bluuebunny/crossref_metadata_2025 huggingface dataset:
Too Cute to Kill? The Need for Objective Measurements of Quality of Life
Authors: Wolfensohn Sarah
Published: June 2020

The recognition of animal suffering is influenced by cultural and societal prejudices and the cuteness of an animal leads to bias in the way it is treated. It is important to consider the animal’s behaviour and its environment—not just its physical condition—when assessing its quality of life. The Animal Welfare Assessment Grid (AWAG) is a useful tool for this purpose. The AWAG offers an evidence-based tool for continual welfare assessment, using technology where appropriate, such as digital activity recording, to facilitate decision-making and lead to improvements in the animals’ quality of life. It is highly adaptable to any species by assessing the four parameters of physical health, psychological wellbeing, environmental quality, and clinical and management procedural events. The outcome of assessing welfare should be action to improve it. Societal ethics and policy-making lead to legislation balancing the values we hold for different species. Influencing policy development in such matters as animal welfare, ecological conservation, and risks to humans requires a focus on public attitudes to, and understanding of, science, as well as consideration of potential unforeseen consequences of the social/environmental/economic impacts of policies.
Collision Avoidance Method Using Vector-Based Mobility Model in TDMA-Based Vehicular Ad Hoc Networks
Authors: Bang Jung-Hyun , Lee Jung-Ryun
Published: June 2020

The rapid development of wireless technology has accelerated the development of Vehicular Ad Hoc Networks (VANETs) to support accident prevention and the safety of a vehicle driver. VANET is a form of Mobile Ad Hoc Network (MANET), and it differs from MANET in that the network topology of a VANET changes dynamically in response to the high mobility of a vehicle and the unstable link quality due to various types of road patterns. Since most access and merging conflicts occur due to vehicle movement patterns and traffic conditions, the collision rate can be reduced if each vehicle can predict the location, movement direction, and resource occupancy information of other vehicles. In this paper, we propose a collision avoidance method based on the vehicle mobility prediction model in TDMA-based VANET. The proposed algorithm allocates time-slots of TDMA to avoid access and merging collisions by predicting the mobility of nearby vehicles using control time-slot occupancy information, vehicle ID, hop information, vehicle movement direction, and longitude and latitude of a vehicle. Simulation results show that the proposed algorithm can reduce access and merging collision rates compared with other legacy algorithms, and the performance gain of the proposed algorithm is enhanced in road environments when traffic density is high and where vehicles have high mobility and change their travel directions frequently.
Value-Oriented and Ethical Technology Engineering in Industry 5.0: A Human-Centric Perspective for the Design of the Factory of the Future
Authors: Longo Francesco , Padovano Antonio , Umbrello Steven
Published: June 2020

Although manufacturing companies are currently situated at a transition point in what has been called Industry 4.0, a new revolutionary wave—Industry 5.0—is emerging as an ‘Age of Augmentation’ when the human and machine reconcile and work in perfect symbiosis with one another. Recent years have indeed assisted in drawing attention to the human-centric design of Cyber-Physical Production Systems (CPPS) and to the genesis of the ‘Operator 4.0’, two novel concepts that raise significant ethical questions regarding the impact of technology on workers and society at large. This paper argues that a value-oriented and ethical technology engineering in Industry 5.0 is an urgent and sensitive topic as demonstrated by a survey administered to industry leaders from different companies. The Value Sensitive Design (VSD) approach is proposed as a principled framework to illustrate how technologies enabling human–machine symbiosis in the Factory of the Future can be designed to embody elicited human values and to illustrate actionable steps that engineers and designers can take in their design projects. Use cases based on real solutions and prototypes discuss how a design-for-values approach aids in the investigation and mitigation of ethical issues emerging from the implementation of technological solutions and, hence, support the migration to a symbiotic Factory of the Future.
Revealing the Impacts of Passive Cooling Techniques on Building Energy Performance: A Residential Case in Hong Kong
Authors: Yu Chuan-Rui , Guo Han-Sen , Wang Qian-Cheng , Chang Rui-Dong
Published: June 2020

Environmental concerns and growing energy costs raise the importance of sustainable development and energy conservation. The building sector accounts for a significant portion of total energy consumption. Passive cooling techniques provide a promising and cost-efficient solution to reducing the energy demand of buildings. Based on a typical residential case in Hong Kong, this study aims to analyze the integration of various passive cooling techniques on annual and hourly building energy demand with whole building simulation. The results indicate that infiltration and insulation improvement are effective in regard to energy conservation in buildings, while the effectiveness of variations in building orientation, increasing natural ventilation rate, and phase change materials (PCM) are less significant. The findings will be helpful in the passive house standard development in Hong Kong and contribute to the further optimization work to realize both energy efficiency and favorably built environments in residential buildings.
Agricultural Water Vulnerability under Climate Change in Cyprus
Authors: Papadopoulou Maria , Charchousi Despoina , Spanoudaki Katerina , Karali Anna , Varotsos Konstantinos , Giannakopoulos Christos , Markou Marinos , Loizidou Maria
Published: June 2020

This study focuses on the quantification of climate change (CC) effects on agricultural water availability in Cyprus. Projections of climatic variables, based on Regional Climate Models (RCMs) forced by the Representative Concentration Pathways (RCPs) 4.5 and 8.5, were used as CC driving forces affecting water availability. Groundwater flow models were developed for specific high-interest agricultural areas in Larnaca and Paphos to assess the CC impacts on these groundwater systems, while the Standardized Precipitation–Evapotranspiration Index (SPEI) analysis was also adopted, for the first time in Cyprus, to assess future trends of water reservoir storage under the projected climatic conditions. Considering the current cultivation and irrigation practices, a decrease in groundwater level close to 1 m and further inland seawater intrusion in Larnaca aquifers are expected, while in Paphos’ aquifers, the predicted water table fluctuations are not significant. Additionally, SPEI values at the Asprokemos and Kouris dams are correlated with water storage measurements, showing that a SPEI downward trend observed in these reservoirs could set off an alarm to the water authorities with respect to water availability as more severe drought events are expected in the future. The expected pressure on surface waters imposes the need for an improved water management plan that will not depend on the further exploitation of groundwater.
A Pilot Study on Linking Tissue Mechanics with Load-Dependent Collagen Microstructures in Porcine Tricuspid Valve Leaflets
Authors: Hudson Luke T. , Jett Samuel V. , Kramer Katherine E. , Laurence Devin W. , Ross Colton J. , Towner Rheal A. , Baumwart Ryan , Lim Ki Moo , Mir Arshid , Burkhart Harold M. , Wu Yi , Lee Chung-Hao
Published: June 2020

The tricuspid valve (TV) is composed of three leaflets that coapt during systole to prevent deoxygenated blood from re-entering the right atrium. The connection between the TV leaflets’ microstructure and the tissue-level mechanical responses has yet to be fully understood in the TV biomechanics society. This pilot study sought to examine the load-dependent collagen fiber architecture of the three TV leaflets, by employing a multiscale, combined experimental approach that utilizes tissue-level biaxial mechanical characterizations, micro-level collagen fiber quantification, and histological analysis. Our results showed that the three TV leaflets displayed greater extensibility in the tissues’ radial direction than in the circumferential direction, consistently under different applied biaxial tensions. Additionally, collagen fibers reoriented towards the direction of the larger applied load, with the largest changes in the alignment of the collagen fibers under radially-dominant loading. Moreover, collagen fibers in the belly region of the TV leaflets were found to experience greater reorientations compared to the tissue region closer to the TV annulus. Furthermore, histological examinations of the TV leaflets displayed significant regional variation in constituent mass fraction, highlighting the heterogeneous collagen microstructure. The combined experimental approach presented in this work enables the connection of tissue mechanics, collagen fiber microstructure, and morphology for the TV leaflets. This experimental methodology also provides a new research platform for future developments, such as multiscale models for the TVs, and the design of bioprosthetic heart valves that could better mimic the mechanical, microstructural, and morphological characteristics of the native tricuspid valve leaflets.
Caudatin Isolated from Cynanchum auriculatum Inhibits Breast Cancer Stem Cell Formation via a GR/YAP Signaling
Authors: Zhen Xing , Choi Hack Sun , Kim Ji-Hyang , Kim Su-Lim , Liu Ren , Ko Yu-Chan , Yun Bong-Sik , Lee Dong-Sun
Published: June 2020

In the complex tumor microenvironment, cancer stem cells (CSCs), a rare population of cells, are responsible for malignant tumor initiation, metastasis, drug resistance and recurrence. Controlling breast CSCs (BCSCs) using natural compounds is a novel potential therapeutic strategy for clinical cancer treatment. In this study, a mammosphere assay-guided isolation protocol including silica gel, a C18 column, gel filtration, and high-pressure liquid chromatography was used to isolate an inhibitory compound from Cynanchum auriculatum extracts. The isolated inhibitory compound was identified as caudatin. Caudatin inhibited breast cancer cell proliferation, mammosphere formation and tumor growth. Caudatin decreased the CD44+/CD24− and aldehyde dehydrogenase+ cell proportions and the levels of c-Myc, Oct4, Sox2, and CD44. Caudatin induced ubiquitin (Ub)-dependent glucocorticoid receptor (GR) degradation and blocked subsequent Yes-associated protein (YAP) nuclear accumulation and target gene transcription signals in BCSCs. These results show that the GR/YAP signaling pathway regulates BCSC formation and that caudatin may be a potential chemopreventive agent that targets breast cancer cells and CSCs.
Implications of the Adiponectin System in Non-Small Cell Lung Cancer Patients: A Case-Control Study
Authors: Nigro Ersilia , Perrotta Fabio , Monaco Maria Ludovica , Polito Rita , Pafundi Pia Clara , Matera Maria Gabriella , Daniele Aurora , Bianco Andrea
Published: June 2020

Alterations of adipose tissue occurring in obesity have been recognized as a major risk factor for several cancers. The relationship between adipose tissue and lung cancer, which is the main cancer-related cause of death worldwide, still requires investigation. Perturbations in the adipokine system are likely to interfere with inter-organ crosstalk in lung cancer, which may influence the lung tumor microenvironment. Adiponectin (Acrp30) expression is deregulated in several cancer types. Acrp30 circulates as oligomers with a Low (LMW), Medium (MMW), and High Molecular Weight (HMW), with the latter mediating the main biological effects. Acrp30 acts through AdipoR1 and AdipoR2 receptors. T-cadherin has been described as a non-signaling receptor. This study’s aim was to investigate the regulation of serum Acrp30 and its receptors in sample tissue from non-small cell lung cancer (NSCLC) patients. We recruited 72 NSCLC patients and 60 healthy controls, whom we evaluated in terms of their Acpr30 levels and oligomeric profile. In addition, the expression of AdipoRs in tissues from lung cancer specimens was also measured and compared to coupled healthy lung samples. Our findings show a significant reduction of total Acrp30 levels in NSCLC patients compared to normal subjects, with a specific down-regulation of HMW oligomers. Acrp30 expression was lower in lung adenocarcinoma than other subtypes, regardless of other factors. A significantly higher expression of AdipoR1 was observed, while no differences in R2 and a lower expression of T-cadherin were found in lung cancer specimens compared to normal healthy lung tissues. Involvement of the Acrp30 system in lung cancer may provide new insight into the interaction between adipose tissue and lung and sheds light on its potential ability to influence the lung tumor microenvironment.
Mitochondrial Dysfunction and DNA Damage in the Context of Pathogenesis of Atherosclerosis
Authors: Shemiakova Taisiia , Ivanova Ekaterina , Grechko Andrey V. , Gerasimova Elena V. , Sobenin Igor A. , Orekhov Alexander N.
Published: June 2020

Atherosclerosis is a multifactorial disease of the cardiovascular system associated with aging, inflammation, and oxidative stress. An important role in the development of atherosclerosis play elevated plasma lipoproteins. A number of external factors (smoking, diabetes, infections) can also contribute to the development of the disease. For a long time, atherosclerosis remains asymptomatic, therefore, the search for early markers of the disease is critical for the timely management and better outcomes for patients. Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage appear to connect different aspects of atherosclerosis pathogenesis. To date, multiple lines of research have demonstrated the strong association of mitochondrial dysfunction with the development of various human diseases. Therapies aimed at restoring the mitochondrial function are being actively developed, and are expected to broaden the therapeutic possibilities for several chronic human diseases. The development of such therapies depends on our understanding of the functional roles of different mtDNA variants associated with one or another disorder, and the molecular mechanisms linking mitochondrial dysfunction with a given pathological feature. These questions are, however, challenging and require future intensive research. This review summarizes the recent studies and describes the central processes of the development of atherosclerosis, and shows their relationship with mitochondrial dysfunction. One of the promising therapeutic approaches for future atherosclerosis treatments is the use of mitochondria-targeted antioxidants. Future studies should focus on characterizing the mechanisms of mitochondrial involvement in cardiovascular pathologies to better direct the search for novel therapies.
Microstructural Changes in Motor Functional Conversion Disorder: Multimodal Imaging Approach on a Case
Authors: Longarzo Mariachiara , Cavaliere Carlo , Mele Giulia , Tozza Stefano , Tramontano Liberatore , Alfano Vincenzo , Aiello Marco , Salvatore Marco , Grossi Dario
Published: June 2020

Background: Functional motor conversion disorders are characterized by neurological symptoms unrelated to brain structural lesions. The present study was conducted on a woman presenting motor symptoms causing motor dysfunction, using advanced multimodal neuroimaging techniques, electrophysiological and neuropsychological assessment. Methods. The patient underwent fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) and functional magnetic resonance imaging (fMRI) with both task and resting-state paradigms and was compared with 11 healthy matched controls. To test differences in structural parameters, Bayesian comparison was performed. To test differences in functional parameters, a first- and second-level analysis was performed in task fMRI, while a seed-to-seed analysis to evaluate the connections between brain regions and identify intersubject variations was performed in resting-state fMRI. Results. FDG-PET showed two patterns of brain metabolism, involving the cortical and subcortical structures. Regarding the diffusion data, microstructural parameters were altered for U-shape fibers for the hand and feet regions. Resting-state analysis showed hypoconnectivity between the parahippocampal and superior temporal gyrus. Neurophysiological assessment showed no alterations. Finally, an initial cognitive impairment was observed, paralleled by an anxiety and mild depressive state. Conclusions. While we confirmed no structural alterations sustaining this functional motor disorder, we report microstructural changes in sensory–motor integration for both the hand and feet regions that could functionally support clinical manifestations.
Hereditary Gastric and Breast Cancer Syndromes Related to CDH1 Germline Mutation: A Multidisciplinary Clinical Review
Authors: Corso Giovanni , Montagna Giacomo , Figueiredo Joana , La Vecchia Carlo , Fumagalli Romario Uberto , Fernandes Maria Sofia , Seixas Susana , Roviello Franco , Trovato Cristina , Guerini-Rocco Elena , Fusco Nicola , Pravettoni Gabriella , Petrocchi Serena , Rotili Anna , Massari Giulia , Magnoni Francesca , De Lorenzi Francesca , Bottoni Manuela , Galimberti Viviana , Sanches João Miguel , Calvello Mariarosaria , Seruca Raquel , Bonanni Bernardo
Published: June 2020

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as—(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC).
Role of Anillin in Tumour: From a Prognostic Biomarker to a Novel Target
Authors: Tuan Nguyen Minh , Lee Chang Hoon
Published: June 2020

Anillin (ANLN), an actin-binding protein, reportedly plays a vital role in cell proliferation and migration, particularly in cytokinesis. Although there have been findings pointing to a contribution of ANLN to the development of cancer, the association of ANLN to cancer remains not fully understood. Here, we gather evidence to determine the applicability of ANLN as a prognostic tool for some types of cancer, and the impact that ANLN has on the hallmarks of cancer. We searched academic repositories including PubMed and Google Scholar to find and review studies related to cancer and ANLN. The conclusion is that ANLN could be a potent target for cancer treatment, but the roles ANLN, other than in cytokinesis and its influence on tumour microenvironment remodeling in cancer development, must be further elucidated, and specific ANLN inhibitors should be found.
ZEB1/miR-200c/AGR2: A New Regulatory Loop Modulating the Epithelial-Mesenchymal Transition in Lung Adenocarcinomas
Authors: Sommerova Lucia , Ondrouskova Eva , Martisova Andrea , Zoumpourlis Vassilis , Galtsidis Sotirios , Hrstka Roman
Published: June 2020

Epithelial-mesenchymal transition (EMT) is a process involved not only in morphogenesis and embryonic development, but also in cancer progression, whereby tumor cells obtain a more aggressive metastatic phenotype. Anterior gradient protein 2 (AGR2) maintains the epithelial phenotype and blocks the induction of EMT, thus playing an undeniable role in tumor progression. However, the mechanism through which AGR2 expression is regulated, not only during EMT, but also in the early stages of cancer development, remains to be elucidated. In the present study, we show an inverse correlation of AGR2 with ZEB1 (zinc finger enhancer binding protein, δEF1) that was verified by analysis of several independent clinical data sets of lung adenocarcinomas. We also identified the ZEB1 binding site within the AGR2 promoter region and confirmed AGR2 as a novel molecular target of ZEB1. The overexpression of ZEB1 decreased the promoter activity of the AGR2 gene, which resulted in reduced AGR2 protein level and the acquisition of a more invasive phenotype of these lung cancer cells. Conversely, silencing of ZEB1 led not only to increased levels of AGR2 protein, but also attenuated the invasiveness of tumor cells. The AGR2 knockout, vice versa, increased ZEB1 expression, indicating that the ZEB1/AGR2 regulatory axis may function in a double negative feedback loop. In conclusion, we revealed for the first time that ZEB1 regulates AGR2 at the transcriptional level, while AGR2 presence contributes to ZEB1 mRNA degradation. Thus, our data identify a new regulatory mechanism between AGR2 and ZEB1, two rivals in the EMT process, tightly associated with the development of metastasis.
How and Why Are Cancers Acidic? Carbonic Anhydrase IX and the Homeostatic Control of Tumour Extracellular pH
Authors: Lee Shen-Han , Griffiths John R.
Published: June 2020

The acidic tumour microenvironment is now recognized as a tumour phenotype that drives cancer somatic evolution and disease progression, causing cancer cells to become more invasive and to metastasise. This property of solid tumours reflects a complex interplay between cellular carbon metabolism and acid removal that is mediated by cell membrane carbonic anhydrases and various transport proteins, interstitial fluid buffering, and abnormal tumour-associated vessels. In the past two decades, a convergence of advances in the experimental and mathematical modelling of human cancers, as well as non-invasive pH-imaging techniques, has yielded new insights into the physiological mechanisms that govern tumour extracellular pH (pHe). In this review, we examine the mechanisms by which solid tumours maintain a low pHe, with a focus on carbonic anhydrase IX (CAIX), a cancer-associated cell surface enzyme. We also review the accumulating evidence that suggest a role for CAIX as a biological pH-stat by which solid tumours stabilize their pHe. Finally, we highlight the prospects for the clinical translation of CAIX-targeted therapies in oncology.
Ubiquitylation-Mediated Fine-Tuning of DNA Double-Strand Break Repair
Authors: Borsos Barbara N. , Majoros Hajnalka , Pankotai Tibor
Published: June 2020

The proper function of DNA repair is indispensable for eukaryotic cells since accumulation of DNA damages leads to genome instability and is a major cause of oncogenesis. Ubiquitylation and deubiquitylation play a pivotal role in the precise regulation of DNA repair pathways by coordinating the recruitment and removal of repair proteins at the damaged site. Here, we summarize the most important post-translational modifications (PTMs) involved in DNA double-strand break repair. Although we highlight the most relevant PTMs, we focus principally on ubiquitylation-related processes since these are the most robust regulatory pathways among those of DNA repair.
Molecular Cloning and Heterologous Expression of Manganese(II)-Oxidizing Enzyme from Acremonium strictum Strain KR21-2
Authors: Tojo Fuyumi , Kitayama Ayumi , Miyata Naoyuki , Okano Kunihiro , Fukushima Jun , Suzuki Ryuichiro , Tani Yukinori
Published: June 2020

Diverse ascomycete fungi oxidize manganese(II) [Mn(II)] and produce Mn(III, IV) oxides in terrestrial and freshwater environments. Although multicopper oxidase (MCO) is considered to be a key catalyst in mediating Mn(II) oxidation in ascomycetes, the responsible gene and its product have not been identified. In this study, a gene, named mco1, encoding Mn(II)-oxidizing MCO from Acremonium strictum strain KR21-2 was cloned and heterologously expressed in the methylotrophic yeast Pichia pastoris. Based on the phylogenetic relationship, similarity of putative copper-binding motifs, and homology modeling, the gene product Mco1 was assigned to a bilirubin oxidase. Mature Mco1 was predicted to be composed of 565 amino acids with a molecular mass of 64.0 kDa. The recombinant enzyme oxidized Mn(II) to yield spherical Mn oxides, several micrometers in diameter. Zinc(II) ions added to the reaction mixture were incorporated by the Mn oxides at a Zn/Mn molar ratio of 0.36. The results suggested that Mco1 facilitates the growth of the micrometer-sized Mn oxides and affects metal sequestration through Mn(II) oxidation. This is the first report on heterologous expression and identification of the Mn(II) oxidase enzyme in Mn(II)-oxidizing ascomycetes. The cell-free, homogenous catalytic system with recombinant Mco1 could be useful for understanding Mn biomineralization by ascomycetes and the sequestration of metal ions in the environment
Irisin Recovers Osteoarthritic Chondrocytes In Vitro
Authors: Vadalà Gianluca , Di Giacomo Giuseppina , Ambrosio Luca , Cannata Francesca , Cicione Claudia , Papalia Rocco , Denaro Vincenzo
Published: June 2020

Physical exercise favors weight loss and ameliorates articular pain and function in patients suffering from osteoarthritis. Irisin, a myokine released upon muscle contraction, has demonstrated to yield anabolic effects on different cell types. This study aimed to investigate the effect of irisin on human osteoarthritic chondrocytes (hOAC) in vitro. Our hypothesis was that irisin would improve hOAC metabolism and proliferation. Cells were cultured in growing media and then exposed to either phosphate-buffered saline (control group) or human recombinant irisin (experimental group). Cell proliferation, glycosaminoglycan content, type II/X collagen gene expression and protein quantification as well as p38/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK), protein kinase B (Akt), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) involvement were evaluated. Furthermore, gene expression of interleukin (IL)-1 and -6, matrix metalloproteinase (MMP)-1 and -13, inducible nitric oxide synthase (iNOS), and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -3 were investigated following irisin exposure. Irisin increased hOAC cell content and both type II collagen gene expression and protein levels, while decreased type X collagen gene expression and protein levels. Moreover, irisin decreased IL-1, IL-6, MMP-1, MMP-13 and iNOS gene expression, while increased TIMP-1 and TIMP-3 levels. These effects seemed to be mediated by inhibition of p38, Akt, JNK and NFκB signaling pathways. The present study suggested that irisin may stimulate hOAC proliferation and anabolism inhibiting catabolism through p38, Akt, JNK, and NFκB inactivation in vitro, demonstrating the existence of a cross-talk between muscle and cartilage.
Identification of Prion Disease-Related Somatic Mutations in the Prion Protein Gene (PRNP) in Cancer Patients
Authors: Kim Yong-Chan , Won Sae-Young , Jeong Byung-Hoon
Published: June 2020

Prion diseases are caused by misfolded prion protein (PrPSc) and are accompanied by spongiform vacuolation of brain lesions. Approximately three centuries have passed since prion diseases were first discovered around the world; however, the exact role of certain factors affecting the causative agent of prion diseases is still debatable. In recent studies, somatic mutations were assumed to be cause of several diseases. Thus, we postulated that genetically unstable cancer tissue may cause somatic mutations in the prion protein gene (PRNP), which could trigger the onset of prion diseases. To identify somatic mutations in the PRNP gene in cancer tissues, we analyzed somatic mutations in the PRNP gene in cancer patients using the Cancer Genome Atlas (TCGA) database. In addition, to evaluate whether the somatic mutations in the PRNP gene in cancer patients had a damaging effect, we performed in silico analysis using PolyPhen-2, PANTHER, PROVEAN, and AMYCO. We identified a total of 48 somatic mutations in the PRNP gene, including 8 somatic mutations that are known pathogenic mutations of prion diseases. We identified significantly different distributions among the types of cancer, the mutation counts, and the ages of diagnosis between the total cancer patient population and cancer patients carrying somatic mutations in the PRNP gene. Strikingly, although invasive breast carcinoma and glioblastoma accounted for a high percentage of the total cancer patient population (9.9% and 5.4%, respectively), somatic mutations in the PRNP gene have not been identified in these two cancer types. We suggested the possibility that somatic mutations of the PRNP gene in glioblastoma can be masked by a diagnosis of prion disease. In addition, we found four aggregation-prone somatic mutations, these being L125F, E146Q, R151C, and K204N. To the best of our knowledge, this is the first specific analysis of the somatic mutations in the PRNP gene in cancer patients.
Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer
Authors: Zhou Chenghui , Fan Ningbo , Liu Fanyu , Fang Nan , Plum Patrick S. , Thieme René , Gockel Ines , Gromnitza Sascha , Hillmer Axel M. , Chon Seung-Hun , Schlösser Hans A. , Bruns Christiane J. , Zhao Yue
Published: June 2020

Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer.
A Microfluidic Single-Cell Cloning (SCC) Device for the Generation of Monoclonal Cells
Authors: Yeh Chuan-Feng , Lin Ching-Hui , Chang Hao-Chen , Tang Chia-Yu , Lai Pei-Tzu , Hsu Chia-Hsien
Published: June 2020

Single-cell cloning (SCC) is a critical step in generating monoclonal cell lines, which are widely used as in vitro models and for producing proteins with high reproducibility for research and the production of therapeutic drugs. In monoclonal cell line generation, the development time can be shortened by validating the monoclonality of the cloned cells. However, the validation process currently requires specialized equipment that is not readily available in general biology laboratories. Here, we report a disposable SCC device, in which single cells can be isolated, validated, and expanded to form monoclonal cell colonies using conventional micropipettes and microscopes. The monoclonal cells can be selectively transferred from the SCC chip to conventional culture plates, using a tissue puncher. Using the device, we demonstrated that monoclonal colonies of actin-GFP (green fluorescent protein) plasmid-transfected A549 cells could be formed in the device within nine days and subsequently transferred to wells in plates for further expansion. This approach offers a cost-effective alternative to the use of specialized equipment for monoclonal cell generation.
Engineering Strategies to Enhance TCR-Based Adoptive T Cell Therapy
Authors: Rath Jan A. , Arber Caroline
Published: June 2020

T cell receptor (TCR)-based adoptive T cell therapies (ACT) hold great promise for the treatment of cancer, as TCRs can cover a broad range of target antigens. Here we summarize basic, translational and clinical results that provide insight into the challenges and opportunities of TCR-based ACT. We review the characteristics of target antigens and conventional αβ-TCRs, and provide a summary of published clinical trials with TCR-transgenic T cell therapies. We discuss how synthetic biology and innovative engineering strategies are poised to provide solutions for overcoming current limitations, that include functional avidity, MHC restriction, and most importantly, the tumor microenvironment. We also highlight the impact of precision genome editing on the next iteration of TCR-transgenic T cell therapies, and the discovery of novel immune engineering targets. We are convinced that some of these innovations will enable the field to move TCR gene therapy to the next level.
Development and Differentiation of Midbrain Dopaminergic Neuron: From Bench to Bedside
Authors: Wang Mengmeng , Ling King-Hwa , Tan Jun , Lu Cheng-Biao
Published: June 2020

Parkinson’s Disease (PD) is a neurodegenerative disorder affecting the motor system. It is primarily due to substantial loss of midbrain dopamine (mDA) neurons in the substantia nigra pars compacta and to decreased innervation to the striatum. Although existing drug therapy available can relieve the symptoms in early-stage PD patients, it cannot reverse the pathogenic progression of PD. Thus, regenerating functional mDA neurons in PD patients may be a cure to the disease. The proof-of-principle clinical trials showed that human fetal graft-derived mDA neurons could restore the release of dopamine neurotransmitters, could reinnervate the striatum, and could alleviate clinical symptoms in PD patients. The invention of human-induced pluripotent stem cells (hiPSCs), autologous source of neural progenitors with less ethical consideration, and risk of graft rejection can now be generated in vitro. This advancement also prompts extensive research to decipher important developmental signaling in differentiation, which is key to successful in vitro production of functional mDA neurons and the enabler of mass manufacturing of the cells required for clinical applications. In this review, we summarize the biology and signaling involved in the development of mDA neurons and the current progress and methodology in driving efficient mDA neuron differentiation from pluripotent stem cells.
PSPC1 Potentiates IGF1R Expression to Augment Cell Adhesion and Motility
Authors: Jen Hsin-Wei , Gu De-Leung , Lang Yaw-Dong , Jou Yuh-Shan
Published: June 2020

Paraspeckle protein 1 (PSPC1) overexpression in cancers is known to be the pro-metastatic switch of tumor progression associated with poor prognosis of cancer patients. However, the detail molecular mechanisms to facilitate cancer cell migration remain elusive. Here, we conducted integrated analysis of human phospho-kinase antibody array, transcriptome analysis with RNA-seq, and proteomic analysis of protein pulldown to study the molecular detail of PSPC1-potentiated phenotypical transformation, adhesion, and motility in human hepatocellular carcinoma (HCC) cells. We found that PSPC1 overexpression re-assembles and augments stress fiber formations to promote recruitment of focal adhesion contacts at the protruding edge to facilitate cell migration. PSPC1 activated focal adhesion-associated kinases especially FAK/Src signaling to enhance cell adhesion and motility toward extracellular matrix (ECM). Integrated transcriptome and gene set enrichment analysis indicated that PSPC1 modulated receptor tyrosine kinase IGF1R involved in the focal adhesion pathway and induction of diverse integrins expression. Knockdown IGF1R expression and treatment of IGF1R inhibitor suppressed PSPC1-induced cell motility. Interestingly, knockdown PSPC1-interacted paraspeckle components including NONO, FUS, and the lncRNA Neat1 abolished PSPC1-activated IGF1R expression. Together, PSPC1 overexpression induced focal adhesion formation and facilitated cell motility via activation of IGF1R signaling. PSPC1 overexpression in tumors could be a potential biomarker of target therapy with IGF1R inhibitor for improvement of HCC therapy.
Parametric Sensitivity of CSTBRs for Lactobacillus casei: Normalized Sensitivity Analysis
Authors: Das Subhashis , Calay Rajnish Kaur , Chowdhury Ranjana
Published: June 2020

In this paper, a sensitivity analysis of a continuous stirred tank bioreactor (CSTBR) was conducted to determine a parametrically sensitive regime. The growth of a lactic acid bacterium, namely, Lactobacillus casei, in a pH-controlled CSTBR was considered as a process model. Normalized objective sensitivities of the minimum pH were determined with respect to input parameters. A generalized criterion for sensitivity was defined for determining the parametric range of three input variables, i.e., dilution rate base stream (θ), base concentration (R), and initial pH (pH0) for maintaining optimal pH range in the reactor. The system exhibits sensitive behavior for θ, R, and pH0, from 0.095 to 0.295, 0 to 0.865, and 4.42 to 4.77, respectively. The critical values of θ, R, and pH0 are 0.0195, 0.48, and 4.6, respectively. The mathematical model can also be used to determine a parametrically sensitive regime for other important parameters, namely, temperature, the concentration of metabolites, and other byproducts. The mathematical tool can also be used in bioreactor design and the improvement of control strategies.
Investigation of Rapid Gas-Sensitive Properties Degradation of ZnO–SnO2 Thin Films Grown on the Glass Substrate
Authors: Petrov Victor V. , Bayan Ekaterina M. , Khubezhov Soslan A. , Varzarev Yuri N. , Volkova Maria G.
Published: June 2020

ZnO–SnO2 films with a thickness of up to 120 nm have been prepared on glass substrates by pyrolysis at 550 °C of three spin-coated organic precursors films. Films of four compositions were obtained on glass substrates. The prepared films were characterized by SEM, XRD, and XPS analysis. Electrophysical studies have shown that the activation energy of the temperature conductivity for all films is equal to 0.75 eV. While the gas-sensitive characteristics by CO treatment in low concentrations at a temperature of 200–300 °C was studied, their rapid degradation was found. Studies using the XPS method have shown that ZnO–SnO2 films contain sodium, which is diffused from the soda-lime glass substrate during the film formation. Studies of XPS spectra after CO treatment have shown that the film surface is almost 50% composed of adsorbed water molecules and OH groups. OH groups are part of the sodium, tin, and zinc hydroxides formed on the surface. In addition, zinc hydrocarbonates are formed on the surface of the films. The detected insoluble compounds lead to the degradation of gas-sensitive properties of ZnO–SnO2 films.
Effect of Action Observation Training on Spasticity, Gross Motor Function, and Balance in Children with Diplegia Cerebral Palsy
Authors: Jeong Young-a , Lee Byoung-Hee
Published: June 2020

This study evaluated the effect of action observation training on spasticity, gross motor function, and balance in children with spastic diplegia cerebral palsy. Eighteen children with cerebral palsy participated in this study. The participants were randomized into the action observation training group (n = 9) and a control group (n = 9). The action observation training group repeatedly practiced the action with their motor skills, while the control group practiced conventional physical therapy. Both groups received 30 min sessions, 3 days a week, for 6 weeks. To confirm the effects of intervention, the spasticity, gross motor function measurement (GMFM), and pediatric reaching test (PRT) were evaluated. The results showed that in the plantar flexor contracture test of both sides, the Modified Tardieu Scale (MTS) of the right side of knee joints, GMFM-B, C, and D were significantly increased between pre- and post-intervention within both groups (p < 0.05). PRT was significantly increased between pre- and post-intervention within the both groups (p < 0.05), and there was a significant difference between the two groups (p < 0.05). These results suggest that action observation training is both feasible and beneficial for improving spasticity, gross motor function, and balance in children with spastic diplegia cerebral palsy.
Assessment of Corrosion Properties of Selected Mineral Waters
Authors: Pietrucha-Urbanik Katarzyna , Skowrońska Dominika , Papciak Dorota
Published: June 2020

This paper presents an analysis of natural mineral waters recognized by EU member states (on the basis of being announced in the Official Journal of the European Union) and originating in Polish territory. For each of these waters, calculations were made in relation to the Langelier saturation index, Ryznar stability index, and indices S1 (effect of chloride and sulfate ions on iron and steel), S2 (effect of nitrate ions on zinc), and S3 (effect of bicarbonate/sulfate ratio on copper). The impact of mineral waters on copper, hot-dip galvanized iron, stainless steel, acid-resistant steel, cast iron, low-alloy steel, and nonalloy steel was assessed on the basis of the indices calculated. The analysis allowed determination of the possibility of these measures being used in assessing the performance of mineral water installations.
Carrier Modulation in Bi2Te3-Based Alloys via Interfacial Doping with Atomic Layer Deposition
Authors: Lim Sang-Soon , Kim Kwang-Chon , Lee Seunghyeok , Park Hyung-Ho , Baek Seung-Hyub , Kim Jin-Sang , Kim Seong Keun
Published: June 2020

The carrier concentration in Bi2Te3-based alloys is a decisive factor in determining their thermoelectric performance. Herein, we propose a novel approach to modulate the carrier concentration via the encapsulation of the alloy precursor powders. Atomic layer deposition (ALD) of ZnO and SnO2 was performed over the Bi2Te2.7Se0.3 powders. After spark plasma sintering at 500 °C for 20 min, the carrier concentration in the ZnO-coated samples decreased, while the carrier concentration in the SnO2-coated samples increased. This trend was more pronounced as the number of ALD cycles increased. This was attributed to the intermixing of the metal ions at the interface. Zn2+ substituted for Bi3+ at the interface acted as an acceptor, while Sn4+ substituted for Bi3+ acted as a donor. This indicates that the carrier concentration can be adjusted depending on the materials deposited with ALD. The use of fine powders changes the carrier concentration more strongly, because the quantity of material deposited increases with the effective surface area. Therefore, the proposed approach would provide opportunities to precisely optimize the carrier concentration for high thermoelectric performance.
In Situ Monitoring Systems of The SLM Process: On the Need to Develop Machine Learning Models for Data Processing
Authors: Yadav Pinku , Rigo Olivier , Arvieu Corinne , Le Guen Emilie , Lacoste Eric
Published: June 2020

In recent years, technological advancements have led to the industrialization of the laser powder bed fusion process. Despite all of the advancements, quality assurance, reliability, and lack of repeatability of the laser powder bed fusion process still hinder risk-averse industries from adopting it wholeheartedly. The process-induced defects or drifts can have a detrimental effect on the quality of the final part, which could lead to catastrophic failure of the finished part. It led to the development of in situ monitoring systems to effectively monitor the process signatures during printing. Nevertheless, post-processing of the in situ data and defect detection in an automated fashion are major challenges. Nowadays, many studies have been focused on incorporating machine learning approaches to solve this problem and develop a feedback control loop system to monitor the process in real-time. In our study, we review the types of process defects that can be monitored via process signatures captured by in situ sensing devices and recent advancements in the field of data analytics for easy and automated defect detection. We also discuss the working principles of the most common in situ sensing sensors to have a better understanding of the process. Commercially available in situ monitoring devices on laser powder bed fusion systems are also reviewed. This review is inspired by the work of Grasso and Colosimo, which presented an overall review of powder bed fusion technology.
Piezoelectric Resonators Excited by Lateral Electric Fields Based on a LiTaO3 Single Crystal
Authors: Shi Hao , Yan Liang , Zheng Yuanzhen , Ma Tingfeng , Wang Mingfei , Huang Bin , Yuan Lili , Wang Ji , Du Jianke , Zhang Han
Published: June 2020

In the present study, piezoelectric resonators under lateral field excitation (LFE) based on a LiTaO3 single crystal are modeled and analyzed. An electrically forced vibration study is employed to acquire the motional capacitance curve and vibration mode shapes. A finite element approach is utilized to investigate the influences of some basic parameters, such as the electrode/plate mass ratio, electrode gap, and electrode width on resonance characteristics. In addition, the design criteria for the gap and width of the electrode of the LiTaO3 LFE resonators are obtained by analyzing the effects of those parameters on vibration strain distributions. The obtained results are essential for designing LFE piezoelectric resonators by using a LiTaO3 single crystal.
Teacher Interventions for Advancing Students’ Mathematical Understanding
Authors: Yao Xiangquan , Manouchehri Azita
Published: June 2020

The relationship between teacher interventions and students’ mathematical thinking has been the subject of inquiry for quite some time. Using the Pirie–Kieren theory for dynamic growth in mathematical understanding, this study documents teacher interventions that support students’ growth toward developing a general understanding of a mathematical idea in a designed learning environment. By studying the interactions of seven middle school students and the teacher-researcher working on a two-week unit on geometric transformations within a dynamic geometry environment, this study identified nine major categories of teacher interventions that support and extend students’ investigations of mathematical ideas around geometric transformations. The typology of teacher interventions reported in this study provides a cognition-based framework for teacher moves that extend and advance students’ mathematical understanding.