bluuebunny/crossref_metadata_2025 huggingface dataset:
PARAMETRIC STUDY OF MULTI-SPOT WELDED LAP SHEAR SPECIMEN FOR TENSILE AND SHEAR STRENGTH
Authors: B. Badole Kisanlal , Mehar Dr. P. G.
Published: September 2021

The effect of number of spots, spot spacing,
squeezing force, welding current, weld time, overlapping
length and sheet thickness on the tensile and shear
strength of two similar galvanized steel sheets are
investigated through experiments using RSM method
and by using software. Similar sheets of galvanized steel
sheets are made by resistance spot welding at different
processing conditions and these joint populations were
tested under lap-shear loading conditions. Specially
fabricated fixture is used to load the lap shear specimen
in the universal testing machine Regression analysis is
done to obtain relationship between shear strength and
selected parameters. The experimental results indicate
that the failure loads of spot welds in lap-shear
specimens increase when number of spot, squeezing
force, welding current and sheet thickness increase for
the given ranges
IoT BASED TOLL BOOTH MANAGER
Authors: Pathak Somesh , Bhat Kartikay , Ahire Vinod , Kedar Hrishikesh
Published: September 2021

There are thousands of vehicles on road these days
and managing these multiple vehicles at a toll booth at the same
time is a very difficult job to be done. At present, the manual toll
system is very inefficient and very time-consuming. Due to this,
there are traffic jams, fights, exchanges of words also. The system
proposed is completely managed on the ‘Internet of Things’
concept based on RFID technology. The Internet server will store
all the users ' required data and their card balance. When the car
driver will arrive at the toll booth, the system at the toll booth
will scan the card. The system then connects to the online server
to check the validation of the card, if the card is valid and will be
having sufficient funds then the particular amount will get
deduced from the card. The system operates a motor to open the
toll gate for a car to pass on deduction of the card balance. The
entire system uses a microcontroller to achieve this purpose. The
WiFi connection connects to the internet through which the
system interacts for online verification. Additionally, all the data
of the vehicles passed will get stored for later reference. Thus, the
system automates the entire process of the toll booth and
terminates the present process of the toll booth collection system.
OBJECT DETECTION SYSTEM FOR THE BLIND WITH VOICEGUIDANCE
Authors: Ravindra Karmarkar Rajeshvaree , Honmane Prof.V.N
Published: September 2021

—As object recognition technology has
developed recently, various technologies have been
applied to autonomousvehicles, robots, and industrial
facilities. However, the benefits ofthese technologies are
not reaching the visually impaired, who need it the
most. This paper proposed an object detection system
for the blind using deep learning technologies.
Furthermore, a voice guidance technique is used to
inform sight impaired persons as to the location of
objects. The object recognition deep learning model
utilizes the You Only Look Once(YOLO) algorithm
and a voice announcement is synthesized using text-tospeech (TTS) to make it easier for the blind to get
information about objects. Asa result, it implements an
efficient object-detection system that helps the blind
find objects in a specific space without help from
others, and the system is analyzed through experiments
to verify performance.
CONTINUOUS IMPROVEMENT IN JUST IN TIME MANUFACTURING (JIT), A SYSTEMATIC LITERATURE REVIEW
Authors: Chikkaballapur Balaji Kruthi , Gopal Poorvika , S Dr. Rashmi
Published: September 2021

The study's initial goal is to become
acquainted with the general Kaizen approach and
the elements required for its successful
implementation.
Methodology: It is critical to understand the
success implementation factors to increase
productivity and achieve value for the research
that has been conducted in many manufacturing
sectors. A systematic literature review (SLR) is
conducted to gain a clear understanding of the
various literature available in the search results for
Continuous Improvements (CI) in Just-in-Time
Manufacturing (JIT). To perform the SRL, 87
articles are accumulated from Google Scholar and
screened according to the inclusion and exclusion
criteria. Another 30 papers have been accepted,
with the majority of them focusing on two research
areas, namely continuous improvement in the
automobile industry and successful
implementation metrics. The 30 papers preferred
are visualized based on the market, country of
origin, variables, and approaches used by the
multiple writers.
Conclusion: After conducting a thorough literature
survey, it was evident that most authors pointed out
the necessity of excellent communication channels,
training, and education for successful CI adoption
in the industries. All the researchers investigated
change, employee and team preparation, and
commitment to change. One study advocated
innovatively using change management tools.
POLITICAL MARKETING PLAN FOR ASPIRING NATIONAL COUNCIL CANDIDATURE
Authors: Gyeltshen Damcho
Published: September 2021

The political marketing plan is mandated to
execute in real life as a document that could benefit the
candidate in political journey of election. The aim of this
research is to develop a marketing plan & brand that serve
as a guiding tool for the candidature by evaluating the
political market through ascertaining of eligible voters in
district level in Bhutan and evaluate the values, needs and
wants of eligible voters there by strategically plan to
develop an effective strategy to fulfil the needs and wants
of electorates. This studies have used both primary data
and secondary data research. As a primary data collection,
an online computer assist survey through google form are
used in understanding the electorates needs and wants,
their problems, the benefits that they expect from the
candidate and ultimately an effective promotion tools that
the candidate could adopt between electorates and the
politician in developing effective marketing strategy. It is
to fulfil the public needs and wants and formulate the plan
and a brand that could possibly serve as a guiding tool for
the national council candidature. The secondary data are
collected from focused group and TDI (Telephone in-depth
interview) in understanding better insight about the public
needs and wants
Subsequently, the content analysis pertaining to webpage,
journals, e-books, annual reports, u-tube are used as a
supplementary data required for the research. Based on
the data collection result, the findings are ascertained and
every results are evaluated and analyzed in depicting the
appropriate target segment and came up with strategic
political plan to promote the candidate as a brand and
product in a market. Through the empirical research, It
indicated that public aspire their political needs as two
core distinct category, the candidate profile and the
candidate pledges. As a candidate profile, they aspire to
have skilled, highly qualified, experience as a mandatory
requirement of candidate and the candid
NANOBOTS: APPLICATIONS IN BIOMEDICAL
Authors: . Shailesh , Kumar Kapil
Published: September 2021

– The utilization of nanotechnology with the
new electronic materials prompted the advancement of
nanorobots. Nanorobots in the nano scale locale are
equipped for entering the phone for conclusion,
treatment and medical procedure. Because of its wide
reach of uses, nanorobots are planned with explicit
materials furthermore, plan innovations. Since the
biocompatible materials are utilized in the plan of
nanorobots, they are synthetically dormant and the
issue of poisonousness is stayed away from. The nano
scale size permits the designated conveyance of
medications to the particular location without
influenced the ordinary encompassing cells. Nanorobots
have the ability to move uninhibitedly in the circulation
system because of the Brownian movement. This paper
plainly clarifies the different biomedical utilizations of
the nanorobots
Taxonomía de la Producción Cinematográfica relacionada con la Educación
Authors: Novoa Ramírez Eliana
Published: September 2021

El estudio propone un registro taxonómico de las principales producciones cinematográficas cuyas narrativas versan sobre la educación y sus actantes: alumnos, profesores, padres de familia, escuela y sociedad. El objetivo es seleccionar y clasificar la producción de películas de ficción cuyo discurso narrativo esté referido a la escuela. La metodología se fundamentó en el enfoque cualitativo descriptivo que utilizó la observación documental, la hermenéutica y el análisis crítico del mensaje audiovisual como técnicas de investigación. Como conclusión se estableció que existe una taxonomía de ocho clases de películas, atendiendo al específico tipo de conflicto principal que se anuda en la narrativa de cada filme.
Relaciones interpersonales y desempeño laboral en hoteles turísticos del departamento de Puno
Authors: Hancco Gomez Miriam Serezade , Carpio Maraza Amira , Laura Castillo Zoraima Julieta , Flores Mamani Emilio
Published: September 2021

Las relaciones interpersonales constituyen un papel crítico en una empresa debido a la interacción con personas que conservan puntos de vista, ideas, percepciones o formación diferentes, las mismas que pueden afectar para bien o mal en el desempeño laboral, por ende, permitir o distraer el logro de los objetivos organizacionales. En ese contexto la investigación tiene como objetivos: analizar cómo son las relaciones interpersonales de los colaboradores de los hoteles del departamento de Puno y determinar el desempeño laboral de los colaboradores de los hoteles del departamento de Puno. Los métodos enmarcan una investigación de enfoque cuantitativo, de alcance exploratorio-descriptivo y diseño no experimental. La población está conformada por 40 hoteles categorizados en tres estrellas, de la misma se ha obtenido una muestra de 16 hoteles, que albergan 84 colaboradores a ser encuestados. La técnica de recolección de datos fue la encuesta y el instrumento el cuestionario para la variable relaciones interpersonales, que contiene 15 preguntas medidas a una escala de Likert y para la variable desempeño laboral se aplicó la evaluación por el método de escala gráfica. El proceso de datos se ha dado a través de la hoja de cálculo Excel y el paquete estadístico SPSS. Mediante este se calculó las frecuencias y porcentajes de cada variable y sus dimensiones. Los resultados permiten concluir que las relaciones interpersonales en los hoteles del departamento de Puno según escala del instrumento utilizado son buenas, así el desempeño laboral de los colaboradores de los hoteles del departamento de Puno es bueno según la escala grafica.
Kyrgyz and English Nomination of Children
Authors: Tazhibaeva A. , Kudaiberdi kyzy O.
Published: September 2021

Research relevance: this article examines the units of children nominations in the linguistic picture of Kyrgyz people world. The nominations of the concept child, in the language indicating certain aspects of this concept, reflect its real characteristics in different directions. Research objectives: study of children Kyrgyz and English nominations. Research materials and methods: in this work authors used methods based on the analysis of linguistic representations of the concept of a child and the ways of organizing the identified nominations of children into groups. Research results: certain nominations contain indications of the social characteristics in the child’s image, including the child’s status in the family and the child’s belonging to social institutions, in addition, nominations describing the birth conditions, life and family education received by the child were highlighted. Conclusions: the concept under study has relevant features corresponding to two different linguocultures.
The Effect of Financial Distress, Firm Size, Leverage and Litigation Risk on The Application of Accounting Conservatism In Manufacturing Companies Listed In Indonesia Stock Exchange
Authors: Septriana Ira , Triyono Hermawan , Prajanto Agung
Published: September 2021

This research aims to analyze the effect of financial distress, firm size, leverage, and litigation risk on implementing the accounting conservatism of manufacturing companies in Indonesia. The population in this research is manufacturing companies listed on the Indonesia Stock Exchanged (IDX) over 2014-2018. Research sample selection used the purposive sampling method. Obtained company data that meet the research criteria as many as 169 companies, so that the total research data is 149 data. The analysis methods in this research are multiple regression analysis. Based on the test results of the research conclude that variables of the board of financial distress, firm size, and litigation risk have no effect on accounting conservatism implemented of manufacturing companies. Meanwhile, the variable of leverage affects the accounting conservatism's implemented by manufacturing companies.  Keywords: Conservatism Accounting. Financial Distress, Firm Size, Leverage, Litigation Risk
Analysis of the Cellular Composition of Bronchoalveolar Lavage in the Modeling and Treatment of Acute Respiratory Distress Syndrome in Biomodel Mice
Authors: Alimkina O. V. , Petrenko A. E. , Savchenko E. S. , Ogneva N. S. , Taboyakova L. A. , Maksimenko S. V. , Skripkina M. M. , Borisova M. M.
Published: September 2021

This article investigates changes in the cellular composition of bronchoalveolar lavage over time in the modeling of acute respiratory distress syndrome (ARDS) in mice, followed by a single administration of Leutragine. In intact animals, macrophages predominate in bronchoalveolar lavage, which is the physiological norm. When modeling ARDS, neutrophils increase. A single administration of Leutragine leads to a significant reduction in the number of neutrophils and a simultaneous increase in macrophages in 72 hours, thus bringing the cellular composition of lavage to normal.
Neuroimaging of the Intracentral Brain of Cats by Normalization of Electrograms under the Action of Semax
Authors: Fokin Yu. V. , Borisova M. M. , Kharitonov S. Yu.
Published: September 2021

Normalization of FFT-transformed brain electrograms under the action of Semax was performed. The adequacy of the approach to assessing the pharmacodynamics of nootropic drugs exhibiting an activating effect on intracentral relations of the brain was shown. The high-frequency components of encephalograms (the γ-range in particular) were confirmed to be the most important indicators of the effects of psychotropic drugs.
Research Institute for Quality of Life: 30 years of activity on the benefit of Romanian society
Authors: Voicu Mălina
Published: September 2021

The Research Institute for Quality of Life at the Romanian Academy was established in January 1990 with the purpose of conducting research on social change in post-communist Romania. In 2020 RIQL celebrated 30 years of existence, 30 years in the service of Romania society. The celebration held in the aula of the Romanian Academy pointed out the great contribution of the institute to the development of social sciences and of Romanian society over the past three decades.
In memoriam prof. univ. dr. Robert Doron Reisz (13.11.1964-02.02.2020)
Authors: Copilaș Emanuel
Published: September 2021

This short piece represents an evocation of professor Reisz’s generous personality. He was a wonderful and supportive colleague, and he will surely be missed. His professional and moral legacy will nevertheless continue to grow.
Do you like where I brought you? Disenchantment and re-enchantment in Vintilă Mihăilescu’s anthropological teachings (25.05.1951-22.03.2020)
Authors: Iancu Bogdan , Stroe Monica
Published: September 2021

Always provoking, creating disruption, advocating for inclusiveness, questioning elite assumptions and often going against the grain of dominant intellectual voices, Vintilă’s pedagogical lessons remain a source of inspiration for those whom he has shaped as students and influenced as colleagues. The bulk of the students still come from a diversity of professional and educational backgrounds, ranging from the humanities to technical fields. What they seek are answers; what we still aim to provide, in keeping with Vintilă’s legacy, is the ability to ask the right questions and to think anthropologically, no matter the field.
THE FAMILY BACKGROUND - A THEORETICAL APPROACH TO THE FACTORS OF THE CHILD'S SCHOOL SUCCESS
Authors: RUS Mihaela
Published: September 2021

The objective of the study is to approach from a theoretical point of view the importance of the family in the school-family-student triad. The article will focus on the analysis of the role that the family has in the instructive-educational process of the child, focusing on the specialized literature in the field. School and family are the main factors that complete the education of the individual. Each of them contributes through their specific influences to the formation and social integration of the child. The family environment and the school environment are two dimensions of children's lives that make their mark on the formation of their personality. Systematic school education, however, can prove to be ineffective if the family is not involved in carrying out the instructive-educational tasks in the parent-child relationship. Families have decisive educational potential, especially in the first years of a child's life, and strengthen the educational efforts exercised by the school. Thus, working together in interdependence, through combined actions and giving the student an active role in his development, the premises are created for achieving the school success expected by all educational actors: family, school, and student.
Att begripa vad dom begriper
Authors: Samuelsson Joakim
Published: September 2021

Att lära sig matematik innebär att man kommer i kontakt med en mängd olika matematiska begrepp. Genom att tillägna sig begreppen ges eleverna en större möjlighet att förstå matematiken som ska läras. Begreppen hjälper dom att begripa matematiken. Begreppen inom matematiken, liksom inom alla sammanhang har en stor betydelse för möjligheten att förstå och kunna samtala om det man är engagerad i.
Efficient Production of Polyhydroxyalkanoate Through Halophilic Bacteria Utilizing Algal Biodiesel Waste Residue
Authors: Dubey Sonam , Mishra Sandhya
Published: September 2021

The objective of the current work was to investigate the potential of halophilic bacterial isolates for efficient utilization of crude glycerol from algal biodiesel waste into polyhydroxyalkanoates (PHAs) a green plastic. Screening of the isolates was directly done in algal biodiesel waste residue containing solid agar plates supplemented with Nile red. Crude glycerol is a biodiesel waste whose bioconversion into value-added products provides an alternative for efficient management with dual benefit. For the scale-up studies of PHAs, Halomonas spp. especially H. daqingensis was observed as a potential candidate growing well in 3% Algal biodiesel waste residue (ABWR), 5% NaCl supplementation at 35°C within 48 h of incubation. Maximum Cell dry weight (CDW) of 0.362 ± 0.001 g and 0.236 ± 0.003 g PHA was obtained with H. daqingensis when grown in the fermentor with 0.5 vvm air flow rate and 200 rpm containing 3% ABWR supplemented with 5% NaCl at 35°C incubation temperature for 48 h. ABWR can serve as a sole substrate for PHA production at an industrial scale serving two approaches: getting rid of the biodiesel industrial waste containing high amount of glycerol besides using waste replacing commercial substrate thereby reducing the cost of the product.
Coproduction of 5-Aminovalerate and δ-Valerolactam for the Synthesis of Nylon 5 From L-Lysine in Escherichia coli
Authors: Cheng Jie , Tu Wenying , Luo Zhou , Liang Li , Gou Xinghua , Wang Xinhui , Liu Chao , Zhang Guoqiang
Published: September 2021

The compounds 5-aminovalerate and δ-valerolactam are important building blocks that can be used to synthesize bioplastics. The production of 5-aminovalerate and δ-valerolactam in microorganisms provides an ideal source that reduces the cost. To achieve efficient biobased coproduction of 5-aminovalerate and δ-valerolactam in Escherichia coli, a single biotransformation step from L-lysine was constructed. First, an equilibrium mixture was formed by L-lysine α-oxidase RaiP from Scomber japonicus. In addition, by adjusting the pH and H2O2 concentration, the titers of 5-aminovalerate and δ-valerolactam reached 10.24 and 1.82 g/L from 40 g/L L-lysine HCl at pH 5.0 and 10 mM H2O2, respectively. With the optimized pH value, the δ-valerolactam titer was improved to 6.88 g/L at pH 9.0 with a molar yield of 0.35 mol/mol lysine. The ratio of 5AVA and δ-valerolactam was obviously affected by pH value. The ratio of 5AVA and δ-valerolactam could be obtained in the range of 5.63:1–0.58:1 at pH 5.0–9.0 from the equilibrium mixture. As a result, the simultaneous synthesis of 5-aminovalerate and δ-valerolactam from L-lysine in Escherichia coli is highly promising. To our knowledge, this result constitutes the highest δ-valerolactam titer reported by biological methods. In summary, a commercially implied bioprocess developed for the coproduction of 5-aminovalerate and δ-valerolactam using engineered Escherichia coli.
Control of Gene Expression With Quercetin-Responsive Modular Circuits
Authors: Kashiwagi Fernanda Miyuki , Wendler Miranda Brenno , de Oliveira Pedrosa Fabio , de Souza Emanuel Maltempi , Müller-Santos Marcelo
Published: September 2021

Control of gene expression is crucial for several biotechnological applications, especially for implementing predictable and controllable genetic circuits. Such circuits are often implemented with a transcriptional regulator activated by a specific signal. These regulators should work independently of the host machinery, with low gratuitous induction or crosstalk with host components. Moreover, the signal should also be orthogonal, recognized only by the regulator with minimal interference with the host operation. In this context, transcriptional regulators activated by plant metabolites as flavonoids emerge as candidates to control gene expression in bacteria. However, engineering novel circuits requires the characterization of the genetic parts (e.g., genes, promoters, ribosome binding sites, and terminators) in the host of interest. Therefore, we decomposed the QdoR regulatory system of B. subtilis, responsive to the flavonoid quercetin, and reassembled its parts into genetic circuits programmed to have different levels of gene expression and noise dependent on the concentration of quercetin. We showed that only one of the promoters regulated by QdoR worked well in E. coli, enabling the construction of other circuits induced by quercetin. The QdoR expression was modulated with constitutive promoters of different transcriptional strengths, leading to low expression levels when QdoR was highly expressed and vice versa. E. coli strains expressing high and low levels of QdoR were mixed and induced with the same quercetin concentration, resulting in two stable populations expressing different levels of their gene reporters. Besides, we demonstrated that the level of QdoR repression generated different noise levels in gene expression dependent on the concentration of quercetin. The circuits presented here can be exploited in applications requiring adjustment of gene expression and noise using a highly available and natural inducer as quercetin.
Tackling Current Biomedical Challenges With Frontier Biofabrication and Organ-On-A-Chip Technologies
Authors: Celikkin Nehar , Presutti Dario , Maiullari Fabio , Fornetti Ersilia , Agarwal Tarun , Paradiso Alessia , Volpi Marina , Święszkowski Wojciech , Bearzi Claudia , Barbetta Andrea , Zhang Yu Shrike , Gargioli Cesare , Rizzi Roberto , Costantini Marco
Published: September 2021

In the last decades, biomedical research has significantly boomed in the academia and industrial sectors, and it is expected to continue to grow at a rapid pace in the future. An in-depth analysis of such growth is not trivial, given the intrinsic multidisciplinary nature of biomedical research. Nevertheless, technological advances are among the main factors which have enabled such progress. In this review, we discuss the contribution of two state-of-the-art technologies–namely biofabrication and organ-on-a-chip–in a selection of biomedical research areas. We start by providing an overview of these technologies and their capacities in fabricating advancedin vitrotissue/organ models. We then analyze their impact on addressing a range of current biomedical challenges. Ultimately, we speculate about their future developments by integrating these technologies with other cutting-edge research fields such as artificial intelligence and big data analysis.
BRCC3 Promotes Tumorigenesis of Bladder Cancer by Activating the NF-κB Signaling Pathway Through Targeting TRAF2
Authors: Tao Huangheng , Liao Yixiang , Yan Youji , He Zhiwen , Zhou Jiajie , Wang Xinghuan , Peng Jianping , Li Shangze , Liu Tao
Published: September 2021

NF-κB signaling is very important in cancers. However, the role of BRCC3-associated NF-κB signaling activation in bladder cancer remains to be characterized. Western blotting and IHC of tissue microarray were used to confirm the abnormal expression of BRCC3 in bladder cancer. Growth curve, colony formation, soft agar assay and Xenograft model were performed to identify the role of BRCC3 over-expression or knock-out in bladder cancer. Further, RNA-Seq and luciferase reporter assays were used to identify the down-stream signaling pathway. Finally, co-immunoprecipitation and fluorescence confocal assay were performed to verify the precise target of BRCC3. Here, we found that high expression of BRCC3 promoted tumorigenesis through targeting the TRAF2 protein. BRCC3 expression is up-regulated in bladder cancer patients which indicates a negative prognosis. By in vitro and in vivo assays, we found genetic BRCC3 ablation markedly blocks proliferation, viability and migration of bladder cancer cells. Mechanistically, RNA-Seq analysis shows that NF-κB signaling is down-regulated in BRCC3-deficient cells. BRCC3 binds to and synergizes with TRAF2 to activate NF-κB signaling. Our results indicate that high BRCC3 expression activates NF-κB signaling by targeting TRAF2 for activation, which in turn facilitates tumorigenesis in bladder cancer. This finding points to BRCC3 as a potential target in bladder cancer patients.
β-Hairpin Peptide Mimics Decrease Human Islet Amyloid Polypeptide (hIAPP) Aggregation
Authors: Lesma Jacopo , Bizet Faustine , Berardet Corentin , Tonali Nicolo , Pellegrino Sara , Taverna Myriam , Khemtemourian Lucie , Soulier Jean-Louis , van Heijenoort Carine , Halgand Frédéric , Ha-Duong Tâp , Kaffy Julia , Ongeri Sandrine
Published: September 2021

Amyloid diseases are degenerative pathologies, highly prevalent today because they are closely related to aging, that have in common the erroneous folding of intrinsically disordered proteins (IDPs) which aggregate and lead to cell death. Type 2 Diabetes involves a peptide called human islet amyloid polypeptide (hIAPP), which undergoes a conformational change, triggering the aggregation process leading to amyloid aggregates and fibers rich in β-sheets mainly found in the pancreas of all diabetic patients. Inhibiting the aggregation of amyloid proteins has emerged as a relevant therapeutic approach and we have recently developed the design of acyclic flexible hairpins based on peptidic recognition sequences of the amyloid β peptide (Aβ1–42) as a successful strategy to inhibit its aggregation involved in Alzheimer’s disease. The present work reports the extension of our strategy to hIAPP aggregation inhibitors. The design, synthesis, conformational analyses, and biophysical evaluations of dynamic β-hairpin like structures built on a piperidine-pyrrolidine β-turn inducer are described. By linking to this β-turn inducer three different arms (i) pentapeptide, (ii) tripeptide, and (iii) α/aza/aza/pseudotripeptide, we demonstrate that the careful selection of the peptide-based arms from the sequence of hIAPP allowed to selectively modulate its aggregation, while the peptide character can be decreased. Biophysical assays combining, Thioflavin-T fluorescence, transmission electronic microscopy, capillary electrophoresis, and mass spectrometry showed that the designed compounds inhibit both the oligomerization and the fibrillization of hIAPP. They are also capable to decrease the aggregation process in the presence of membrane models and to strongly delay the membrane-leakage induced by hIAPP. More generally, this work provides the proof of concept that our rational design is a versatile and relevant strategy for developing efficient and selective inhibitors of aggregation of amyloidogenic proteins.
Primordial Germ Cell Specification in Vertebrate Embryos: Phylogenetic Distribution and Conserved Molecular Features of Preformation and Induction
Authors: Hansen Christina L. , Pelegri Francisco
Published: September 2021

The differentiation of primordial germ cells (PGCs) occurs during early embryonic development and is critical for the survival and fitness of sexually reproducing species. Here, we review the two main mechanisms of PGC specification, induction, and preformation, in the context of four model vertebrate species: mouse, axolotl,Xenopusfrogs, and zebrafish. We additionally discuss some notable molecular characteristics shared across PGC specification pathways, including the shared expression of products from three conserved germline gene families,DAZ(Deleted in Azoospermia) genes,nanos-related genes, andDEAD-box RNA helicases. Then, we summarize the current state of knowledge of the distribution of germ cell determination systems across kingdom Animalia, with particular attention to vertebrate species, but include several categories of invertebrates – ranging from the “proto-vertebrate” cephalochordates to arthropods, cnidarians, and ctenophores. We also briefly highlight ongoing investigations and potential lines of inquiry that aim to understand the evolutionary relationships between these modes of specification.
An Integrative Network Science and Artificial Intelligence Drug Repurposing Approach for Muscle Atrophy in Spaceflight Microgravity
Authors: Manian Vidya , Orozco-Sandoval Jairo , Diaz-Martinez Victor
Published: September 2021

Muscle atrophy is a side effect of several terrestrial diseases which also affects astronauts severely in space missions due to the reduced gravity in spaceflight. An integrative graph-theoretic network-based drug repurposing methodology quantifying the interplay of key gene regulations and protein–protein interactions in muscle atrophy conditions is presented. Transcriptomic datasets from mice in spaceflight from GeneLab have been extensively mined to extract the key genes that cause muscle atrophy in organ muscle tissues such as the thymus, liver, and spleen. Top muscle atrophy gene regulators are selected by Bayesian Markov blanket method and gene–disease knowledge graph is constructed using the scalable precision medicine knowledge engine. A deep graph neural network is trained for predicting links in the network. The top ranked diseases are identified and drugs are selected for repurposing using drug bank resource. A disease drug knowledge graph is constructed and the graph neural network is trained for predicting new drugs. The results are compared with machine learning methods such as random forest, and gradient boosting classifiers. Network measure based methods shows that preferential attachment has good performance for link prediction in both the gene–disease and disease–drug graphs. The receiver operating characteristic curves, and prediction accuracies for each method show that the random walk similarity measure and deep graph neural network outperforms the other methods. Several key target genes identified by the graph neural network are associated with diseases such as cancer, diabetes, and neural disorders. The novel link prediction approach applied to the disease drug knowledge graph identifies the Monoclonal Antibodies drug therapy as suitable candidate for drug repurposing for spaceflight induced microgravity. There are a total of 21 drugs identified as possible candidates for treating muscle atrophy. Graph neural network is a promising deep learning architecture for link prediction from gene–disease, and disease–drug networks.
miR-29b-3p Increases Radiosensitivity in Stemness Cancer Cells via Modulating Oncogenes Axis
Authors: Pan Dong , Du Yarong , Li Rong , Shen Aihua , Liu Xiaodong , Li Chuanyuan , Hu Burong
Published: September 2021

Radioresistance conferred by cancer stem cells (CSCs) is the principal cause of the failure of cancer radiotherapy. Eradication of CSCs is a prime therapeutic target and a requirement for effective radiotherapy. Three dimensional (3D) cell-cultured model could mimic the morphology of cellsin vivoand induce CSC properties. Emerging evidence suggests that microRNAs (miRNAs) play crucial roles in the regulation of radiosensitivity in cancers. In this study, we aim to investigate the effects of miRNAs on the radiosensitivity of 3D cultured stem-like cells. Using miRNA microarray analysis in 2D and 3D cell culture models, we found that the expression of miR-29b-3p was downregulated in 3D cultured A549 and MCF7 cells compared with monolayer (2D) cells. Clinic data analysis from The Cancer Genome Atlas database exhibited that miR-29b-3p high expression showed significant advantages in lung adenocarcinoma and breast invasive carcinoma patients’ prognosis. The subsequent experiments proved that miR-29b-3p overexpression decreased the radioresistance of cells in 3D culture and tumorsin vivothrough interfering kinetics process of DNA damage repair and inhibiting oncogenes RBL1, PIK3R1, AKT2, and Bcl-2. In addition, miR-29b-3p knockdown enhanced cancer cells invasion and migration capability. MiR-29b-3p overexpression decreased the stemness of 3D cultured cells. In conclusion, our results demonstrate that miR-29b-3p could be a sensitizer of radiation killing in CSC-like cellsviainhibiting oncogenes expression. MiR-29b-3p could be a novel therapeutic candidate target for radiotherapy.
Platelet-Derived Microvesicles Promote VSMC Dedifferentiation After Intimal Injury via Src/Lamtor1/mTORC1 Signaling
Authors: Liu Ji-Ting , Bao Han , Fan Yang-Jing , Li Zi-Tong , Yao Qing-Ping , Han Yue , Zhang Ming-Liang , Jiang Zong-Lai , Qi Ying-Xin
Published: September 2021

Phenotypic switch of vascular smooth muscle cells (VSMCs) is important in vascular remodeling which causes hyperplasia and restenosis after intimal injury. Platelets are activated at injured intima and secrete platelet-derived microvesicles (PMVs). Herein, we demonstrated the role of PMVs in VSMC phenotypic switch and the potential underlying mechanisms. In vivo, platelets were locally adhered and activated at intimal injury site, while Lamtor1 was promoted and VSMCs were dedifferentiated. PMVs, collected from collagen-activated platelets in vitro which mimicked collagen exposure during intimal injury, promoted VSMC dedifferentiation, induced Lamtor1 expression, and activated mTORC1 signaling, reflected by the phosphorylation of two downstream targets, i.e., S6K and 4E-BP1. Knockdown of Lamtor1 with small interfering RNA attenuated these processes induced by PMVs. Based on the previously published proteomic data, Ingenuity Pathway Analysis revealed that Src may participate in regulating effects of PMVs. Src inhibitor significantly reversed the effects of PMVs on VSMC dedifferentiation, Lamtor1 expression and mTORC1 activation. Furthermore, in SMC-specific Lamtor1 knockout mice, intimal hyperplasia was markedly attenuated after intimal injury compared with the wild type. Our data suggested that PMVs secreted by activated platelets promoted VSMC dedifferentiation via Src/Lamtor1/mTORC1 signaling pathway. Lamtor1 may be a potential therapeutic target for intimal hyperplasia after injury.
Synthesis and Mesomorphic and Electrical Investigations of New Furan Liquid Crystal Derivatives
Authors: Al-Mutabagani Laila A. , Alshabanah Latifah A. , Gomha Sobhi M. , Abolibda Tariq Z. , Shaban Mohamed , Ahmed Hoda A.
Published: September 2021

New homologues set liquid crystalline materials, based on furfural derivatives, namely, (E)-4-((furan-2-ylmethylene)amino)phenyl 4-alkoxybenzoate (Fn), were synthesized and investigated for their mesomorphic and optical characteristics. The prepared homologues series constitutes three derivatives that bear different terminal flexible alkyl chain lengths that vary between 6 and 12 carbons and attached to the phenyl ring linked to the ester group. A furfural moiety is introduced into the other terminal of the molecular structure. Mesomorphic characterizations of the prepared derivatives were measured using differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Molecular structures were elucidated via elemental analyses, FTIR, and NMR spectroscopy. DSC and POM showed that all the synthesized furfural derivatives are purely nematogenic, exhibiting an enantiotropic nematic (N) mesophase, except for the longest chain derivative (F12) that is dimorphic possessing a monotropic smectic A phase and an enantiotropic N mesophase. Results indicated that the incorporation of the heterocyclic furfural ring into the molecular skeleton affected both the mesophase range and stability of investigated homologue. Analysis of the optical properties revealed that the shortest chain compound (F6) possesses two direct band gaps, at 2.73 and 3.64 eV, in addition to higher absorption than the higher homologues, F10 and F12. On the other hand, all the synthesized homologues (Fn) showed Ohmic behaviors, with electric resistances in the GΩ range. The values of the electrical resistances are 103.71, 12.91, and 196.85 GΩ at 0.05 V for F6, F10, and F12, respectively.
Atomic-Scale Design of High-Performance Pt-Based Electrocatalysts for Oxygen Reduction Reaction
Authors: Ying Jie
Published: September 2021

Fuel cells are regarded as one of the most promising energy conversion devices because of their high energy density and zero emission. Development of high-performance Pt-based electrocatalysts for the oxygen reduction reaction (ORR) is vital to the commercial application of these fuel cell devices. Herein, we review the most significant breakthroughs in the development of high-performance Pt-based ORR electrocatalysts in the past decade. Novel and preferred nanostructures, including biaxially strained core–shell nanoplates, ultrafine jagged nanowires, nanocages with subnanometer-thick walls and nanoframes with three-dimensional surfaces, for excellent performance in ORR are emphasized. Important effects of strain, particle proximity, and surface morphology are fully discussed. The remaining changes and prospective research directions are also proposed.
An In Vitro Mixed Infection Model With Commensal and Pathogenic Staphylococci for the Exploration of Interspecific Interactions and Their Impacts on Skin Physiology
Authors: Kohda Katsunori , Li Xuan , Soga Naoki , Nagura Risa , Duerna Tie , Nakajima Saeko , Nakagawa Ichiro , Ito Masakazu , Ikeuchi Akinori
Published: September 2021

The skin microbiota has been recognized to play an integral role in the physiology and pathology of the skin. The crosstalk between skin and the resident microbes has been extensively investigated using two-dimensional (2D) and three-dimensional (3D) cell cultures in vitro; however, skin colonization by multiple species and the effects of interspecific interactions on the structure and function of skin remains to be elucidated. This study reports the establishment of a mixed infection model, incorporating both commensal (Staphylococcus epidermidis) and pathogenic (Staphylococcus aureus) bacteria, based on a 3D human epidermal model. We observed that co-infecting the 3D epidermal model with S. aureus and S. epidermidis restricted the growth of S. aureus. In addition, S. aureus induced epidermal cytotoxicity, and the release of proinflammatory cytokines was attenuated by the S. aureus-S. epidermidis mixed infection model. S. epidermidis also inhibited the invasion of the deeper epidermis by S. aureus, eliciting protective effects on the integrity of the epidermal barrier. This 3D culture-based mixed infection model would be an effective replacement for existing animal models and 2D cell culture approaches for the evaluation of diverse biotic and abiotic factors involved in maintaining skin health.
Visit-to-Visit Fasting Glucose Variability in Young Adulthood and Cardiac Structure and Function at Midlife: The CARDIA Study
Authors: Xiong Zhenyu , Xie Peihan , Li Jiaying , Chen Zhi-chong , Lin Yifen , Liu Menghui , Zhang Shaozhao , Zhong Xiangbin , Zhou Huimin , Zhuang Xiaodong , Liao Xinxue
Published: September 2021

Glycemic variability was found associated with left ventricular structure and function in type 2 diabetes. But it is still unclear that whether the greater visit-to-visit fasting glucose (FG) variability in young adulthood among the community population is associated with cardiac function alteration and cardiac remodeling at midlife. The community-based prospective cohort study of Coronary Artery Risk in Young Adult (CARDIA) recruited young participants at the baseline age of 18–30 years during the period of 1985–1986 (Year 0). FG was measured at Year 0, 2, 10, 15, 20, and 25. The echocardiographic evaluation of cardiac structure and function was conducted at year 25. A total of 2,600 young adults mean (SD) aged at 24.9 years (3.6) of which 57.3% were women and 46.7% were African Americans had been included in the study. After multivariable adjusted, higher SD of mean FG (SDFG) is associated with lower early peak diastolic septal mitral annular velocity (e') (β [SE], −0.214 [0.080], P < 0.01) and higher E/e' (β [SE], 0.307 [0.094], P < 0.01), and higher coefficient of variation of the mean FG (CVFG) is also associated with lower e' (β [SE], −0.141[0.066], P < 0.05) and higher E/e' (β [SE], 0.204 [0.078], P < 0.01). The higher average real variation of mean FG (ARVFG) is associated with higher E/e' (β [SE], 0.178 [0.085], P < 0.05) and higher left ventricular mass index (LVMI) (β [SE], 1.240 [0.618], P < 0.05). The higher FG variability in young adulthood is associated with the subclinical change of left ventricular (LV) diastolic function at midlife.
Systems of Care in Cardiogenic Shock
Authors: Alvarez Villela Miguel , Clark Rachel , William Preethi , Sims Daniel B. , Jorde Ulrich P.
Published: September 2021

Outcomes for cardiogenic shock (CS) patients remain relatively poor despite significant advancements in primary percutaneous coronary interventions (PCI) and temporary circulatory support (TCS) technologies. Mortality from CS shows great disparities that seem to reflect large variations in access to care and physician practice patterns. Recent reports of different models to standardize care in CS have shown considerable potential at improving outcomes. The creation of regional, integrated, 3-tiered systems, would facilitate standardized interventions and equitable access to care. Multidisciplinary CS teams at Level I centers would direct care in a hub-and-spoke model through jointly developed protocols and real-time shared decision making. Levels II and III centers would provide early access to life-saving therapies and safe transfer to designated hub centers. In regions with large geographical distances, the implementation of telemedicine-cardiac intensive care unit (CICU) care can be an important resource for the creation of effective systems of care.
Disentangling the Effects of SFON (Spontaneous Focusing on Numerosity) and Symbolic Number Skills on the Mathematical Achievement of First Graders. A Longitudinal Study
Authors: Gloor Noemi , Leuenberger Delia , Moser Opitz Elisabeth
Published: September 2021

Research has established that Spontaneous Focusing on Numerosity (SFON) and symbolic number skills (e.g., counting out loud, counting objects, linking small magnitudes and numbers) are predictors of mathematical achievement in primary school. However, little is known about the relationship between SFON and symbolic number skills, or whether one of these factors is more influential on a child’s subsequent mathematical achievement. This study investigated the effect of SFON and symbolic number skills on mathematical achievement at the end of Grade 1 by controlling for first language, gender, working memory and nonverbal IQ. Participants wereN= 1,279 first graders. SFON, symbolic number skills and control variables (first language, gender, working memory, and nonverbal IQ) were measured at the beginning of Grade 1. SFON was assessed with a verbally-based task. Data on mathematical achievement was collected at the end of Grade 1. Descriptive statistics demonstrated that the children’s SFON was relatively low at the beginning of Grade 1. Structural equation modeling was used to examine the relationship between SFON, symbolic number skills and mathematical achievement at the end of Grade 1. The results revealed a weakly significant correlation between SFON and symbolic number skills. SFON and symbolic number skills were significant predictors of mathematical achievement at the end of Grade 1. However, the effect of symbolic number skills on mathematical achievement was greater than the effect of SFON. It is therefore concluded that numerical skills are more important than SFON for predicting mathematical achievement over the course of first grade.
Brain Metastases From Differentiated Thyroid Carcinoma: A Retrospective Study of 22 Patients
Authors: Wu Tong , Jiao Zan , Li Yixuan , Peng Jin , Yao Fan , Chen Weichao , Yang Ankui
Published: September 2021

Background

Brain metastasis from differentiated thyroid cancer has followed a similar increasing trend to that of thyroid cancer in recent years. However, the characteristics and treatments for brain metastases are unclear. The aim of this study was to understand this disease by analyzing patients with brain metastases from differentiated thyroid cancer (DTC).

Methods

Between 2000 and 2020, the database of the Sun Yat-sen University Cancer Center was searched for differentiated thyroid cancer patients. We identified a cohort of 22 patients with brain metastases. The characteristics of the patients, histological features, treatments, and time of death were reviewed. The overall survival (OS) rate was calculated using the Kaplan Meier method. Survival curves of different subgroups were compared according to baseline characteristics and treatments received.

Results

A total of 22 (1.09%) out of 2013 DTC patients in the Sun Yat-sen University Cancer Center database were identified as having brain metastases. The overall median survival time was 17.5 months (range from 1–60 months) after diagnosis of brain metastasis. Performance statue (PS), tumor site, and neurosurgery impacted survival, according to Kaplan-Meier analysis. Prognosis of skull metastasis was superior to that of intracranial types. Neurosurgery was the only type of treatment that had an impact on patient OS.

Conclusions

Brain metastasis from differentiated thyroid cancer has a poor prognosis. However, it can be improved by comprehensive treatment. PS of the patients can greatly affect survival. Skull metastases have improved prognosis over intracranial types. Radioiodine therapy (RAIT) appears to effectively improve the prognosis of patients with skull metastases from DTC.