSION IN DIGITAL TROPOSCATTER STATIONS
Authors:   О.S. Popov Odessa National Academy of Telecommunications, Pochernyaev V.N. , Syvkova N.M. ,   О.S. Popov Odessa National Academy of Telecommunications, Povkhlib V.S. ,   Kiev college of communication
Published: May 2021

The article examines the possibility of increasing the normalized throughput of digital troposcatter stations on the way of using space-separated signal transmission. Shown is a block diagram of the transmitting path of a digital troposcatter station with space-separated signal transmission. Methods of separation at the reception of signals acting at the input of the space-time coding device of the transmission path of the microwave digital troposcatter station are analyzed. Three methods of signal addition are considered in detail: linear addition; auto selection; optimal (quasi-optimal) addition. Various variants of addition are analyzed: before the demodulator and after the demodulator. The calculation of the normalized channel capacity as a function of the signal-to-noise ratio for the case of two transmitting antennas with known and unknown channel matrices is carried out. It was found that with two transmitting antennas and an unknown channel matrix, the normalized bandwidth does not differ from the case of using one transmitting antenna. The effect of cross-polarization isolation on the normalized channel capacity is analyzed, when one transmitting antenna emits signals of horizontal polarization, and the second transmitting antenna emits signals of vertical polarization. The values of the error probability are obtained for spatially-separated signal transmission to two transmitting antennas for two laws of distribution of a random variable - Rayleigh and Rice. The Rice distribution law of a random variable, the error probability is expressed through the modified zero-order Bessel function. The calculated data are shown in the table. The calculation was carried out in two frequency ranges allowed for the use of troposcatter communication facilities and for a channel without fading and for a channel with intersymbol interference.
Development and Validation of Tranexamic Acid Determination in Human Plasma by HPLC-MS/MS method
Authors: Aleshina A. V. , Komarov T. N. , Archakova O. A. , Shchelgacheva D. S. , Bagaeva N. S. , Davydanova V. V. , Savchenko A. Yu. , Shohin I. E.
Published: May 2021

Introduction. Tranexamic acid is one of the most common drugs used to stop bleeding after trauma, in surgery and gynecology. The most common analytical method for the determination of this compound is reversed-phase high-performance liquid chromatography (HPLC). However, this compound belongs to the group of so-called poorly retained compounds due to its chemical structure. It is necessary to develop an analytical method that will allow the determination of tranexamic acid in human blood plasma with the least time, resource costs and without the use of specialized columns.Aim. The aim of this study is to develop a method for tranexamic acid in human plasma by high performance liquid chromatography with tandem mass-spectrometry (HPLC-MS/MS) for pharmacokinetic studies.Materials and methods. Determination of tranexamic acid in plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation.Results and discussion. This method was validated by next parameters: selectivity, matrix effect, calibration curve, accuracy, precision, recovery, lower limit of quantification, carry-over effect and stability.Conclusion. The method of the determination of tranexamic acid in human plasma was developed and validated by HPLC-MS/MS. The linearity in plasma sample was achieved in the concentration range of 100.00–15000.00 ng/ml. Method could be applied to tranexamic acid determination in plasma for pharmacokinetics and bioequivalence studies.
Transfer of Impurities Determination Methods: Comparative Testing, Validation, Acceptance Criteria (Review)
Authors: Epshtein N. A.
Published: May 2021

Introduction. Different approaches are used for transfer of impurities determination methods. In most cases, comparative testing of samples or partial validation of methods is performed. At the same time, a number of issues important for practice are still relevant.Text. The features of methods validation and comparative testing of samples during the transfer of impurities determination methods are considered. Potential acceptance criteria – requirements to the permissible difference between results of transmitting and receiving laboratories – are given. The calculation formulas of the TOST test are considered, and the critical condition for the comparative testing of samples is given. The key points that should be taken into account when transferring the methods are discussed.Conclusion. The data and recommendations are presented, which are important for increasing the reliability of the transfer of the impurities determination methods.
Description of the System of State Registration of Medicines in the Republic of Georgia as a Development Potential of Domestic Manufacturers
Authors: Foteeva A. V. , Barshadskaya O. S. , Rostova N. B.
Published: May 2021

Introduction. One of the main business objectives of Russian pharmaceutical companies is export development. To obtain marketing authorization in countries with a good potential for business it is of greater importance to be competent in drugs registration procedure.Aim. The purpose of this study is to overview general aspects of registration procedure for generic drugs in Georgia for potential launching on pharmaceutical market.Materials and methods. For research purposes we have utilized data obtained from research articles, official websites, regulatory documents for drug registration procedure in both Russian Federation and Republic of Georgia, and documents of registration dossier. Also for this research we have applied benchmarking study, generalized and classified obtained information.Results and discussion. The similarities and differences of drug registration procedure have been determined, e.g. timelines, dossier format, and legal frameworks in both Russian Federation and Republic of Georgia. Also we have emphasized a list of features that could be benefiting for drug registration in Georgia.Conclusion. A review of the state regulation procedure in the field of drug circulation in the Republic of Georgia allows us to conclude that there are favorable conditions for state registration of drugs from a Russian manufacturer.
Targeted Synthesis and Analysis of Biologically Active Azomethine Derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
Authors: Chiriapkin A. S. , Kodonidi I. P. , Larsky M. V.
Published: May 2021

Introduction. Azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide are acyclic precursors of biologically active compounds derived from 5,6,7,8-tetrahydro-3H-benzoteopheno[2,3-d]pyrimidine-4-one. Examples of these groups of compounds with different pharmacological properties are given in the literature, but their cytostatic effect is mainly described. These data and the preparative availability allow us to judge the prospects for further study and molecular design in a number of azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide. Optimization of methods for the synthesis and analysis of substances of this series and the identification of structure-activity relationship are of considerable interest for medical chemistry and pharmaceutical science. The resulting leading compounds will allow us to further develop laboratory requirements for the synthesis of an active pharmaceutical substance.Aim. To make a predict, optimize the synthesis conditions and develop a method for high performance liquid chromatography (HPLC) analysis of pharmacologically active azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide.Materials and methods. The prediction of biological activity was carried out through the web resource PASS Online. The synthesis of the target azomethines was carried out by the interaction of aromatic aldehydes with 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide in an ethanol. The reaction was monitored by thin-layer chromatography (TLC). The determination of related impurities was done by HPLC. The analysis was carried out under the conditions of isocratic elution with a mobile phase of acetonitrile – water (70:30).Results and discussion. The results of the prediction of the biological activity of the constructed structures suggest the manifestation of cytostatic, antitubercular and anti-inflammatory activity characteristic of all target azomethines. The analysis of the reactivity revealed the influence of substituents of aldehydes contained in the aromatic core on the completeness of the condensation reaction. The spectral characteristics clearly confirmed the structure of the products, and the HPLC results showed the purity of the obtained substances, which is more than 95 %.Conclusion. As a result of the conducted studies, the structure of promising azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide was justified and the method of their synthesis and analysis by HPLC was optimized. In the future, the results of the research will allow us to identify the leading compounds with the specified pharmacological properties.
IMPLEMENTATION OF THE SCRUM MODEL IN THE DEVELOPMENT OF ONLINE SALES SYSTEMS OF MSMEs DURING THE COVID-19 PANDEMIC
Authors: Hidayat Wahyutama Fitri , Purnamawati Annida , Sarasati Fajar
Published: May 2021

A global pandemic or epidemic indicates a covid-19 infection that is very fast spreading throughout the world, including Indonesia. This has an impact on several sectors, one of which is the economic sector. There are various things that have caused the economic sector to be touched by the impact of the covid-19 virus, including government policies at both the central and regional levels that issued several regulations relating to restrictions on community mobility. Indirectly, things related to mobility restrictions or what is currently known as Pembatasan Sosial Berskala Besar (PSBB) have an impact on consumer behavior to switch to making purchases online. To address this, the online sales system is considered to be a solution for MSMEs to continue the buying and selling process. Using the Scrum model as a more efficient system development, feedback between users and developers who can work better to create a more interactive system. The results of this study are a website that can be used by UMKM as a means of selling their business products amid the Covid-19 pandemic.
Kebijakan Kenormalan Baru Destinasi Wisata di Kabupaten Kulon Progo
Authors: Fitri Lianawati  , Dyah Mutiarin  , Janianton Damanik
Published: May 2021

Pariwisata merupakan salah satu sektor yang paling terdampak wabah COVID-19 di Kabupaten Kulon Progo. Upaya pemulihan pariwisata dari COVID-19 harus komprehensif dan berkelanjutan. Artikel ini mendeskripsikan tentang kebijakan kenormalan baru pemerintah terhadap covid-19 pada destinasi pariwisata di Kabupaten Kulon Progo. Penelitian ini menggunakan analisis metode deskriptif kualitatif. Hasil penelitian mengungkapkan bahwa, sektor pariwisata selama pandemic dan masa kenormalan baru harus menerapkan (1) protokol kesehatan bagi destinasi wisata dengan memperhatikan kebersihan, kesehatan, keselamatan dan ketahanan lingkungan (CHSE) dengan menyediakan fasilitas cuci tangan, sabun, hand sanitizer, dan alat pengatur suhu. (2) menerapkan gerakan ‘sambanggo’ (3) pembatasan jumlah pengunjung untuk menghindari kerumunan dan pengaturan jarak (4) destinasi wisata dibuka secara bertahap
Strategi Daya Tarik Wisata Alam Curug Leuwi Bumi Dalam Implementasi Sistem Reservasi Digital
Authors: Irwan Tamrin  , Rusdin Tahir  , M. Liga Suryadana
Published: May 2021

Pengembangan pariwisata berbasis digital merupakan salah satu alternatif untuk menjawab permasalahan pariwisata massal yang kerap mengancam keberlangsungan destinasi pariwisata. Keberlanjutan dalam perspektif pariwisata tidak hanya tentang bagaimana lingkungan ekologis, tetapi juga bagaimana masyarakat setempat menjalani kehidupannya sehari-hari serta manfaatnya secara ekonomi. Penerapan teknologi reservasi digital merupakan salah satu terobosan yang diterapkan oleh daya tarik wisata alam Curug Leuwi Bumi di Provinsi Banten dalam upayanya mewujudkan pariwisata yang berkelanjutan. Penelitian ini bertujuan untuk menganalisis strategi pendampingan digitalisasi berupa teknologi sistem reservasi digital pada destinasi wisata, khususnya yang berbasis wisata alam. Metode kualitatif yang digunakan dalam penelitian ini dikembangkan dengan narasi deskriptif. Teknik pengumpulan data dilakukan dengan wawancara mendalam, observasi, dan studi pustaka. Hasil penelitian ini menunjukkan bahwa penerapan sistem reservasi digital dapat meningkatkan transparansi dan akuntabilitas pengelola daya tarik wisata Curug Leuwi Bumi.
KINERJA PELAYANAN TERPADU SATU PINTU DI DINAS PENANAMAN MODAL DAN PELAYANAN TERPADU SATU PINTU (DPMPTSP) KOTA PALEMBANG PROVINSI SUMATERA SELATAN
Authors: Pratiwi Rizki , Nurasa Heru , Anggraini Wike
Published: May 2021

Penelitian ini bertujuan untuk mengetahui kinerja pelayanan terpadu satu pintu di Dinas Penanaman Modal dan Pelayanan Terpadu Satu Pintu Kota Palembang Sumatera Selatan, dan mengidentifikasikan faktor-faktor penyebab menurunnya kinerja, serta mengetahui upaya- upaya apa yang dilakukan DPMPTSP Kota Palembang untuk kembali meningkatkan kinerja pegawai pada institusi tersebut. Metode penelitian yang digunakan dalam penelitian ini adalah  penelitian kualitatif dengan metode deskriptif dan pendekatan induktif. Teknik pengumpulan data adalah observasi, wawancara dan dokumentasi. Hasil penelitian menunjukkan bahwa kinerja Dinas Penanaman Modal dan Pelayanan Terpadu Satu Pintu Kota Palembang sudah baik. Meskipun terjadinya penurunan peringkat yang dikarenakan oleh beberapa faktor seperti keterbatasan anggaran, perubahan struktur pegawai, meningkatnya persaingan antar provinsi dan belum tersedianya mall pelayanan publik. Namun, DPMPTSP Kota Palembang dapat melakukan beberapa upaya untuk meningkatkan kinerjanya agar dapat meraih kembali predikat yang dicapai sebelumnya.
Körfez Ülkelerinde Kadınların Toplumsal Rollerindeki Değişim: Katar ve Birleşik Arap Emirlikleri Örnekleri Üzerinden Bir Karşılaştırma | Changing Roles of Arab Women in the Gulf Society: Comparison of Two Cases through Qatar and the United Arab Emirates
Authors: ÖZORAL Başak
Published: May 2021

Orta Doğu ülkeleri arasında Körfez İşbirliği Konseyi (KİK) ülkelerinin farklı bir konumu vardır, zira bu ülkeler son otuz yılda ekonomik, sosyal, politik ve kültürel yapılarında oldukça dramatik değişimler yaşamışlardır. KİK ülkelerinde kadınların toplum içindeki rolleri de bu değişimden payını almıştır. Bu çalışmanın amacı, KİK ülkelerinde yaşayan kadınların son otuz yıl içinde ekonomik, politik ve kültürel alanlardaki değişen rollerini incelemektir. Çalışmada Katar ve Birleşik Arap Emirlikleri (BAE) örnek ülkeler olarak ele alınarak karşılaştırma yapılmıştır. Körfezin küçük ülkesi Katar hem son derece tutucu yerel geleneklere sahip, hem de toplumsal değişimlerin en hızlı hissedildiği bölgelerden biridir, dolayısıyla kadınların yaşamında gözlenen değişikliklerin analizi için mükemmel bir örnektir. BAE ise Katar’a göre Batı kültürüne daha açık ve liberal yapısıyla kadınların değişen rollerinin incelenmesi için daha farklı bir ortam sunmaktadır. KİK ülkeleri içinde ekonomik gelişimin en hızlı olduğu ülkeler Katar ve BAE olduğundan bu iki ülkedeki değişimin kadınlar üzerindeki etkisinin daha çarpıcı olacağı düşünülmüş ve makale için örnek olarak ele alınmışlardır. Çalışmanın bulguları, kadınların Katar ve BAE’de yaşanan büyük dönüşümden nasıl etkilendiklerini göstermektedir. Makalede her iki ülkede kadınların son yıllarda sosyo-ekonomik yapıda ve politik alanda değişen rollerindeki benzerlikler ve farklılıklar belirtilmiştir. Ayrıca her iki ülkede kraliyet mensubu kadınların topluma rol model olmalarının etkileri de tartışılmıştır. Çalışmanın sonucuna göre bu iki Körfez ülkesinde kadınların toplumdaki etkisi ve katılımı artsa da hukuksal anlamda reformların yapılmaması kadınların yerellik ve modernleşme arasında kalmasına ve ciddi çelişkilerle yüzleşmelerine neden olmaktadır. Katar ve BAE ile ortak tarihsel, kültürel, ekonomik ve siyasi yapıyı paylaşan diğer KİK ülkelerindeki kadınların çok benzer durumlarla yüzleştiklerini söylemek mümkündür.
Feminist Edebiyat Eleştirisi Bağlamında Yeniden Yazım: Lavinia Örneği | Rewriting in the Context of Feminist Literary Criticism: The Case of Lavinia
Authors: ULU Aslıhan
Published: May 2021

Hikâye anlatmak, insanlık için bilgi ve deneyimlerini aktarmanın yanı sıra hayal kurma ve düşünme biçimini geliştirmesi bakımından da önemli bir yere sahiptir. Eski çağlara dayanan anlatı teknikleri ve kurguları günümüz edebiyatını ve dolayısıyla toplumlarını da etkisi altında tutmaya devam etmektedir. Bu araştırma, ataerkil ideolojinin tarih boyunca–özellikle Batı düşünce tarihi- destan ve mitlerde tekrar eden cinsel kimlikleri barındırdığını ve bu kimliklerin de günümüz toplumlarına sirayet ettiğini ileri sürer. Dolayısıyla bu çalışma, en eski anlatı biçimi olan, toplumlara ortak bir aidiyet ve kimlik veren destan ve mitlerin feminist edebiyat eleştirisi bağlamında yeniden yazımına odaklanır. Bu makalede, tarihsel olarak feminist edebiyat eleştirisinin gelişimi, mit eleştirisi ve sonucunda ortaya çıkan feminist mit yaratımı/yeniden yazımı düşünceleri irdelenmiştir. Tüm bu teorik yaklaşımlar çerçevesinde Ursula Le Guin’in Lavinia karakteri orijinal metin olan Vergilius’un Aeneis destanındaki aynı adlı karakteri ile karşılaştırmalı olarak incelenerek karakter analizi yapılmıştır.
Desislava Şenay Martinova'nın Alev Ateş Serisinde Madun Temsili | Desislava Şenay Martinova's Representation Of Subaltern In The Still Alev Ateş Series
Authors: GÜNAY YAVUZ Uğur
Published: May 2021

Sanatın her alanında toplumsal cinsiyet, sınıf, etnik ve dinsel kimlik üzerinden farklı kimliklerin yeniden üretildiği ve temsil edildiği görülmektedir. 2000 sonrası belgesel fotoğraf alanında yer alan temsillerden biri hem dünyada hem de Türkiye’de madunun temsilidir. Bu çalışma madunların gündelik yaşamlarına bu bağlamda toplumsal sıkıntılarına ve ötekileştirilmelerine odaklanmaktadır. Çalışmaya tekil bir örneklem olarak Desislava Şenay Martinova’nın fotoğrafları seçilmiş, daha özelde Martinova’nın Alev Ateş adlı serisi makale içerisinde analiz edilmiştir. Bir öteki olarak madun kavramını Spivak’ın çalışmalarını merkeze alarak okuyacak çalışma, sırtını öteki kavramına yaslamakta iken aynı zamanda belgesel fotoğrafta fotoğrafçının, fotoğrafını çekeceği kişi/lere yaklaşımını ve toplumsal belgeci fotoğraf anlayışı ile günümüzde fotoğrafçının ele aldığı sorunlara dair bir değişim veya sorunların giderilmesi yolunda etkisini de tartışmaya açmaktadır. Sonuç olarak bu çalışmada madunun ötekiliğinin toplumsal cinsiyet üzerinden iki kat olarak arttırıldığı, kadın olmanın bedelinin egemenlerin kurduğu iktidar ilişkisi noktasında daha ağır olduğu saptanmıştır. Ayrıca fotoğrafçının temsil sırasındaki konumunun da önemi ortaya çıkarılmıştır.
Antimicrobial Activity of Human Fetal Membranes: From Biological Function to Clinical Use
Authors: Ramuta Taja Železnik , Šket Tina , Starčič Erjavec Marjanca , Kreft Mateja Erdani
Published: May 2021

The fetal membranes provide a supportive environment for the growing embryo and later fetus. Due to their versatile properties, the use of fetal membranes in tissue engineering and regenerative medicine is increasing in recent years. Moreover, as microbial infections present a crucial complication in various treatments, their antimicrobial properties are gaining more attention. The antimicrobial peptides (AMPs) are secreted by cells from various perinatal derivatives, including human amnio-chorionic membrane (hACM), human amniotic membrane (hAM), and human chorionic membrane (hCM). By exhibiting antibacterial, antifungal, antiviral, and antiprotozoal activities and immunomodulatory activities, they contribute to ensuring a healthy pregnancy and preventing complications. Several research groups investigated the antimicrobial properties of hACM, hAM, and hCM and their derivatives. These studies advanced basic knowledge of antimicrobial properties of perinatal derivatives and also provided an important insight into the potential of utilizing their antimicrobial properties in a clinical setting. After surveying the studies presenting assays on antimicrobial activity of hACM, hAM, and hCM, we identified several considerations to be taken into account when planning future studies and eventual translation of fetal membranes and their derivatives as antimicrobial agents from bench to bedside. Namely, (1) the standardization of hACM, hAM, and hCM preparation to guarantee rigorous antimicrobial activity, (2) standardization of the antimicrobial susceptibility testing methods to enable comparison of results between various studies, (3) investigation of the antimicrobial properties of fetal membranes and their derivatives in the in vivo setting, and (4) designation of donor criteria that enable the optimal donor selection. By taking these considerations into account, future studies will provide crucial information that will enable reaching the optimal treatment outcomes using the fetal membranes and their derivatives as antimicrobial agents.
Cross-Talk Between Inflammation and Fibroblast Growth Factor 10 During Organogenesis and Pathogenesis: Lessons Learnt From the Lung and Other Organs
Authors: Marega Manuela , Chen Chengshui , Bellusci Saverio
Published: May 2021

The adult human lung is constantly exposed to irritants like particulate matter, toxic chemical compounds, and biological agents (bacteria and viruses) present in the external environment. During breathing, these irritants travel through the bronchi and bronchioles to reach the deeper lung containing the alveoli, which constitute the minimal functional respiratory units. The local biological responses in the alveoli that follow introduction of irritants need to be tightly controlled in order to prevent a massive inflammatory response leading to loss of respiratory function. Cells, cytokines, chemokines and growth factors intervene collectively to re-establish tissue homeostasis, fight the aggression and replace the apoptotic/necrotic cells with healthy cells through proliferation and/or differentiation. Among the important growth factors at play during inflammation, members of the fibroblast growth factor (Fgf) family regulate the repair process. Fgf10 is known to be a key factor for organ morphogenesis and disease. Inflammation is influenced by Fgf10 but can also impact Fgf10 expression per se. Unfortunately, the connection between Fgf10 and inflammation in organogenesis and disease remains unclear. The aim of this review is to highlight the reported players between Fgf10 and inflammation with a focus on the lung and to propose new avenues of research.
PNMA5 Promotes Bone Metastasis of Non-small-Cell Lung Cancer as a Target of BMP2 Signaling
Authors: Huang Fei , Cao Yaqiang , Wang Caihong , Lan Ruilong , Wu Bing , Xie Xianhe , Hong Jinsheng , Fu Lengxi , Wu Gui
Published: May 2021

Bone metastases frequently occur in NSCLC patients at the late stage, indicating poor survival. However, mechanisms about the initiation of NSCLC bone metastases remain largely unclear. In our previous reports, BMP2 signaling activation has been found to enhance NSCLC bone metastases through enhancing carcinoma cells migration, invasion, osteoclasts differentiation and osteoblasts immature differentiation. Nevertheless, downstream target genes of BMP2 contributing to those processes still remain unknown. In this project, we find that the expression of Pnma5 is higher in metastatic bone tumors of Lewis lung carcinoma than in metastatic lung tumors and parental Lewis lung cells. Pnma5 overexpression not only can promote cell migration and invasion of NSCLC cells but also tumor-induced osteoclasts differentiation. Interestingly, knockdown of Pnma5 in Lewis lung cells blocks BMP2 signaling from inducing Lewis lung cells migration and invasion. Although BMP2 signaling can promote Lewis lung cells-induced osteoclasts differentiation from macrophages, this effect can also be blocked when Pnma5 is knocked down in Lewis lung cells. Moreover, Pnma5 can promote NSCLC bone metastases in vivo as the downstream target of BMP2. Those results above indicate that BMP2 signaling enhances NSCLC bone metastases via its direct downstream target gene Pnma5. This research reveals the detailed molecular mechanism about how BMP2 signaling contributes to NSCLC bone metastases via PNMA5 and provides a new potential therapeutic target for the treatment of NSCLC bone metastases.
Smart Actuators Based on External Stimulus Response
Authors: Zheng Qinchao , Xu Chenxue , Jiang Zhenlin , Zhu Min , Chen Chen , Fu Fanfan
Published: May 2021

Smart actuators refer to integrated devices that are composed of smart and artificial materials, and can provide actuation and dampening capabilities in response to single/multi external stimuli (such as light, heat, magnetism, electricity, humidity, and chemical reactions). Due to their capability of dynamically sensing and interaction with complex surroundings, smart actuators have attracted increasing attention in different application fields, such as artificial muscles, smart textiles, smart sensors, and soft robots. Among these intelligent material, functional hydrogels with fiber structure are of great value in the manufacture of smart actuators. In this review, we summarized the recent advances in stimuli-responsive actuators based on functional materials. We emphasized the important role of functional nano-material-based additives in the preparation of the stimulus response materials, then analyzed the driving response medium, the preparation method, and the performance of different stimuli responses in detail. In addition, some challenges and future prospects of smart actuators are reported.
A Methylene Blue Assisted Electrochemical Sensor for Determination of Drug Resistance of Escherichia coli
Authors: Duan Rongshuai , Fang Xiao , Wang Dongliang
Published: May 2021

Due to the abuse of antibiotics in clinical, animal husbandry, and aquaculture, drug-resistant pathogens are produced, which poses a great threat to human and the public health. At present, a rapid and effective drug sensitivity test method is urgently needed to effectively control the spread of drug-resistant bacteria. Using methylene blue as a redox probe, the electrochemical signals of methylene blue in drug-resistant Escherichia coli strains were analyzed by a CV method. Graphene ink has been used for enhancing the electrochemical signal. Compared with the results of the traditional drug sensitivity test, we proposed a rapid electrochemical drug sensitivity test method which can effectively identify the drug sensitivity of Escherichia coli. The sensitivity of four E. coli isolates to ciprofloxacin, gentamicin, and ampicillin was tested by an electrochemical drug sensitivity test. The respiratory activity value %RA was used as an indicator of bacterial resistance by electrochemical method.
Association Between Triglyceride-Glucose Index and Hypertension: A Meta-Analysis
Authors: Wang Yi , Yang Wei , Jiang Xiao
Published: May 2021

Background: Triglyceride-glucose (TyG) index is a recently proposed surrogate indicator of insulin resistance. Previous studies evaluating the association between TyG index and hypertension risk in general adult population showed inconsistent results. We performed a meta-analysis to systematically evaluate this association.

Methods: Observational studies, which evaluated the independent association between TyG index and hypertension in the general adult population, were identified by systematic search of PubMed, Embase, Web of Science, Wanfang data, and Chinese National Knowledge Infrastructure databases. A random-effect model, which incorporated the potential intra-study heterogeneity, was used for the meta-analysis.

Results: Eight observational studies including 200,044 participants were included. Results showed that compared with those with the lowest category of TyG index, subjects with the highest category of TyG index were associated with higher odds of hypertension [adjusted risk ratio (RR): 1.53, 95% confidence interval (CI): 1.26–1.85, I2 = 54%, P < 0.001]. Sensitivity analysis by excluding one dataset at a time showed consistent result (adjusted RR: 1.44–1.62, P all < 0.001). Results of univariate meta-regression analysis showed that differences in sample size, mean age, male proportion, mean body mass index, and study quality score among the included studies did not have significant influence on the association between TyG index and hypertension (P values all > 0.10), suggesting that differences in these characteristics may not be the major source of heterogeneity. Subgroup analyses showed that study characteristics such as study design, participant ethnicity, age, or sex of the participants did not significantly affect the association (P for subgroup difference all >0.05).

Conclusions: Higher TyG index may be associated with higher odds of hypertension in general adult population. Large-scale prospective cohort studies are needed to validate these findings, and further studies are needed to elucidate the potential pathophysiological mechanisms underlying the association between TyG index and hypertension.
Identification of Potential miRNA-mRNA Regulatory Network Contributing to Hypertrophic Cardiomyopathy (HCM)
Authors: Wang Lin , Lu Fengmin , Xu Jing
Published: May 2021

Background: Hypertrophic cardiomyopathy (HCM) is a myocardial disease with unidentified pathogenesis. Increasing evidence indicated the potential role of microRNA (miRNA)-mRNA regulatory network in disease development. This study aimed to explore the miRNA-mRNA axis in HCM.

Methods: The miRNA and mRNA expression profiles obtained from the Gene Expression Omnibus (GEO) database were used to identify differentially expressed miRNAs (DEMs) and genes (DEGs) between HCM and normal samples. Target genes of DEMs were determined by miRTarBase. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify biological functions of the DEGs and DEMs. miRNA-mRNA regulatory network was constructed to identify the hub genes and miRNAs. Logistic regression model for HCM prediction was established basing on the network.

Results: A total of 224 upregulated and 366 downregulated DEGs and 10 upregulated and 14 downregulated DEMs were determined. We identified 384 DEM-targeted genes, and 20 of them were overlapped with the DEGs. The enriched functions include extracellular structure organization, organ growth, and phagosome and melanoma pathways. The four miRNAs and three mRNAs, including hsa-miR-373, hsa-miR-371-3p, hsa-miR-34b, hsa-miR-452, ARHGDIA, SEC61A1, and MYC, were identified through miRNA-mRNA regulatory network to construct the logistic regression model. The area under curve (AUC) values over 0.9 suggested the good performance of the model.

Conclusion: The potential miRNA-mRNA regulatory network and established logistic regression model in our study may provide promising diagnostic methods for HCM.
miR-29a/b1 Regulates the Luteinizing Hormone Secretion and Affects Mouse Ovulation
Authors: Guo Yang , Wu Youbing , Shi Jiahao , Zhuang Hua , Ci Lei , Huang Qin , Wan Zhipeng , Yang Hua , Zhang Mengjie , Tan Yutong , Sun Ruilin , Xu Leon , Wang Zhugang , Shen Ruling , Fei Jian
Published: May 2021

miR-29a/b1 was reportedly involved in the regulation of the reproductive function in female mice, but the underlying molecular mechanisms are not clear. In this study, female mice lacking miR-29a/b1 showed a delay in vaginal opening, irregular estrous cycles, ovulation disorder and subfertility. The level of luteinizing hormone (LH) was significantly lower in plasma but higher in pituitary of mutant mice. However, egg development was normal in mutant mice and the ovulation disorder could be rescued by the superovulation treatment. These results suggested that the LH secretion was impaired in mutant mice. Further studies showed that deficiency of miR-29a/b1 in mice resulted in an abnormal expression of a number of proteins involved in vesicular transport and exocytosis in the pituitary, indicating the mutant mice had insufficient LH secretion. However, the detailed mechanism needs more research.
Human Adaptation to Coastal Hazards in Greater Bridgetown, Barbados
Authors: Mycoo Michelle , Robinson Stacy-Ann , Nguyen Cindy , Nisbet Catherine , Tonkel Rock
Published: May 2021

As urban risks associated with a changing climate continue to intensify, it is increasingly important to broaden our understanding of climate vulnerabilities in coastal cities and human adaptation to climate-related hazards. Coastal cities in small island developing states in the Caribbean stand to be among the most climate-impacted. This paper explores vulnerability to coastal hazards (sea-level rise, storm surges and flooding) in Barbados’ capital city and its urban corridor—Greater Bridgetown. Specifically, it is a qualitative survey of climate change vulnerabilities and human adaptation in the study domain that is underpinned by three research questions: 1) In what ways is Greater Bridgetown vulnerable to coastal hazards? 2) What are the human dimensions of this vulnerability? and 3) What are the associated human adaptations? We apply a four-component adaptive urban governance framework to explore the role of the city’s historical development, urban morphology, national-level institutions and relevant government and other stakeholder initiatives in shaping, reducing and/or increasing vulnerability to coastal hazards. The paper relates primarily to the governance dimension of the risk reduction framework articulated by the Intergovernmental Panel on Climate Change. In totality, a case is presented that highlights Greater Bridgetown’s capacity for coastal/urban resilience, but which cannot be maximized without institutional prioritization of vulnerability, increased stakeholder “buy-in” and participation, along with significant investment in adaptation and the protection of valuable coastal infrastructure. The findings are of relevance to human adaptation within coastal cities of small island developing states.
Cross-Species Application of Illumina iScan Microarrays for Cost-Effective, High-Throughput SNP Discovery
Authors: Fountain Emily D. , Zhou Li-Chen , Karklus Alyssa , Liu Qun-Xiu , Meyers James , Fontanilla Ian K. C. , Rafael Emmanuel Francisco , Yu Jian-Yi , Zhang Qiong , Zhu Xiang-Lei , Pei En-Le , Yuan Yao-Hua , Banes Graham L.
Published: May 2021

Microarrays can be a cost-effective alternative to high-throughput sequencing for discovering novel single-nucleotide polymorphisms (SNPs). Illumina’s iScan platform dominates the market, but their commercial microarray products are designed for model organisms. Further, the platform outputs data in a proprietary format. This cannot be easily converted to human-readable genotypes or be merged with pre-existing data. To address this, we present and validate a novel pipeline to facilitate data analysis from cross-species application of Illumina microarrays. This facilitates the generation of a compatible VCF from iScan data and the merging of this with a second VCF comprising genotypes derived from other samples and sources. Our pipeline includes a custom script, iScanVCFMerge (presented as a Python package), which we validate using iScan data from three great ape genera. We conclude that cross-species application of microarrays can be a rapid, cost-effective approach for SNP discovery in non-model organisms. Our pipeline surmounts the common challenges of integrating iScan genotypes with pre-existing data.
Case Report: Identification of Novel Variants in ERCC4 and DDB2 Genes in Two Tunisian Patients With Atypical Xeroderma Pigmentosum Phenotype
Authors: Nabouli Imen , Chikhaoui Asma , Othman Houcemeddine , Elouej Sahar , Jones Meriem , Lagarde Arnaud , Rekaya Meriem Ben , Messaoud Olfa , Zghal Mohamed , Delague Valerie , Levy Nicolas , De Sandre-Giovannoli Annachiara , Abdelhak Sonia , Yacoub-Youssef Houda
Published: May 2021

Xeroderma Pigmentosum (XP) is a rare genetic disorder affecting the nucleotide excision repair system (NER). It is characterized by an extreme sensitivity to sunlight that induces cutaneous disorders such as severe sunburn, freckling and cancers. In Tunisia, six complementation groups have been already identified. However, the genetic etiology remains unknown for several patients. In this study, we investigated clinical characteristics and genetic defects in two families with atypical phenotypes originating from the central region in Tunisia. Clinical investigation revealed mild cutaneous features in two patients who develop multiple skin cancers at later ages, with no neurological disorders. Targeted gene sequencing revealed that they carried novel variants. A homozygous variation in the ERCC4 gene c.1762G>T, p.V588F, detected in patient XP21. As for patient XP134, he carried two homozygous mutations in the DDB2 gene c.613T>C, p.C205R and c.618C>A, p.S206R. Structural modeling of the protein predicted the identified ERCC4 variant to mildly affect protein stability without affecting its functional domains. As for the case of DDB2 double mutant, the second variation seems to cause a mild effect on the protein structure unlike the first variation which does not seem to have an effect on it. This study contributes to further characterize the mutation spectrum of XP in Tunisian families. Targeted gene sequencing accelerated the identification of rare unexpected genetic defects for diagnostic testing and genetic counseling.
Novel Insights Into Genetic Responses for Waterlogging Stress in Two Local Wheat Cultivars in Yangtze River Basin
Authors: Wei Mingmei , Li Xiu , Yang Rui , Li Liulong , Wang Zhuangzhi , Wang Xiaoyan , Sha Aihua
Published: May 2021

Wheat (Triticum aestivum L.), the most widely cultivated crop, is affected by waterlogging that limited the wheat production. Given the incompleteness of its genome annotation, PacBio SMRT plus Illumina short-read sequencing strategy provided an efficient approach to investigate the genetic regulation of waterlogging stress in wheat. A total of 947,505 full-length non-chimetric (FLNC) sequences were obtained with two wheat cultivars (XM55 and YM158) with PacBio sequencing. Of these, 5,309 long-non-coding RNAs, 1,574 fusion genes and 739 transcription factors were identified with the FLNC sequences. These full-length transcripts were derived from 49,368 genes, including 47.28% of the genes annotated in IWGSC RefSeq v1.0 and 40.86% genes encoded two or more isoforms, while 27.31% genes in the genome annotation of IWGSC RefSeq v1.0 were multiple-exon genes encoding two or more isoforms. Meanwhile, the individuals with waterlogging treatments (WL) and control group (CK) were selected for Illumina sequencing. Totally, 6,829 differentially expressed genes (DEGs) were detected from four pairwise comparisons. Notably, 942 DEGs were overlapped in the two comparisons (i.e., XM55-WL vs. YM158-WL and YM158-WL vs. YM158-CK). Undoubtedly, the genes involved in photosynthesis were downregulated after waterlogging treatment in two cultivars. Notably, the genes related to steroid biosynthesis, steroid hormone biosynthesis, and downstream plant hormone signal transduction were significantly upregulated after the waterlogging treatment, and the YM158 variety revealed different genetic regulation patterns compared with XM55. The findings provided valuable insights into unveiling regulation mechanisms of waterlogging stress in wheat at anthesis and contributed to molecular selective breeding of new wheat cultivars in future.
Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering
Authors: Ghorbani Atefeh , Quinlan Emma M. , Larijani Mani
Published: May 2021

The immune system is unique among all biological sub-systems in its usage of DNA-editing enzymes to introduce targeted gene mutations and double-strand DNA breaks to diversify antigen receptor genes and combat viral infections. These processes, initiated by specific DNA-editing enzymes, often result in mistargeted induction of genome lesions that initiate and drive cancers. Like other molecules involved in human health and disease, the DNA-editing enzymes of the immune system have been intensively studied in humans and mice, with little attention paid (< 1% of published studies) to the same enzymes in evolutionarily distant species. Here, we present a systematic review of the literature on the characterization of one such DNA-editing enzyme, activation-induced cytidine deaminase (AID), from an evolutionary comparative perspective. The central thesis of this review is that although the evolutionary comparative approach represents a minuscule fraction of published works on this and other DNA-editing enzymes, this approach has made significant impacts across the fields of structural biology, immunology, and cancer research. Using AID as an example, we highlight the value of the evolutionary comparative approach in discoveries already made, and in the context of emerging directions in immunology and protein engineering. We introduce the concept of 5-dimensional (5D) description of protein structures, a more nuanced view of a structure that is made possible by evolutionary comparative studies. In this higher dimensional view of a protein’s structure, the classical 3-dimensional (3D) structure is integrated in the context of real-time conformations and evolutionary time shifts (4thdimension) and the relevance of these dynamics to its biological function (5thdimension).
Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence
Authors: Moreira-Filho José T. , Silva Arthur C. , Dantas Rafael F. , Gomes Barbara F. , Souza Neto Lauro R. , Brandao-Neto Jose , Owens Raymond J. , Furnham Nicholas , Neves Bruno J. , Silva-Junior Floriano P. , Andrade Carolina H.
Published: May 2021

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor.
Rab10-Positive Tubular Structures Represent a Novel Endocytic Pathway That Diverges From Canonical Macropinocytosis in RAW264 Macrophages
Authors: Kawai Katsuhisa , Nishigaki Arata , Moriya Seiji , Egami Youhei , Araki Nobukazu
Published: May 2021

Using the optogenetic photo-manipulation of photoactivatable (PA)-Rac1, remarkable cell surface ruffling and the formation of a macropinocytic cup (premacropinosome) could be induced in the region of RAW264 macrophages irradiated with blue light due to the activation of PA-Rac1. However, the completion of macropinosome formation did not occur until Rac1 was deactivated by the removal of the light stimulus. Following PA-Rac1 deactivation, some premacropinosomes closed into intracellular macropinosomes, whereas many others transformed into long Rab10-positive tubules without forming typical macropinosomes. These Rab10-positive tubules moved centripetally towards the perinuclear Golgi region along microtubules. Surprisingly, these Rab10-positive tubules did not contain any endosome/lysosome compartment markers, such as Rab5, Rab7, or LAMP1, suggesting that the Rab10-positive tubules were not part of the degradation pathway for lysosomes. These Rab10-positive tubules were distinct from recycling endosomal compartments, which are labeled with Rab4, Rab11, or SNX1. These findings suggested that these Rab10-positive tubules may be a part of non-degradative endocytic pathway that has never been known. The formation of Rab10-positive tubules from premacropinosomes was also observed in control and phorbol myristate acetate (PMA)-stimulated macrophages, although their frequencies were low. Interestingly, the formation of Rab10-positive premacropinosomes and tubules was not inhibited by phosphoinositide 3-kinase (PI3K) inhibitors, while the classical macropinosome formation requires PI3K activity. Thus, this study provides evidence to support the existence of Rab10-positive tubules as a novel endocytic pathway that diverges from canonical macropinocytosis.