bluuebunny/crossref_metadata_2025 huggingface dataset:
ОСОБЛИВОСТІ ВИКОРИСТАННЯ РРО У СИСТЕМІ ФІНАНСОВОГО ОБЛІКУ
Authors: Фатенок-Ткачук Алла , Пех Юлія
Published: December 2021

Стаття присвячена актуальним питанням визначення важливості використання реєстратора розрахункових операцій суб’єктами малого бізнесу. У роботі обґрунтовано необхідність застосування реєстратора розрахункових операцій (РРО) як ефективного методу контролю доходів господарюючих суб’єктів та процесу справляння податків, обмеження обсягів «тіньового» руху готівкових коштів, захисту прав споживачів. Проаналізовано та систематизовано фактори впливу держави на можливість встановлення пристрою, переваги та недоліки його застосування вітчизняними підприємствами. Досліджено та узагальнено нормативно-правову базу щодо застосування платниками єдиного податку реєстраторів розрахункових операцій у системі фінансового обліку. Окреслено резерви підвищення рівня економічного розвитку України, використовуючи реєстратор розрахункових операцій (РРО). Наведено шляхи підвищення актуальності питання реформування та вдосконалення системи оподаткування діяльності фізичних осіб-підприємців в Україні.
ДОСЛІДЖЕННЯ ЕКОНОМІЧНИХ ВІДНОСИН УКРАЇНИ З ФРАНЦІЄЮ
Authors: Рахман Махбубур , Морєва Маргарита
Published: December 2021

Метою статті є пошук методів вирішення проблем співробітництва між Україною та Францією, розробка проекту з розвитку економічних відносин цих країн та розробка рекомендацій щодо вдосконалення зовнішньої економічної діяльності України. У статті визначено стан, тенденції та основні цілі зовнішньоекономічної політики у сучасних умовах. Виявлено позицію Франції та інструменти двосторонньої співпраці в економічній сфері. Проведено структурний аналіз балансу імпорту та експорту з Францією та динамічний аналіз за обсягами торгівлі товарами і послугами з ЄС, визначено прогрес сфери торговельно-економічного співробітництва. Проведено динамічний аналіз загального товарообігу між Україною та Францією та зовнішньоторговельного сальдо, визначено фактори, які впливають на позитивну та негативну динаміку у зовнішній торгівлі Виявлено головні проблеми зовнішньоекономічної діяльності України та можливі шляхи їх усунення.
Review of phosphocholine substituents on bacterial pathogen glycans: Synthesis, structures and interactions with host proteins
Authors: Wakarchuk Warren W. , Young N. Martin , J. Foote Simon
Published: December 2021

Among the non-carbohydrate components of glycans, the addition of phosphocholine (ChoP) to the glycans of pathogens occurs more rarely than acetylation or methylation, but it has far more potent biological consequences. These arise from ChoP's multiple interactions with host proteins, which are important at all stages of the infection process. These stages include initial adherence to cells, encountering the host's innate immune system and then the adaptive immune system. Thus, in the initial stages of an infection, ChoP groups are an asset to the pathogen, but they can turn into a disadvantage subsequently. In this review, we have focussed on structural aspects of these phenomena. We describe the biosynthesis of the ChoP modification, the structures of the pathogen glycans known to carry ChoP groups and the host proteins that recognize ChoP.
Urban Policy And Heritage Planning: The Disproportionate Designation Of Heritage Conservation Districts (HCDs) In The City Of Toronto
Authors: Barnwell Chante
Published: December 2021

This Major Research Paper (MRP) examines the disproportionate designation of Heritage Conservation Districts (HCDs) within the City of Toronto, which are predominantly located in the City's downtown core, compared to the City's inner suburban areas. To illustrate the discrepancies in HCD designation, two potential HCDs in Scarborough, one of three inner suburbs in Toronto, are chronologically examined. Both Agincourt and Midland Park’s HCD represent the most recent examples of heritage designation in the inner suburb, which stands as the only area in the City that has zero HCDs. Before the case studies are discussed, the effects of Toronto's 1998 amalgamation, select timeframes of the City's planning history and recent changes to Provincial planning legislation that govern municipalities' heritage approach are examined. It is determined that a series of factors contribute to the disproportionate designation of HCDs in the City of Toronto. These factors include the incremental designation of heritage properties post amalgamation, the lengthy heritage designation process, the intergovernmental nature of municipal heritage policies, the lack of public education on the benefits of heritage and a complex HCD prioritization process all contribute to the disproportionate designation of HCD’s in the City of Toronto. Four key recommendations are offered to help resolve the heritage designation issue in the City of Toronto.

Keywords: Heritage Conservation Districts; Toronto; Urban Planning, Urban Policy, Heritage Urbanism.
Towards a Bilingual Binational Translation Method: The Amputated Tongue Collection of Short Stories as a Sample
Authors: Burbara Rawiya
Published: December 2021

Translators and writers are divided into two main groups regarding the method of translation that should be adopted in translating texts. One group believes that the translator should be true to the translated text, while the other group believes that the translator has the right to recreate the text into a more beautiful one.  This study deals with this issue from these two points of view and tries to answer the following questions: Why do we translate? What should we translate? How do we translate? The study relies on an innovative translation method developed by the Board of Maktoub Project for Translation that belongs to Van Leer Institute in Jerusalem to answer these questions. A group of about one hundred Arab and Jewish translators translated Arabic literature texts into Hebrew in an internationally new method, which is neither individual nor collective. It is a bilingual binational method. The translators consist of pairs of a Jewish or/and Arab translator, an Arab/or Jewish literary editor, and a linguistic editor, believing that translation is a text and culture, heritage, and traditions of a people or nation. This dual method gave the translated text its right of accuracy after it had been translated by one translator who can make mistakes due to his ignorance of the writer's culture. The study's conclusion confirms that bilingual binational translation is more fruitful and more accurate because it is based on dialogue, bilingual, and binational cultural knowledge.
SOCIAL NETWORKING WEBSITES: NEW EDUCATIONAL SPACE
Authors: Lamanauskas Vincentas
Published: December 2021

Over the latter decade the spread of information communication technologies was going on in various directions. Technological possibilities grew up very significantly (Lamanauskas, 2011). Especially rapid was the development of the internet and technologies related with it. A lot of internet service providers occurred in the market, their number still continues to grow. The internet link methods change - from the ordinary usage of phone line modems (dial - up) to broadband internet technology (DSL) and cable TV internet nets. It can be asserted, that over the mentioned period Web 1.0 internet (static, used for getting information) was changed by Web 2.0 internet (social). The internet diaries, social portals, technologies allowing live communication on the internet (Internet Relay Chat, IRC), talk programme Windows Live Messenger (MSN), ICQ forums and other have occurred and are spreading. With the occurrence of “Skype”, internet telephony acquired a qualitatively new characteristic and practically became a daily routine. Thus, today a consumer can create his profile on the internet, can make friends, communicate in the interest groups and so on. It can be stated, that every human being in his own way contributes to the internet and at the same time to ICT development, in general. It is obvious, that together with technological problems arise social internet problems as well. Social networking websites (SNW) are closely related with economical, psychological, educational, valeological and other aspects. There is a lack of researches based on socio-educational social networking website aspects. It is important to know not only how much time the consumers spend surfing the net, but how much time is allotted for communicating in social networking websites, which of them are the most popular and why, how the respondents evaluate social networking website functions, what in general they know about them, what advantages, disadvantages and threats they discern. Finally, it is important to find out whether usage of social networking websites makes information – communication abilities better in any way.
UNIVERSITY STUDENTS’ INFORMATION SOURCES OF EDUCATION FOR SUSTAINABLE DEVELOPMENT ISSUES AND THEIR PERCEPTIONS OF ENVIRONMENTAL PROBLEMS
Authors: Kukkonen Jari , Kärkkäinen Sirpa , Keinonen Tuula
Published: December 2021

Mass media consumption has expanded from traditional mass media – television broadcasting, newspapers, radio - into new media, such as the Internet. Information about environmental issues such as global warming, water and air pollution and other environmental problems, comes mainly from the media. In Finland nowadays the Internet is generally the most important source of news for young people. The media has also been used in a variety of ways relating to education for sustainable development. In the survey, education for sustainable development, students’ opinions were asked on 73 items concerning different dimensions of education for sustainable development. This study focuses on two of these items: how university students from different disciplines get information about education for sustainable development issues and which environmental problems they perceive as being the most important. It was found that although students get information about education for sustainable development issues mainly from television and newspapers almost an equal amount comes from the Internet, and lectures are the fourth source of information. Students perceived climate change and the lack of clean water as being the most important environmental problems, the second was the decrease in biodiversity and the least important, malaria. Those students whose information source was mainly television did not perceive biodiversity as being that important environmental problem.
Keywords: education for sustainable development, environmental problems, environmental information sources.
De cuerpo presente: diálogos sobre la pandemia entre el teatro y la educación
Authors: Suasnábar Juan Manuel , Ferreyro Rocio
Published: December 2021

La pandemia del COVID-19 generó a escala planetaria una irrupción del devenir cotidiano, modificando radicalmente las maneras de estar y de relacionarnos con el mundo. Cuerpos reconfigurados en pos de una continuidad con distintas perspectivas, expectativas y horizontes, claman en el tránsito del año 2020 por volver a su esencia. Desde este punto de partida, exploramos y reflexionamos, bajo la mirada del teatro, acerca de la relación entre cuerpo, presencia y virtualidad, con la hipótesis de que las conceptualizaciones del mundo teatral pueden extenderse para pensar el acontecer en el mundo escolar. Finalmente se reseñan, a modo de ejemplo, algunas experiencias que buscaron, en el marco de las medidas de cuidado, situar el cuerpo presente.
Fecha de recepción: 8/4/2021Fecha de aceptación: 28/7/2021
Circadian Biorhythmicity in Normal Pressure Hydrocephalus - A Case Series Report
Authors: Herbowski Leszek
Published: December 2021

Continuous monitoring of intracranial pressure is a well established medical procedure. Still, little is known about long-term behavior of intracranial pressure in normal pressure hydrocephalus. The present study is designed to evaluate periodicity of intracranial pressure over long-time scales using intraventricular pressure monitoring in patients with normal pressure hydrocephalus. In addition, the circadian and diurnal patterns of blood pressure and body temperature in those patients are studied. Four patients, selected with “probable” normal pressure hydrocephalus, were monitored for several dozen hours. Intracranial pressure, blood pressure, and body temperature were recorded hourly. Autocorrelation functions were calculated and cross-correlation analysis were carried out to study all the time-series data. Autocorrelation results show that intracranial pressure, blood pressure, and body temperature values follow bimodal (positive and negative) curves over a day. The cross-correlation functions demonstrate causal relationships between intracranial pressure, blood pressure, and body temperature. The results show that long-term fluctuations in intracranial pressure exhibit cyclical patterns with periods of about 24 hours. Continuous intracranial pressure recording in “probable” normal pressure hydrocephalus patients reveals circadian fluctuations not related to the day and night cycle. These fluctuations are causally related to changes in blood pressure and body temperature. The present study reveals the complete loss of the diurnal blood pressure and body temperature rhythmicities in patients with “probable” normal pressure hydrocephalus.
Renan Konferansı ve Nâmık Kemal’in Müdâfaanâme’sinin Oryantalist İddialar Bağlamında Değerlendirilmesi
Authors: KABAKCI Yusuf
Published: December 2021

Ernest Renan’ın 29 Mart 1883’te Sorbon Üniversitesinde “İslam ve Bilim” başlığıyla verdiği konferans hakkında birçok reddiye ve eleştirel yayınlar yapılmıştır. Renan’a reddiye yazanlardan birisi de Osmanlı aydınlarından Nâmık Kemal’dir. Konferanstan üç ay sonra risalesine başlamış ve dört ayda çalışmasını tamamlamıştır. Midilli Adasında kısıtlı imkânlarla ama büyük bir hevesle başladığı çalışmasını sipariş ettiği kitapları elde edemediğinden istediği seviyeye getiremediği için yayımlamamıştır. Renan Müdâfaanâmesi adı verilen makale ilk defa yazarının vefatından yirmi yıl sonra yayımlanabilmiş sonra başka baskıları da yapılmıştır. Çoğunlukla Renan’ın iddiaları üzerinden giderek İslam’ın bilime engel olmadığını ve Renan gibi oryantalistlerin İslam ve Müslümanlar hakkında yeterli bilgiye sahip olmadıklarını söylemiştir. Renan’ın İslam-felsefe ilişkisi, Arap ırkı ve Müslümanların cahil ve bağnaz oldukları gibi iddialarına İslam Tarihi’nden ve Hıristiyanlıktan mukayeseli örneklerle cevaplar vermiştir. Müdâfaanâme, kısıtlı imkânlarla yazılması ve tarafların uzmanlık alanlarının farklı olması gibi sebeplerle Renan’a tam bir cevap olamasa da özelikle Türkiye’de ilgi görmüştür. Türk edebiyat ve siyaset tarihinde müstesna bir yeri olan yazarın bu konudaki niyet ve gayreti Osmanlı aydınlarının duruşunu göstermesi ve sonraki nesiller için örneklik teşkil etmesi bakımından takdire şayandır.
İslam Hukukunda Cezalandırmada Gözetilmesi Gereken Esaslar
Authors: ATEŞ Üveys
Published: December 2021

Bir toplumun huzur ve güvenliğinin temin edilmesi ve toplum fertlerinin hukukunun korunması, o toplumda adil bir cezalandırma sisteminin bulunmasına bağlıdır. Bunun için cezalandırma sisteminin bir takım ilke ve esaslara sahip olması elzemdir. Adaletin hâkim kılınmasının temel amaç olarak görüldüğü İslam hukukunda da, cezalandırma sisteminin bu amacı gerçekleştirmeye dönük esasları bulunmaktadır. Gerek naslarda ve Hz. Peygamber’in (s.a.v.) uygulamalarında gerekse İslam hukukçularının ictihadlarında bu esasların izleri görülmektedir. Öte yandan suçluyu cezalandırma safhası, işlediği tespit edilen suça karşılık gelecek cezanın takdir edilmesi ve bu cezanın infaz edilmesi aşamalarını kapsamaktadır. Bu çalışmada İslam ceza hukukuna göre her iki aşamada gözetilmesi gereken ilke ve esaslar, ilgili naslardan, fıkıh kaynaklarından ve konuyla alakalı çağdaş dönemde yapılan akademik çalışmalardan istifade edilerek tespit edilmeye çalışılmıştır. Bu bağlamda tespit edilen; masum insanların cezalandırılmasının önüne geçmek için ceza vermede ihtiyatlı hareket edilmesi, adaletin gereği yerine getirilirken kimseye ayrıcalık tanınmaması, cezaların suçu önleyici mahiyette olmakla birlikte işlenen suç ile orantılı olması, suçlunun haysiyetinin ve temel haklarının ihlal edilmemesi prensiplerinin, adaletin sağlanması açısından öneminin ve gerekliliğinin ortaya konması amaçlanmıştır.
Application of spectral analysis for determine the phase shift of signals with equal amplitudes using full-wave transformation when measuring the characteristics of weapons
Authors: Tyshko S. , Lavrut O. , Smolar V. , Zabula O. , Chernichenko Yu.
Published: December 2021

The article defines the list of technical characteristics of armaments and military equipment (ARM), the value of which is measured using phase methods. An analysis of known methods that have found wide application in measuring technology, which is designed to determine the technical characteristics associated with the measurement of phase shift during the development, manufacture and operation of weapons. Based on this analysis, it was determined that the measuring systems are designed to determine the phase shift of two harmonic signals in their composition have two channels of information transmission. This architecture of the implementation of measuring systems leads to the fact that a significant impact on the accuracy of the proposed measurement problem, makes a component of the error due to the phase symmetry of the signal transmission channels, as well as internal and external noise. As an alternative approach to solving the measurement problem of determining the phase shift of two harmonic signals, which will significantly reduce the error component due to phase asymmetry of information transmission channels, it is proposed to use the signal obtained by summing harmonic signals after full-wave transformation followed by spectral analysis. In order to implement the above approach, a measurement problem was set to determine the phase shift of two harmonic signals, using spectral analysis of the signal obtained by summing the harmonic signals after their full-wave transformation. A list of assumptions required for the synthesis of analytical relations that establish the relationship between the spectra of phases and amplitudes (power) of the signal obtained by summing harmonic signals after their full-wave transformation and phase shift of two harmonic signals. Analytical relationships are proposed that establish the relationship between the above characteristics. It is shown that the values of the spectrum of phases and amplitudes, which are calculated using the proposed expressions, differ from the values obtained in the calculations using the Fourier series coefficients, not more than 0.1%.
Dynamic fusion of images from the visible and infrared channels of sightseeing system by complex matrix formalism
Authors: Khaustov D. , Khaustov Ya. , Ryzhov Ye. , Burashnikov O. , Lychkovskyy E. , Nastishin Yu.
Published: December 2021

The employment of new mathematical and computer approaches for the fusion of target images from the visible and infrared channels of the sightseeing system (SSS) is one of the ways to increase the efficiency of the SSS of armored vehicles. Modern approaches to improving the efficiency of image fusion are aimed to increase the visibility of the target via improving the quality indices of fused images. This paper proposes a fundamentally new approach to image fusion, namely dynamic image fusion, at which the target is observed in the mode of a video clip composed of a sequence of stationary fused images obtained at different parameters of fusion, in contrast to traditional stationary image fusion, at which the decision is made from one fused image. Unlike stationary image fusion, aimed to increase the visibility of the target, the dynamic image fusion allows one to enhance the conspicuity of the target. The principle of dynamic image fusion proposed in this paper is based on matrix formalism, in which the fused image is constructed in the form of a complex vector function, which by its mathematical form is analogous to the Jones vector of elliptically polarized light wave, which in turn opens the possibility of matrix transformation of the complex vector of the fused image and consequently its parameterization by analogy with the Jones matrix formalism for the light wave. The article presents mathematical principles of matrix formalism, which is the basis for dynamic image fusion, gives examples of stationary and dynamic image fusion by the method of complex vector function and compares with the corresponding images, fused by algorithms of weight addition in the field of real and complex scalars. It is shown that by selecting weight coefficients, the general form of a complex amplitude vector image can be reduced to the algorithms of weight and averaged addition in the field of real scalars, weight amplitude and RMS-image in the field of complex scalar numbers, and geometric-mean image in the field of complex vectors, which, thereby, are partial cases of the general form of the complex amplitude image in the field of complex vectors.

The animated images obtained by the method of complex vector function illustrate the increase of conspicuity of the object of observation due to the dynamic change of the fusion parameters.
Analysis of Ocular Biometric Parameters in Patients with Cystoid Macular Edema
Authors: Gorbunova N. Yu. , Voskresenskaya A. A. , Yakovlev R. A. , Pozdeeva N. A.
Published: December 2021

Relevance. Cataract surgeries are among the most frequently performed ophthalmic surgeries in the world. Despite the fact that they become less traumatic every year, such interventions are still accompanied by post-surgery complications, one of which is cystic macular edema (CME) or Irwin–Gass syndrome. Purpose. To analyze ocular biometric parameters in patients with CME. Material and Methods. The study included 40 patients (40 eyes) with post-surgery CME. All patients underwent ultrasound biometry, axial length measurement, crystalline lens thickness measurement with Bio&Pachy Meter AL-4000 (Tomey, Japan) and optical coherence tomography (OCT) with Cirrus HD-OCT 5000 (Carl Zeiss, Germany) to assess central foveal thickness. Depending on the axial length, all eyes were divided into “long” and “short” relative to the average axial length of 23.3 mm. The data was analyzed with STATISTICA 10 software (StatSoft Inc., USA). Results. The incidence of CME after uncomplicated cataract surgery in Cheboksary branch of the S. Fyodorov Eye Microsurgery Federal State Institution amounted to 0.002%. Axial length among patients with CME ranged from 20.53 mm to 25.4 mm; the average value amounted to 22.67 ± 1.05 mm. The majority of eyes were “short” – 31 eyes (77.5%), whereas 9 eyes (22.5%) were “long”. “Short” eyes exhibited a greater crystalline lens thickness (4.81 ± 0.53 mm) compared to “long” eyes (4.42 ± 0.42 mm) (рM-U = 0.014). Conclusion. The development of CME after uncomplicated cataract surgery is more often observed in eyes with axial length smaller than 23.3 mm.
Adenocarcinoma de vulva: un reporte de caso tipo glándula mamaria
Authors: Alarcon Andrade Carlos , Rivadeneira Santana Nery , Montes Lainez Hector Daniel
Published: December 2021

Introducción: Los tumores malignos de vulva son tumores raros del tracto genital femenino, que representan menos del 1 % de los tumores malignos del sexo femenino, cerca del 95% de estos son carcinoma escamo celulares, los adenocarcinomas son el tipo histológico menos frecuente, con 36 casos reportados hasta el año 2020.
Caso Clínico: Presentamos el caso de una mujer de 36 años con antecedente de histerectomía total por miomatosis, con cuadro clínico de 1 año de evolución caracterizado por una masa indolora en labio mayor izquierdo la cual se somete a biopsia que reporta adenocarcinoma motivo por el cual se somete a vulvectomia radical, en resultado patológico definitivo se confirma el diagnostico de adenocarcinoma de vulva tipo glándula mamaria.
Evolución: Se realiza vulvectomía radical + vaciamiento ganglionar inguino-iliaco bilateral. El estudio histo-patológico definitivo reveló adenocarcinoma de vulva tipo glándula mamaria pobremente diferenciado G3, Unifocal, con metástasis en 22/25 ganglios derechos y 30/30 izquierdos. Un estudio reportó recidiva local extensa, metástasis ganglionares pélvicas, retroperitoneales, mediastinales, axilares, cervicales y pulmonar. Se inició Paclitaxel 137 mg semanal. Se  completa quimioterapia hasta 11ra semana posterior a lo cual presentó infección de lecho tumoral y fallece.
Conclusión: En el presente caso el curso clínico de adenocarcinoma de vulva tipo glándula mamaria fue agresivo con una supervivencia inferior a 5 meses.
Scheduling and Sequencing Musical Events in Pure Data with Scheme for Pd
Authors: Duncan Iain
Published: December 2021

Scheme for Pd is a newly released open-source external for Pure Data, enabling scripting Pd with s7 Scheme Lisp. In this experience report, the author introduces Scheme for Pd and demonstrates its use for scheduling and sequencing musical events in s7 Scheme.
A Supramolecular Nanoparticle of Pemetrexed Improves the Anti-Tumor Effect by Inhibiting Mitochondrial Energy Metabolism
Authors: Liu Hui , Guo Chunlei , Shang Yuhong , Zeng Lin , Jia Haixue , Wang Zhongyan
Published: December 2021

In recent years, supramolecular nanoparticles consisting of peptides and drugs have been regarded as useful drug delivery systems for tumor therapy. Pemetrexed (PEM) is a multitarget drug that is effective for many cancers, such as non-small cell lung cancer. Here, RGD-conjugated molecular nanoparticles mainly composed of an anticancer drug of PEM (PEM-FFRGD) were prepared to deliver PEM to tumors. The peptide could self-assemble into a nanoparticle structure with diameter of about 20 nm. Moreover, the nanoparticle showed favorable solubility and biocompatibility compared with those of PEM, and the MTT test on A549 and LLC cells showed that the PEM-FFRGD nanoparticles had stronger cytotoxic activity than PEM alone. Most importantly, the nanoparticle could promote tumor apoptosis and decrease mitochondrial energy metabolism in tumors. In vivo studies indicated that PEM-FFRGD nanoparticles had enhanced antitumor efficacy in LLC tumor-bearing mice compared to that of PEM. Our observations suggested that PEM-FFRGD nanoparticles have great practical potential for application in lung cancer therapy.
CHNQD-00603 Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by the miR-452-3p-Mediated Autophagy Pathway
Authors: Xin Shanshan , Li Shao-Ming , Gao Ling , Zheng Jing-Jing , Wu Yan-Wei , Shao Chang-Lun , Ren Wen-Hao , Zhi Keqian
Published: December 2021

Background: Periodontitis is a chronic and progressive disease accompanied by bone loss. It is still a challenge to restore the bone structure. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a decisive role in bone restoration and regeneration. Marine natural products (MNPs) have multiple biological activities, including anti-tumor and anti-inflammatory properties. However, the exploration of MNPs in osteogenesis is far from sufficient.

Methods: We obtained a series of derivatives through structural optimization from 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloid isolated from Scopulariopsis sp. Some preliminary cytological experiments showed that CHNQD-00603, obtained by adding a methoxy group to the position C3 and a hydroxyl group to the position C4 of 4-phenyl-3,4-dihydroquinolin-2(1H)-one, might promote the osteogenic differentiation of BMSCs. To further investigate the effects of CHNQD-00603 on BMSCs, we performed a CCK-8 assay and qRT-PCR, alkaline phosphatase staining (ALP), and alizarin red S staining to assess the cytotoxicity and the ability of osteogenic differentiation of CHNQD-00603. The autophagy level was assessed and validated by WB, qRT-PCR, and transmission electron microscopy. Then, 3-methyladenine (3-MA) was added to further examine the role of autophagy. Based on the expression of autophagy-related genes, we predicted and examined the potential miRNAs by bioinformatics.

Results: CCK-8 assay showed that CHNQD-00603 at 1 µg/ml did not influence BMSCs activity. However, the proliferation rate decreased from the seventh day. qRT-PCR, ALP staining, ALP activity assay, and Alizarin red S staining showed that the best concentration of CHNQD-00603 to promote osteogenic differentiation was 1 µg/ml. Further investigations indicated that CHNQD-00603 activated autophagy, and the inhibition of autophagy by 3-MA attenuated CHNQD-00603-enhanced osteogenic differentiation. Subsequently, the findings from bioinformatics and qRT-PCR indicated that miR-452-3p might be a regulator of autophagy and osteogenesis. Furthermore, we transfected BMSCs with miR-452-3p NC and mimics separately to further determine the function of miR-452-3p. The data showed that the overexpression of miR-452-3p moderated the level of autophagy and osteogenic differentiation of CHNQD-00603-treated BMSCs.

Conclusion: Our data suggested that CHNQD-00603 promoted the osteogenic differentiation of BMSCs by enhancing autophagy. Meanwhile, miR-452-3p played a regulatory role in this process.
Towards Higher Sensitivity of Mass Spectrometry: A Perspective From the Mass Analyzers
Authors: Li Chang , Chu Shiying , Tan Siyuan , Yin Xinchi , Jiang You , Dai Xinhua , Gong Xiaoyun , Fang Xiang , Tian Di
Published: December 2021

Mass spectrometry (MS) is one of the most widely used analytical techniques in many fields. Recent developments in chemical and biological researches have drawn much attention to the measurement of substances with low abundances in samples. Continuous efforts have been made consequently to further improve the sensitivity of MS. Modifications on the mass analyzers of mass spectrometers offer a direct, universal and practical way to obtain higher sensitivity. This review provides a comprehensive overview of the latest developments in mass analyzers for the improvement of mass spectrometers’ sensitivity, including quadrupole, ion trap, time-of-flight (TOF) and Fourier transform ion cyclotron (FT-ICR), as well as different combinations of these mass analyzers. The advantages and limitations of different mass analyzers and their combinations are compared and discussed. This review provides guidance to the selection of suitable mass spectrometers in chemical and biological analytical applications. It is also beneficial to the development of novel mass spectrometers.
The Challenge of Non-Stationary Feedbacks in Modeling the Response of Debris-Covered Glaciers to Climate Forcing
Authors: Nicholson Lindsey , Wirbel Anna , Mayer Christoph , Lambrecht Astrid
Published: December 2021

Ongoing changes in mountain glaciers affect local water resources, hazard potential and global sea level. An increasing proportion of remaining mountain glaciers are affected by the presence of a surface cover of rock debris, and the response of these debris-covered glaciers to climate forcing is different to that of glaciers without a debris cover. Here we take a back-to-basics look at the fundamental terms that control the processes of debris evolution at the glacier surface, to illustrate how the trajectory of debris cover development is partially decoupled from prevailing climate conditions, and that the development of a debris cover over time should prevent the glacier from achieving steady state. We discuss the approaches and limitations of how this has been treated in existing modeling efforts and propose that “surrogate world” numerical representations of debris-covered glaciers would facilitate the development of well-validated parameterizations of surface debris cover that can be used in regional and global glacier models. Finally, we highlight some key research targets that would need to be addressed in order to enable a full representation of debris-covered glacier system response to climate forcing.
Large-Scale Triaxial Tests on Dilatancy Characteristics of Lean Cemented Sand and Gravel
Authors: Yu Hang , Shen Xue-mei , Ye Yu-chen , Yang Jie , Zhu Chen-hui
Published: December 2021

The dilatancy equation, which describes the plastic strain increment ratio and its dependence on the stress state, is an important component of the elastoplastic constitutive model of geotechnical materials. In order to reveal their differences of the dilatancy value determined by the total volume strain increment ratio and the real value of lean cemented sand and gravel (LCSG) materials, in this study, a series of triaxial compression tests, equiaxial loading and unloading tests, and triaxial loading and unloading tests are conducted under different cement contents and confining pressures. The results reveal that hysteretic loops appear in the stress–strain curves of equiaxial loading and unloading tests, and triaxial loading and unloading tests and that the elastic strain is an important component of the total strain. The hysteretic loop size increases with an increase in the stress level or consolidation stress, whereas the shape remains unchanged. Furthermore, with an increase in the cement content, the dilatancy value determined by the total volume strain increment ratio becomes smaller than that determined by the plastic strain increment ratio, and the influence of the elastic deformation cannot be ignored. Thus, in practical engineering scenarios, especially in the calculation of LCSG dam structures, the dilatancy equation of LCSG materials should be expressed by the plastic strain increment ratio, rather than the total volume strain increment rati.
Opinions of Future Teachers on Training in Social Sciences Didactics
Authors: Felices-De la Fuente María del Mar , Chaparro-Sainz Álvaro
Published: December 2021

At present, an understanding of the teaching practices at university and the opinion of students about these practices is limited, at least in certain knowledge areas. Given this diagnosis and in the context of Social Sciences Didactics, we consider it important to analyze teaching practices and how they impact future teachers. Consequently, concerned about the quality of training offered to students, this study aims to know their opinion about which teaching practices they consider most appropriate to train in Social Sciences Didactics, once they finish the subjects related to this area. To this end, a non-experimental quantitative design has been used, involving collecting information through a questionnaire completed by 875 students from seven Spanish universities studying for the Degree in Primary Education. The data was analyzed from a triple perspective, an analysis of the descriptive statistics of the items contemplated in this research, the existing correlations between them, and a statistical analysis based on the gender variable. The results show that the treatment of controversial issues and the didactic outings outside the university classroom are the strategies most valued by the students in teaching specific content of the subject Social Sciences Didactics. The results also show significant differences in the responses to each item depending on the gender variable. We conclude that students widely value university teaching practices related to implementing active methodologies, analyzing current social and environmental issues, and collaborative work dynamics. Likewise, it is observed that women have, on the whole, a better opinion than men regarding these types of methodologies and strategies.
The Association Between Dietary Inflammatory Index and Sex Hormones Among Postmenopausal Women in the US
Authors: Chen Wen-Yu , Fu Yan-Peng , Zhong Wen , Zhou Min
Published: December 2021

Aims

Diet has been found to have an important effect on sex hormones. The effect of diet-induced inflammation on sex hormones has not been studied in detail among women. Therefore, we aimed to investigate the association between energy-adjusted dietary inflammatory index (E-DII) and sex hormones among postmenopausal women.

Methods

This study used data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 waves. A total of 1183 postmenopausal women who provided information on two 24-hour dietary intake recalls, sex hormones including total testosterone (TT), estradiol (E2), TT/E2, sex hormone-binding globulin (SHBG), free estradiol (FE2) and free testosterone (FT), as well as selected covariates were included. Linear regression and restricted cubic spline evaluated the association between E-DII and sex hormones. Effect modification by body mass index (BMI) and type of menopause was then examined in stratified analysis.

Results

After adjusting for covariates, linear regression showed that E-DII was positively associated with TT (P=0.035), FT (P=0.026) and TT/E2 (P=0.065). TT (P-nonlinear = 0.037) and TT/E2 (P-nonlinear = 0.035) had significant nonlinear association with E-DII. E2 (P-nonlinear = 0.046) and FE2 (P-nonlinear = 0.027) depicted a nonlinear U-shaped significant association with E-DII, the two inflection points were found at the E-DII score of -0.22 and 0.07, respectively, the associations in natural menopausal women were more pronounced.

Conclusions

Our study indicates that several indicators of androgen and estrogen were associated with E-DII in postmenopausal women. Further research is needed to understand the underlying mechanisms.
Screening and Functional Analysis of TPO Gene Mutations in a Cohort of Chinese Patients With Congenital Hypothyroidism
Authors: Wang Huijjuan , Wang Wenxia , Chen Xi , Shi Hailong , Shi Yinmin , Ding Guifeng
Published: December 2021

Backgrounds

As a crucial enzyme in thyroid hormone synthesis, the genetic defective thyroid peroxidase (TPO) was one of the main genetic factors leading to congenital hypothyroidism (CH).

Methods

Mutations in the TPO gene were screened and identified in 219 patients with CH from northwest China by using high-throughput sequencing and bioinformatics analysis. The biological function of detected variants was studied by in vitro experiments and homology modeling.

Results

Nineteen rare variants, including seven novel ones, were detected in 17 of 219 patients (7.8%). Most cases were detected with one single heterozygous variant, and only two patients were detected with multiple variants, i.e., compounds for (1) IVS7-1G>A, p.Ala443Val, and p.Arg769Trp and (2) p.Asn592Ser and p.Asn798Lys. The biological function of the four missense mutations (i.e., p.Ala443Val, p.Arg769Trp, p.Asn592Ser, and p.Asn798Lys) they carried were further studied. Experimental data showed that these four mutations did not affect the protein expression level of the TPO gene but remarkably reduced the peroxidase activity toward guaiacol oxidation, retaining 8–32% of activity of the wild-type protein. The comparison of the predicted 3-D structures of wild-type and mutant TPO proteins showed that these four amino acid substitutions changed the non-covalent interactions of studied residues that might alter the structure and function of the TPO protein.

Conclusion

This study was the first to analyze the TPO mutation spectrum of patients with CH in northwest China. Our data indicated that the TPO mutation was not a common reason to cause CH in China. The functional data may help to clarify the structure-function relationship of the TPO protein and provide further evidence for the elucidation of the genetic etiology of CH.
Tracking Cloud Forests With Cloud Technology and Random Forests
Authors: Pascual Pasky , Pascual Cam
Published: December 2021

Hotspots of endemic biodiversity, tropical cloud forests teem with ecosystem services such as drinking water, food, building materials, and carbon sequestration. Unfortunately, already threatened by climate change, the cloud forests in our study area are being further endangered during the Covid pandemic. These forests in northern Ecuador are being razed by city dwellers building country homes to escape the Covid virus, as well as by illegal miners desperate for money. Between August 2019 and July 2021, our study area of 52 square kilometers lost 1.17% of its tree cover. We base this estimate on simulations from the predictive model we built using Artificial Intelligence, satellite images, and cloud technology. When simulating tree cover, this model achieved an accuracy between 96 and 100 percent. To train the model, we developed a visual and interactive application to rapidly annotate satellite image pixels with land use and land cover classes. We codified our algorithms in an R package—loRax—that researchers, environmental organizations, and governmental agencies can readily deploy to monitor forest loss all over the world.
Measuring What Matters—A Holistic Approach to Measuring Well-Being in Endometriosis
Authors: McPherson Lori , Bhattacharya Siladitya
Published: December 2021

Endometriosis is a common condition which affects women in a number of ways and impairs their ability to live a full and meaningful life. Evaluative research has traditionally taken its cue from a medical approach which has forced women to choose one area of functioning as their primary concern, and tended to use a narrow definition of treatment success which ignores general well-being. While recent trials have included quality of life (QOL) measures as outcomes, these have not been able to capture the totality of the impact of the disease and its treatment on a woman's capability to do what she might want to do and be who she might want to be. A capability approach might overcome this barrier, but the available tools will need to be refined and validated in women with endometriosis before this can be integrated within everyday clinical and research practice.
Prognostic Value of Neoantigen Load in Immune Checkpoint Inhibitor Therapy for Cancer
Authors: Zou Xue-lin , Li Xiao-bo , Ke Hua , Zhang Guang-yan , Tang Qing , Yuan Jiao , Zhou Chen-jiao , Zhang Ji-liang , Zhang Rui , Chen Wei-yong
Published: December 2021

Immune checkpoint inhibitors (ICIs) have made great progress in the field of tumors and have become a promising direction of tumor treatment. With advancements in genomics and bioinformatics technology, it is possible to individually analyze the neoantigens produced by somatic mutations of each patient. Neoantigen load (NAL), a promising biomarker for predicting the efficacy of ICIs, has been extensively studied. This article reviews the research progress on NAL as a biomarker for predicting the anti-tumor effects of ICI. First, we provide a definition of NAL, and summarize the detection methods, and their relationship with tumor mutation burden. In addition, we describe the common genomic sources of NAL. Finally, we review the predictive value of NAL as a tumor prediction marker based on various clinical studies. This review focuses on the predictive ability of NAL’s ICI efficacy against tumors. In melanoma, lung cancer, and gynecological tumors, NAL can be considered a predictor of treatment efficacy. In contrast, the use of NAL for urinary system and liver tumors requires further research. When NAL alone is insufficient to predict efficacy, its combination with other indicators can improve prediction efficiency. Evaluating the response of predictive biomarkers before the treatment initiation is essential for guiding the clinical treatment of cancer. The predictive power of NAL has great potential; however, it needs to be based on more accurate sequencing platforms and technologies.
The Importance of Ecological Accommodation Space and Sediment Supply for Cold-Water Coral Mound Formation, a Case Study From the Western Mediterranean Sea
Authors: Wang Haozhuang , Titschack Jürgen , Wienberg Claudia , Korpanty Chelsea , Hebbeln Dierk
Published: December 2021

The formation of cold-water coral (CWC) mounds is commonly seen as being the result of the sustained growth of framework-forming CWCs and the concurrent supply and deposition of terrigenous sediments under energetic hydrodynamic conditions. Yet only a limited number of studies investigated the complex interplay of the various hydrodynamic, sedimentological and biological processes involved in mound formation, which, however, focused on the environmental conditions promoting coral growth. Therefore, we are still lacking an in-depth understanding of the processes allowing the on-mound deposition of hemipelagic sediments, which contribute to two thirds of coral mound deposits. To investigate these processes over geological time and to evaluate their contribution to coral mound formation, we reconstructed changes in sediment transport and deposition by comparing sedimentological parameters (grain-size distribution, sediment composition, accumulation rates) of two sediment cores collected from a Mediterranean coral mound and the adjacent seafloor (off-mound). Our results showed that under a turbulent hydrodynamic regime promoting coral growth during the Early Holocene, the deposition of fine siliciclastic sediments shifted from the open seafloor to the coral mounds. This led to a high average mound aggradation rate of >130 cm kyr–1, while sedimentation rates in the adjacent off-mound area at the same time did not exceed 10 cm kyr–1. Thereby, the baffling of suspended sediments by the coral framework and their deposition within the ecological accommodation space provided by the corals seem to be key processes for mound formation. Although, it is commonly accepted that these processes play important roles in various sedimentary environments, our study provided for the first time, core-based empirical data proving the efficiency of these processes in coral mound environment. In addition, our approach to compare the grain-size distribution of the siliciclastic sediments deposited concurrently on a coral mound and on the adjacent seafloor allowed us to investigate the integrated influence of coral mound morphology and coral framework on the mound formation process. Based on these results, this study provides the first conceptual model for coral mound formation by applying sequence stratigraphic concepts, which highlights the interplay of the coral-framework baffling capacity, coral-derived ecological accommodation space and sediment supply.
Hydroxylation of N-acetylneuraminic Acid Influences the in vivo Tropism of N-linked Sialic Acid-Binding Adeno-Associated Viruses AAV1, AAV5, and AAV6
Authors: Lopez-Gordo Estrella , Orlowski Alejandro , Wang Arthur , Weinberg Alan , Sahoo Susmita , Weber Thomas
Published: December 2021

Adeno-associated virus (AAV) vectors are promising candidates for gene therapy. However, a number of recent preclinical large animal studies failed to translate into the clinic. This illustrates the formidable challenge of choosing the animal models that promise the best chance of a successful translation into the clinic. Several of the most common AAV serotypes use sialic acid (SIA) as their primary receptor. However, in contrast to most mammals, humans lack the enzyme CMAH, which hydroxylates cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac) into cytidine monophosphate-N-glycolylneuraminic acid (CMP-Neu5Gc). As a result, human glycans only contain Neu5Ac and not Neu5Gc. Here, we investigate the tropism of AAV1, 5, 6 and 9 in wild-type C57BL/6J (WT) and CMAH knock-out (CMAH−/−) mice. All N-linked SIA-binding serotypes (AAV1, 5 and 6) showed significantly lower transduction of the heart in CMAH−/− when compared to WT mice (5–5.8-fold) and, strikingly, skeletal muscle transduction by AAV5 was almost 30-fold higher in CMAH−/− compared to WT mice. Importantly, the AAV tropism or distribution of expression among different organs was also affected. For AAV1, AAV5 and AAV6, expression in the heart compared to the liver was 4.6–8-fold higher in WT than in CMAH−/− mice, and for AAV5 the expression in the heart compared to the skeletal muscle was 57.3-fold higher in WT than in CMAH−/− mice. These data thus strongly suggest that the relative abundance of Neu5Ac and Neu5Gc plays a role in AAV tropism, and that results obtained in commonly used animal models might not translate into the clinic.