bluuebunny/crossref_metadata_2025 huggingface dataset:
Biallelic, Selectable, Knock-in Targeting of CCR5 via CRISPR-Cas9 Mediated Homology Directed Repair Inhibits HIV-1 Replication
Authors: Scheller Stefan H. , Rashad Yasmine , Saleh Fayez M. , Willingham Kurtis A. , Reilich Antonia , Lin Dong , Izadpanah Reza , Alt Eckhard U. , Braun Stephen E.
Published: March 2022

Transplanting HIV-1 positive patients with hematopoietic stem cells homozygous for a 32 bp deletion in the chemokine receptor type 5 (CCR5) gene resulted in a loss of detectable HIV-1, suggesting genetically disrupting CCR5 is a promising approach for HIV-1 cure. Targeting the CCR5-locus with CRISPR-Cas9 was shown to decrease the amount of CCR5 expression and HIV-1 susceptibility in vitro as well as in vivo. Still, only the individuals homozygous for the CCR5-Δ32 frameshift mutation confer complete resistance to HIV-1 infection. In this study we introduce a mechanism to target CCR5 and efficiently select for cells with biallelic frameshift insertion, using CRISPR-Cas9 mediated homology directed repair (HDR). We hypothesized that cells harboring two different selectable markers (double positive), each in one allele of the CCR5 locus, would carry a frameshift mutation in both alleles, lack CCR5 expression and resist HIV-1 infection. Inducing double-stranded breaks (DSB) via CRISPR-Cas9 leads to HDR and integration of a donor plasmid. Double-positive cells were selected via fluorescence-activated cell sorting (FACS), and CCR5 was analyzed genetically, phenotypically, and functionally. Targeted and selected populations showed a very high frequency of mutations and a drastic reduction in CCR5 surface expression. Most importantly, double-positive cells displayed potent inhibition to HIV-1 infection. Taken together, we show that targeting cells via CRISPR-Cas9 mediated HDR enables efficient selection of mutant cells that are deficient for CCR5 and highly resistant to HIV-1 infection.
The Distributional Characteristics of M2 Macrophages in the Placental Chorionic Villi are Altered Among the Term Pregnant Women With Uncontrolled Type 2 Diabetes Mellitus
Authors: Zhang Muqiu , Cui Dong , Yang Huixia
Published: March 2022

Aim

No definite conclusions have been drawn regarding how prolonged exposure to hyperglycemia affects the distribution of macrophages in the placenta, especially in pregnant women with uncontrolled type 2 diabetes mellitus (T2DM). Herein, we explored the distributional characteristics of placental M2 macrophages, including hofbauer cells (HBCs) in the chorionic villi and decidual macrophages, in pregnant women with uncontrolled T2DM.

Methods

Six healthy singleton pregnancies and five uncontrolled T2DM singleton pregnancies were collected. Multicolor immunofluorescence and immunohistochemistry were performed to record M1 macrophages by CD80 and CD86, the general M2 macrophages by CD163, M2a macrophages by CD163 and DG-SIGN, M2b macrophages by CD163 and CD86, and M2c macrophages by CD163 and CD206. Meanwhile, the monocyte marker of CD14 and the general macrophage marker of CD68 were also documented on placenta.

Results

In the chorionic villi and decidua, the most common infiltrated macrophages was the general M2. There were only few M1 and M2b macrophages distributed in the placenta of both the healthy and uncontrolled T2DM groups. The infiltrated degree of M2c macrophages was moderate in chorionic villi and decidua. The uncontrolled T2DM and healthy pregnant women had a comparable amount of M2c macrophages infiltration in the chorionic villi (p = 0.158). Notedly, in both of the healthy and uncontrolled T2DM pregnant women, the predominant subtype of M2 macrophages in the chorionic villi was M2a, where it mainly infiltrated around vessels and syncytiotrophoblasts. The uncontrolled T2DM pregnant women had more M2a macrophage infiltration than the healthy pregnant women (p = 0.016). The M2a macrophages in the decidua of the uncontrolled T2DM group were similar to those of the normal group (p = 0.800). Meanwhile, it was in the chorionic villi but not the decidua, that the CD68+ macrophages and CD14+ M2a macrophages were also elevated in the uncontrolled T2DM group (p = 0.035 and 0.044, respectively).

Conclusion

These results confirmed that the M2 macrophages exhibited increased in the chorionic villi of pregnant women with uncontrolled T2DM. The subsets of M2 macrophages in the placental decidua were similar between uncontrolled T2DM pregnant women and normal groups. It may provide a basis for exploring the functions of different subsets of macrophages in the placental chorionic villi.
Sink or Source: Alternative Roles of Glacier Foreland Meadow Soils in Methane Emission Is Regulated by Glacier Melting on the Tibetan Plateau
Authors: Xing Tingting , Liu Pengfei , Ji Mukan , Deng Yongcui , Liu Keshao , Wang Wenqiang , Liu Yongqin
Published: March 2022

Glacier foreland soils have long been considered as methane (CH4) sinks. However, they are flooded by glacial meltwater annually during the glacier melting season, altering their redox potential. The impacts of this annual flooding on CH4 emission dynamics and methane-cycling microorganisms are not well understood. Herein, we measured in situ methane flux in glacier foreland soils during the pre-melting and melting seasons on the Tibetan Plateau. In addition, high-throughput sequencing and qPCR were used to investigate the diversity, taxonomic composition, and the abundance of methanogenic archaea and methanotrophic bacteria. Our results showed that the methane flux ranged from −10.11 to 4.81 μg·m−2·h−1 in the pre-melting season, and increased to 7.48–22.57 μg·m−2·h−1 in the melting season. This indicates that glacier foreland soils change from a methane sink to a methane source under the impact of glacial meltwater. The extent of methane flux depends on methane production and oxidation conducted by methanogens and methanotrophs. Among all the environmental factors, pH (but not moisture) is dominant for methanogens, while both pH and moisture are not that strong for methanotrophs. The dominant methanotrophs were Methylobacter and Methylocystis, whereas the methanogens were dominated by methylotrophic Methanomassiliicoccales and hydrogenotrophic Methanomicrobiales. Their distributions were also affected by microtopography and environmental factor differences. This study reveals an alternative role of glacier foreland meadow soils as both methane sink and source, which is regulated by the annual glacial melt. This suggests enhanced glacial retreat may positively feedback global warming by increasing methane emission in glacier foreland soils in the context of climate change.
The Emerging Roles of the β-Secretase BACE1 and the Long Non-coding RNA BACE1-AS in Human Diseases: A Focus on Neurodegenerative Diseases and Cancer
Authors: Sayad Arezou , Najafi Sajad , Hussen Bashdar Mahmud , Abdullah Sara Tharwat , Movahedpour Ahmad , Taheri Mohammad , Hajiesmaeili Mohammadreza
Published: March 2022

The β-Secretase (BACE1) is widely studied to be particularly involved in amyloid deposition, a process known as the pathogenic pathway in neurodegenerative diseases. Therefore, BACE1 expression is frequently reported to be upregulated in brain samples of the patients with Alzheimer’s disease (AD). BACE1 expression is regulated by BACE1-AS, a long non-coding RNA (lncRNA), which is transcribed in the opposite direction to its locus. BACE1-AS positively regulates the BACE1 expression, and their expression levels are regulated in physiological processes, such as brain and vascular homeostasis, although their roles in the regulation of amyloidogenic process have been studied further. BACE1-AS dysregulation is reported consistent with BACE1 in a number of human diseases, such as AD, Parkinson’s disease (PD), heart failure (HF), and mild cognitive impairment. BACE1 or less BACE1-AS inhibition has shown therapeutic potentials particularly in decreasing manifestations of amyloid-linked neurodegenerative diseases. Here, we have reviewed the role of lncRNA BACE1 and BACE1-AS in a number of human diseases focusing on neurodegenerative disorders, particularly, AD.
Tuberculous Granuloma: Emerging Insights From Proteomics and Metabolomics
Authors: Sholeye Abisola Regina , Williams Aurelia A. , Loots Du Toit , Tutu van Furth A. Marceline , van der Kuip Martijn , Mason Shayne
Published: March 2022

Mycobacterium tuberculosisinfection, which claims hundreds of thousands of lives each year, is typically characterized by the formation of tuberculous granulomas — the histopathological hallmark of tuberculosis (TB). Our knowledge of granulomas, which comprise a biologically diverse body of pro- and anti-inflammatory cells from the host immune responses, is based mainly upon examination of lungs, in both human and animal studies, but little on their counterparts from other organs of the TB patient such as the brain. The biological heterogeneity of TB granulomas has led to their diverse, relatively uncoordinated, categorization, which is summarized here. However, there is a pressing need to elucidate more fully the phenotype of the granulomas from infected patients. Newly emerging studies at the protein (proteomics) and metabolite (metabolomics) levels have the potential to achieve this. In this review we summarize the diverse nature of TB granulomas based upon the literature, and amplify these accounts by reporting on the relatively few, emerging proteomics and metabolomics studies on TB granulomas. Metabolites (for example, trimethylamine-oxide) and proteins (such as the peptide PKAp) associated with TB granulomas, and knowledge of their localizations, help us to understand the resultant phenotype. Nevertheless, more multidisciplinary ‘omics studies, especially in human subjects, are required to contribute toward ushering in a new era of understanding of TB granulomas – both at the site of infection, and on a systemic level.
18F-FDG PET/CT Imaging: Normal Variants, Pitfalls, and Artifacts Musculoskeletal, Infection, and Inflammation
Authors: Mbakaza Olwethu , Vangu Mboyo-Di-Tamba Willy
Published: March 2022

18F-FDG PET/CT is an integral part of modern-day practice, especially in the management of individuals presenting with malignant processes. The use of this novel imaging modality in oncology has been rapidly evolving. However, due to its detection of cellular metabolism, it is not truly tumor specific. 18F-FDG is also used in the detection of infective and inflammatory disorders. One of the challenges experienced with 18F-FDG PET/CT imaging is the correct differentiation of abnormal uptake that is potentially pathologic, from physiological uptake. Imaging readers, particularly the nuclear physicians, therefore need to be aware of normal physiological variants of uptake, as well as potential pitfalls and artifacts when imaging with 18F-FDG. This is true for musculoskeletal uptake, where more than often, infective and inflammatory processes should not be mistaken for malignancy. This article aims to provide a pictorial review and analysis of cases that depict musculoskeletal, infective, and inflammatory uptake as normal variants, pitfalls, and artifacts on 18F-FDG PET/CT imaging. The impact of this article is to help in the minimizing of poor imaging quality, erroneous interpretations and diminishes misdiagnoses that may impact on the adequate management of patients with undesirable consequences.
Identification of Immune-Related Breast Cancer Chemotherapy Resistance Genes via Bioinformatics Approaches
Authors: Du Yabing , Han Yikai , Wang Xin , Wang Huanrong , Qu Yanhong , Guo Kaiyuan , Ma Wang , Fu Lijun
Published: March 2022

Chemotherapy resistance in breast cancer is an important factor affecting the prognosis of breast cancer patients. We computationally analyzed the differences in gene expression before and after chemotherapy in breast cancer patients, drug-sensitive groups, and drug-resistant groups. Through functional enrichment analysis, immune microenvironment analysis, and other computational analysis methods, we identified PRC1, GGTLC1, and IRS1 as genes that may mediate breast cancer chemoresistance through the immune pathway. After validation of certain other clinical datasets and in vitro cellular assays, we found that the above three genes influenced drug resistance in breast cancer patients and were closely related to the tumor immune microenvironment. Our finding that chemoresistance in breast cancer could be influenced by the mediation of tumor immunity expanded our knowledge of how to address this problem and could guide future research involving chemoresistance.
Development and Validation of a Novel Tool for the Prediction of Clopidogrel Response in Chinese Acute Coronary Syndrome Patients: The GeneFA Score
Authors: Wu Hongyi , Li Xiaoye , Qian Juying , Zhao Xin , Yao Yao , Lv Qianzhou , Ge Junbo
Published: March 2022

Aim: Growing evidence indicated that CYP2C19 genotypes could only explain a fraction of the pharmacodynamic response to clopidogrel, while a number of clinical factors also have contributing roles. Our objective was to develop a new risk score to improve prognostication of ischemic events in Chinese patients treated with clopidogrel.

Methods: A new risk score was developed and internally validated in 445 patients with acute coronary syndrome (ACS) undergoing coronary stenting. The final score was named the GeneFA score based on the inclusion of CYP2C19 genotype, fibrinogen, and age. External validation of the GeneFA score and comparison with the ABCD-GENE score were performed in an independent ACS cohort.

Results: Based on the observed frequencies of high platelet reactivity (HRPR) in relation to the GeneFA risk score, a relatively higher clinical HRPR was observed in the upper quintile with a representative score of 3 (52.90%) and 4 (59.10%), whereas it was found less frequently in groups with scores 0 (6.70%), 1 (15.10%), and 2 (16.70%). Participants with a GeneFA score >2 had an increased risk of HRPR (54.3 vs. 14.7%, p < 0.001) and ischemic recurrence (20.7 vs. 5.4%, p < 0.001). The GeneFA score exhibited a better prediction for high HRPR patients as compared to the ABCD-GENE score (p < 0.001). In the validation population, GeneFA illustrated a similarly high prognostic value for HRPR incidence (C-statistic: 0.855 for GeneFA and 0.843 for ABCD-GENE) and ischemic recurrence (C-statistic: 0.726 for GeneFA and 0.724 for ABCD-GENE) on clopidogrel as compared to ABCD-GENE.

Conclusion: The GeneFA risk score had a moderate predictive ability for HRPR on clopidogrel for CAD patients in Chinese populations. The predictive value of the GeneFA score was consistent with the ABCD-GENE score for HRPR identification.
The Plant Interspecific Association in the Revegetated Alpine Grasslands Determines the Productivity Stability of Plant Community Across Restoration Time on Qinghai–Tibetan Plateau
Authors: Wu Shengnan , Wen Lu , Dong Shikui , Gao Xiaoxia , Xu Yudan , Li Shuai , Dong Quanming , Wessell Kelly
Published: March 2022

Grassland cultivation is the key measure for restoring “Black Beach,” the extremely degraded alpine meadow in the Three River Headwater Area of the Qinghai–Tibetan Plateau. In this study, we examined the inter-specific relationship in the vegetation community of cultivated grasslands with different restoration times through the network analysis method. The results showed that with the extension of restoration time, the development of cultivated grassland would lead to increasing neutral interactions among the plant species. The proportion of species with positive and negative associations in the community decreased, while the number of species-independent pairs increased significantly. The complexity of plant interspecific association (species network density) had more influence on community stability with the extension of recovery time, which can be used to quantify the characteristics of community structure.
In Situ Analysis of mTORC1/C2 and Metabolism-Related Proteins in Pediatric Osteosarcoma
Authors: Mohás Anna , Krencz Ildikó , Váradi Zsófia , Arató Gabriella , Felkai Luca , Kiss Dorottya Judit , Moldvai Dorottya , Sebestyén Anna , Csóka Monika
Published: March 2022

Activation of the mTOR pathway has been observed in osteosarcoma, however the inhibition of mammalian target of rapamycin (mTOR) complex 1 has had limited results in osteosarcoma treatment. Certain metabolic pathways can be altered by mTOR activation, which can affect survival. Our aim was to characterize the mTOR profile and certain metabolic alterations in pediatric osteosarcoma to determine the interactions between the mTOR pathway and metabolic pathways. We performed immunohistochemistry on 28 samples to analyze the expression of mTOR complexes such as phospho-mTOR (pmTOR), phosphorylated ribosomal S6 (pS6), and rapamycin-insensitive companion of mTOR (rictor). To characterize metabolic pathway markers, we investigated the expression of phosphofructokinase (PFK), lactate dehydrogenase-A (LDHA), β-F1-ATPase (ATPB), glucose-6-phosphate dehydrogenase (G6PDH), glutaminase (GLS), fatty acid synthetase (FASN), and carnitin-O-palmitoyltransferase-1 (CPT1A). In total, 61% of the cases showed low mTOR activity, but higher pmTOR expression was associated with poor histological response to chemotherapy and osteoblastic subtype. Rictor expression was higher in metastatic disease and older age at the time of diagnosis. Our findings suggest the importance of the Warburg-effect, pentose-phosphate pathway, glutamine demand, and fatty-acid beta oxidation in osteosarcoma cells. mTOR activation is linked to several metabolic pathways. We suggest performing a detailed investigation of the mTOR profile before considering mTORC1 inhibitor therapy. Our findings highlight that targeting certain metabolic pathways could be an alternative therapeutic approach.
Characterization of Low-Energy Quasiperiodic Orbits in the Elliptic Restricted 4-Body Problem with Orbital Resonance
Authors: Carletta Stefano , Pontani Mauro , Teofilatto Paolo
Published: March 2022

In this work, we investigate the behavior of low-energy trajectories in the dynamical framework of the spatial elliptic restricted 4-body problem, developed using the Hamiltonian formalism. Introducing canonical transformations, the Hamiltonian function in the neighborhood of the collinear libration point L1 (or L2), can be expressed as a sum of three second order local integrals of motion, which provide a compact topological description of low-energy transits, captures and quasiperiodic libration point orbits, plus higher order terms that represent perturbations. The problem of small denominators is then applied to the order three of the transformed Hamiltonian function, to identify the effects of orbital resonance of the primaries onto quasiperiodic orbits. Stationary solutions for these resonant terms are determined, corresponding to quasiperiodic orbits existing in the presence of orbital resonance. The proposed model is applied to the Jupiter-Europa-Io system, determining quasiperiodic orbits in the surrounding of Jupiter-Europa L1 considering the 2:1 orbital resonance between Europa and Io.
Pot and Ridge Production of Three Highbush Blueberry (Vaccinium corymbosum L.) Cultivars under High Tunnels
Authors: Smrke Tina , Veberic Robert , Hudina Metka , Jakopic Jerneja
Published: March 2022

In recent years, new approaches to intensive blueberry (Vaccinium corymbosum L.) production have become necessary, in terms of protected environments and planting systems. These are designed to avoid numerous production difficulties, such as market saturation, damage from hailstorms, bird attacks, and spring frosts, and specific soil property requirements. Use of high tunnels and planting in a custom substrate (e.g., pots, along ridges) have gained interest among growers in recent years. As in our previous study, we determined the performance of three blueberry cultivars, ‘Duke’, ‘Aurora’, and ‘Brigitta’, when planted in pots and along a ridge under a high tunnel. Substrate water content was maintained at the same level for the pots and the ridge, although the substrate temperature fluctuations were greater for pots. Plant growth in pots was significantly lower for ‘Duke’ and ‘Aurora’ compared to the ridge. Additionally, for ‘Aurora’, the fruit yield was significantly lower for pots (103.4 g/plant), compared to the ridge (315.2 g/plant), although the opposite was seen for ‘Brigitta’ (122.4 vs. 93.5 g/plant, respectively). Individual sugar and organic acid contents mostly coincided with total contents, with lower total sugars for ‘Duke’ and higher total organic acids for ‘Aurora’ and ‘Brigitta’ for pots. For ‘Duke’ and ‘Brigitta’ fruit, the contents of some individual phenolics showed significant differences between treatments for phenolic acids and flavonols. These data show that growth in pots can be a useful planting method for the blueberry cultivars ‘Duke’ and ‘Brigitta’, and high yields and good fruit quality can be attained by following correct technological measures.
Effects of Mechanization and Investments on the Technical Efficiency of Cassava Farms in Cambodia
Authors: Baba Tamon , Nomura Hisako , Srean Pao , Than Tha , Ito Kasumi
Published: March 2022

Cassava is one of the most important cash crops in Cambodia. Agricultural mechanization promotes productivity, but overinvestment may disrupt the balance between inputs and outputs. Depending on the production scale, sometimes hiring equipment is considered better than purchasing it. While we can hypothesize that mechanization and investments might be crucial factors of productivity, technical efficiency analysis for estimating their effects has not yet been conducted. Therefore, this study investigates the impact of mechanization and investments on cassava yield and producers’ technical efficiency in Cambodia using the Cobb-Douglas stochastic frontier production model. For the study, 205 respondents were randomly selected and interviewed in the Battambang and Pailin provinces in northwestern Cambodia in 2017. Our results show that tractor or truck-hire cost was positively significant, and the cassava uprooting machine-hire cost was negatively significant. The average technical efficiency score of 0.62 indicates that cassava producers can increase their level of technical efficiency. Although cassava production in Cambodia is mechanized and investors are investing, it would be more beneficial to producers if they were provided with financial assistance when uprooting the cassava at the harvest time. Appropriate control of input costs can effectively improve cassava yield, following the implementation of the National Policy on Cassava 2020–2025 by the Royal Government of Cambodia.
Environmental Impact Assessment of Sustainable Pig Farm via Management of Nutrient and Co-Product Flows in the Farm
Authors: Venslauskas Kęstutis , Navickas Kęstutis , Rubežius Mantas , Tilvikienė Vita , Supronienė Skaidrė , Doyeni Modupe Olufemi , Barčauskaitė Karolina , Bakšinskaitė Aušra , Bunevičienė Kristina
Published: March 2022

This study evaluates the environmental impact assessment of sustainable pig farm via management of nutrient and co-product flows in the farm. Manure management and biogas production are among the most promising pathways towards fully utilizing organic waste within a circular bioeconomy as the most environmentally friendly solution mitigating gaseous emissions and producing bioenergy and high-quality bio-fertilizers. The concept of farm management includes rearing pig, growing all the feeds needed, and managing the nutrients and co-product flows in the farm. A consequential life cycle assessment (LCA) was performed to examine three scenarios in which all the generated manure is used as fertilizer for barley cultivation and mineral fertilizer is used where necessary (SC1); produced surplus straw is used for thermal energy generation and maize is used for sale, substituting maize biomass in the market (SC2); and all co-products are circulated in a closed system (SC3). The functional unit (FU) was defined as a “farm with 1000 fattening pigs at farm gate”. The analysis showed that heat generation from wheat, barley and legumes straw has a significantly higher positive environmental impact than the use of these cereal straw for biogas production. The partial replacement of mineral fertilizers with digestate has positive environmental effects in terms of abiotic depletion, photochemical oxidation, terrestrial ecotoxicity, freshwater aquatic ecotoxicity, human toxicity, and marine aquatic ecotoxic aspects. The amount of digestate generated on a farm is not sufficient to completely eliminate the use of mineral fertilizers for plant fertilization. The generated pig manure (SC1) and digestate (SC2) is only enough for the fertilization of 8.3% of the total cultivated land of farm applying 22.9 t/ha rate.
Antigestagens Mediate the Expression of Decidualization Markers, Extracellular Matrix Factors and Connexin 43 in Decidualized Dog Uterine Stromal (DUS) Cells
Authors: Kazemian Ali , Tavares Pereira Miguel , Hoffmann Bernd , Kowalewski Mariusz P.
Published: March 2022

Feto-maternal communication in the dog involves the differentiation of stromal cells into decidual cells. As the only placental cells expressing the nuclear progesterone (P4) receptor (PGR), decidual cells play crucial roles in the maintenance and termination of pregnancy. Accordingly, to investigate possible PGR-mediated mechanisms in canine decidual cells, in vitro decidualized dog uterine stromal (DUS) cells were treated with functional PGR-blockers, mifepristone and aglepristone. Effects on decidualization markers, epithelial and mesenchymal factors, and markers of cellular viability were assessed. Decidualization increased the expression of PTGES, PGR, IGF1, and PRLR, along with ECM1, COL4 and CX43, but downregulated IGF2. DUS cells retained their mesenchymal character, and the expression of COL4 indicated the mesenchymal-epithelial transformation. Antigestagen treatment decreased the availability of PTGES, PRLR, IGF1 and PGR. Furthermore, antigestagens decreased the mRNA and protein expression of CX43, and transcriptional levels of ECM1 and COL4. Additionally, antigestagens increased levels of activated-CASP3 (a proapoptotic factor), associated with lowered levels of PCNA (a proliferation marker). These data reveal important aspects of the functional involvement of PGR in canine decidual cells, regarding the expression of decidualization markers and acquisition of epithelial-like characteristics. Some of these mechanisms may be crucial for the maintenance and/or termination of canine pregnancy.
Exploring and Developing the Questions Used to Measure the Human–Dog Bond: New and Existing Themes
Authors: Samet Lauren E. , Vaterlaws-Whiteside Helen , Harvey Naomi D. , Upjohn Melissa M. , Casey Rachel A.
Published: March 2022

Dogs play an important role in many western societies, providing companionship, emotional support, and assistance, as well as other more specialist roles. The literature reveals that many human–animal interaction (HAI) questionnaires exist to measure the human–dog bond (HDB). The first part of this study assessed how far existing questionnaires went in measuring HDB (defined as the unique, dynamic and reciprocated relationship between a person and dog, one in which each member can influence the other’s psychological and physiological state). A systematic literature review revealed that a common limitation in HDB questionnaires was a lack of questions based on the dog’s investment in the bond and, therefore, a failure to measure the two-way characteristic of the HDB. This led to the second part of the study: to identify novel themes relating to dog investment in the HDB from which new tool questions could be developed. This was investigated qualitatively using twelve semi-structured interviews on HDB, undertaken with participants from a variety of dog–guardian relationship types. HDB themes that emerged included ‘adaptation’, ‘understanding of a dog’s preferences, likes, and dislikes’, and ‘affirmation’. Subthemes included ‘boundaries’ and ‘expectations’ (within adaptation), ‘excitement’, ‘proximity’, ‘affection’, and ‘recall’ (within affirmation). The themes that arose provide a foundation from which to build new lines of questioning within HDB tools. Such questioning can better represent a dog’s investment in the HDB and, therefore, help create tools that reflect the reciprocal nature of a bond more accurately.
An Investigation of Ovarian and Adrenal Hormone Activity in Post-Ovulatory Cheetahs (Acinonyx jubatus)
Authors: Koester Diana , Maly Morgan , Putman Sarah , Edwards Katie , Meeks Karen , Crosier Adrienne
Published: March 2022

Cheetahs have been the subject of reproductive study for over 35 years, yet steroid hormone activity remains poorly described after ovulation. Our objective was to examine and compare fecal progestagen (fPM), estrogen (fEM), and glucocorticoid (fGM) metabolite concentrations post-ovulation in pregnant and non-pregnant animals to better understand female physiology (1) during successful pregnancy, (2) surrounding frequent non-pregnant luteal phases, and (3) after artificial insemination (AI) to improve the low success rate. Secondarily, the authors also validated a urinary progestagen metabolite assay, allowing pregnancy detection with minimal sample collection. Fecal samples were collected from 12 females for ≥2 weeks prior to breeding/hormone injection (the PRE period) through 92 days post-breeding/injection. Samples were assessed for hormone concentrations using established enzyme immunoassays. Urine samples were collected for 13 weeks from 6 females after natural breeding or AI. There were no differences among groups in fGM, but in pregnant females, concentrations were higher (p < 0.01) in the last trimester than any other time. For pregnant females that gave birth to singletons, fGM was higher (p = 0.0205), but fEM tended to be lower (p = 0.0626) than those with multi-cub litters. Our results provide insight into the physiological events surrounding natural and artificially stimulated luteal activity in the cheetah.
New Trends in Blockchain Technology
Authors: Lee Heung-No
Published: March 2022

When someone mentions the word blockchain, we find ourselves thinking of words such as decentralization and smart contracts [...]
Linear and Nonlinear Performance Analysis of Hydrodynamic Journal Bearings with Different Geometries
Authors: Viana Carlos Alberto Alves , Alves Diogo Stuani , Machado Tiago Henrique
Published: March 2022

In rotor dynamics, a traditional way of representing the dynamics of hydrodynamic bearings is using stiffness/damping coefficients. It is thus necessary to carry out a linearization of hydrodynamic forces around the shaft’s equilibrium position. However, hydrodynamic bearings have highly nonlinear nature, depending on operating conditions. Therefore, this paper discusses the applicability of these linear/nonlinear approaches using a computational model of the rotating system, where the finite element method is used for rotor modelling and the finite volume method for bearing calculation. The main goal is to investigate the boundaries for linear approximation of the hydrodynamic forces present in lobed hydrodynamic bearings, with the system operating under high loading conditions. Several numerical simulations were performed varying preload parameter and rotating speed. A comparison of the system’s responses, in time domain (shaft orbits) and frequency domain (full spectrum), is made for linear and nonlinear models. Results showed that trilobed bearings are more susceptible to nonlinearities, even in situations of smaller vibration amplitudes, while elliptical bearings are sensitive only under larger vibration amplitudes. These analyses are of great importance for mapping the influence of nonlinearities in different types of lobed hydrodynamic bearings with fixed geometry, varying the preload parameter to verify the influence on the system’s dynamic response. This study is important and serves as the basis for cases of monitoring and fault diagnosis (in the field of structural health monitoring) since it is crucial to distinguish what would be a fault signature or a standard nonlinear effect created by the use of hydrodynamic bearings.
An Operational Image-Based Digital Twin for Large-Scale Structures
Authors: Benzon Hans-Henrik , Chen Xiao , Belcher Lewis , Castro Oscar , Branner Kim , Smit Jesper
Published: March 2022

This study presents a novel methodology to create an operational Digital Twin for large-scale structures based on drone inspection images. The Digital Twin is primarily used as a virtualized representation of the structure, which will be updated according to physical changes during the life cycle of the structure. The methodology is demonstrated on a wind turbine transition piece. A three-dimensional geometry reconstruction of a transition piece as manufactured is created using a large number (>500) of RGB images collected from a drone and/or several LiDAR scans. Comparing the reconstruction to the original design will locate and quantify geometric deviations and production tolerances. An artificial intelligence algorithm is used to detect and classify paint defects/damages from images. The detected and classified paint defects/damages are subsequently digitalized and mapped to the three-dimensional geometric reconstruction of the structure. These developed functionalities allow the Digital Twin of the structure to be updated with manufacturing-induced geometric deviations and paint defects/damages using inspection images at regular time intervals. The key enabling technologies to realize the Digital Twin are presented in this study. The proposed methodology can be used in different industrial sectors, such as the wind energy, oil, and gas industries, aerospace, the marine and transport sector, and other large infrastructures.
Metallic Study of the Invasive Species Cronius ruber—Assessment of Toxic Risk
Authors: Thorne-Bazarra Thabatha , Lozano-Bilbao Enrique , Triay-Portella Raül , Hardisson Arturo , Paz Soraya , Rubio-Armendariz Carmen , Martín Verónica , Gutiérrez Angel J.
Published: March 2022

Three toxic heavy metals (Cd, Pb, and Hg) were analyzed in the newly found invasive species in the Canary Islands, Cronius ruber. Its high growth rate and its widely varied diet are affecting the Canary marine ecosystem. The study was conducted using electrothermal vaporization atomic absorption spectrometry (GF-AAS) and cold-vapor atomic absorption spectrophotometry (CV-AAS). Significant differences were found in terms of the location and sex of the specimens, with the highest concentrations being found in areas with higher tourism activity and in the female specimens. On the other hand, the conclusion of the study is that human consumption of this species does not pose any toxic risk to public health, as the levels obtained in muscle tissue do not exceed the established limits for these metals. Therefore, its consumption and the fishing of this species can stop the proliferation of the same in the Canary coasts and thus not be harmful for the ecosystem.
Predictive Maintenance for Remanufacturing Based on Hybrid-Driven Remaining Useful Life Prediction
Authors: Zhang Ming , Amaitik Nasser , Wang Zezhong , Xu Yuchun , Maisuradze Alexander , Peschl Michael , Tzovaras Dimitrios
Published: March 2022

Remanufacturing is an activity of the circular economy model whose purpose is to keep the high value of products and materials. As opposed to the currently employed linear economic model, remanufacturing targets the extension of products and reduces the unnecessary and wasteful use of resources. Remanufacturing, along with health status monitoring, constitutes a key element for lifetime extension and reuse of large industrial equipment. The major challenge is to determine if a machine is worth remanufacturing and when is the optimal time to perform remanufacturing. The present work proposes a new predictive maintenance framework for the remanufacturing process based on a combination of remaining useful life prediction and condition monitoring methods. A hybrid-driven approach was used to combine the advantages of the knowledge model and historical data. The proposed method has been verified on the realistic run-to-failure rolling bearing degradation dataset. The experimental results combined with visualization analysis have proven the effectiveness of the proposed method.
Genetic and Phenotypic Characteristics of the Salmo trutta Complex in Italy
Authors: D’Agaro Edo , Gibertoni PierPaolo , Marroni Fabio , Messina Maria , Tibaldi Emilio , Esposito Stefano
Published: March 2022

Salmonid fish have become ecological and research models of study in the field of conservation genetics and genomics. Over the last decade, brown trout have received a high level of interest in research and publications. The term Salmo trutta complex is used to indicate the large number of geographic forms present in the species Salmo trutta. In Europe, the S. trutta complex consists (based on mitochondrial DNA control region analysis) of seven major evolutionary lineages: Atlantic (AT), Mediterranean (ME), Adriatic (AD), Danubian (DA), Marmoratus (MA), Duero (DU) and Tigris (TI). In several nations, the difficulty of identifying some lineages derives from their wide phenotypic and geographic plasticity and the presence of mixed lineages (due to introgressive hybridization with domestic AT populations). In Italy, the S. trutta complex populations living in the Tyrrhenian area and on the main islands (Sicily, Sardinia and Corsica) showed high genetic diversity. Currently, on the Italian Red List, the protected (near threatened) populations are the AD and ME lineages. Recent studies based on traditional (mitochondrial and nuclear markers) and NGS (next-generation sequencing) analyses have clarified some genetic differences between the populations of the Tyrrhenian region, Sicily, Sardinia and Corsica. Native populations in Sardinia belong to the AD lineage, while those living in Corsica are mainly characterized by the AD, MA and ME haplotypes. In Sicily, in the area of the Iblei mountains, an AT lineage (North African) exists. According to some authors, the term Salmo macrostigma should only be used for populations in North Africa. The use of genotyping methods based on mtDNA and nuclear markers and the latest generation sequencing techniques can improve the study of populations and evolutionary lineages in areas where there are overlaps and hybridization phenomena.
A Phytochemical Analysis, Microbial Evaluation and Molecular Interaction of Major Compounds of Centaurea bruguieriana Using HPLC-Spectrophotometric Analysis and Molecular Docking
Authors: Noman Omar M. , Herqash Rashed N. , Shahat Abdelaaty A. , Ahamad Syed Rizwan , Mechchate Hamza , Almoqbil Abdulaziz N. , Alqahtani Ali S.
Published: March 2022

Centaurea is one of the most important genera within the family Asteraceae. An investigation of the phytochemical composition of Centaurea bruguieriana using Gas-Chromatography coupled to Mass spectrometry (GC-MS) was performed. Antimicrobial activity was evaluated using the minimum inhibitory concentration method (MIC) and validated by molecular docking for the major compounds of the most active fraction (1,10-di-epi-cubenol and methyl 8-oxooctanoate) of C. bruguieriana against three bacterial receptors (TyrRS, DNA gyrase, and dihydrofolate reductase (DHFR)). Evaluation of antioxidant activity was conducted using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. High-performance liquid chromatography (HPLC) was used to identify and quantify the contents of major compounds from ethyl acetate fraction (luteolin 7-O-glucoside, chlorogenic acid, kaempferol and isorhamnetin). The antimicrobial activity test showed that the chloroform fraction was more active against all microbial strains. The results of the molecular docking of two major compounds from chloroform fraction showed that good affinities were made between 1,10-di-epi-cubenol and the three selected receptors (TyrRs: −6.0 Kcal/mol against −8.2 Kcal/mol obtained with clorobiocin (standard); DNA gyrase: −6.6 Kcal/mol against −9.1 Kcal/mole obtained with clorobiocin; DHFR: −7.4 Kcal/mol against −6.3 Kcal/mol obtained with SCHEMBL2181345 Standard). Antioxidant evaluation showed that the ethyl acetate fraction was the most active fraction in DPPH (IC50 49.4 µg/mL) and ABTS (IC50 52.8 µg/mL) models. HPLC results showed the contents of luteolin 7-O-glucoside (7.4 µg/mg), and chlorogenic acid (3.2 µg/mg). Our study demonstrated that C. bruguierana is a promising source of bioactive compounds.
Structural Stress Characteristics and Joint Deformation of Shield Tunnels Crossing Active Faults
Authors: Li Hanyuan , Li Xinggao , Yang Yi , Liu Yang , Ma Mingzhe
Published: March 2022

Fault dislocation severely threatens the safety of a tunnel structure. Formerly, researchers mainly engaged in the mechanical response of mountain tunnels crossing the fault fracture zone. In contrast, few studies have focused on the structural stress characteristics and joint deformation of the cross-fault shield tunnels. There is an apparent difference between segmental tunnels and mountain tunnels with respect to mechanical properties. In the current study, a three-dimensional numerical model of cross-fault segmental tunnels is established based on the theory of concrete plastic damage constitutive relations using the finite element program ABAQUS. The numerical calculation results are compared with the model test results for validation. Subsequently, the relevant factors affecting the mechanical response of the shield tunnel crossing the active fault are analyzed. The results illustrate that when normal fault dislocation occurs, the shield tunnel structure is initially damaged appearing in the circumferential joints, which is prone to large tension deformation. Otherwise, when reverse faulting occurs by the same displacement, the shield tunnel structure is initially damaged at the arch haunch of the segments, and the deformation of the longitudinal joints is relatively slight. Under the same fault displacement, the bearing capacity of the segmental lining subjected to the reverse fault dislocation is more significant than that of the normal fault dislocation. Both the soil elastic modulus and the vertical distance between the top of the fault and the tunnel exert a considerable impact on the structural damage of the segmental tunnels, bolt stress, and joint deformation. The fault dip angle does not affect the mechanical characteristics of the shield tunnel structure when subjected to normal fault displacement. In reverse faulting cases, with the increase of the fault dip angle, the tunnel structural failure mode transforms from the transverse compression failure of the segments to the shear failure of the circumferential joints.
Modeling and Analysis of FBV Movements for Automotive Driveshafts in the PPR Region
Authors: Bugaru Mihai , Vasile Ovidiu
Published: March 2022

This research’s goal is to model and analyze the forced bending vibrating (FBV) movements for the elements of an automotive driveshaft using a perturbation technique, the asymptotic method approach (AMA), in the region of principal parametric resonance (PPR). The PPR region was chosen because the principal parametric resonance region is one of the essential resonance regions. The model of FBV movements for the automotive driveshaft (AD) considers the aspects of the following phenomena: geometric nonuniformity of the AD elements and shock excitation due to the road. To overcome the equations for the FBV movements of the AD elements, all inertia characteristics were reduced to the longitudinal ax of the midshaft using the variation of the geometric moments of inertia with the concurrent axis and Stener’s theorem. The midshaft of the AD was considered a Timoshenko simply supported beam with a concentrated mass at both ends and springs and dampers for linear and rotational movements at both ends. To determine the equations describing the FBV movements of the AD elements, Hamilton’s principle was used. After establishing the equations of motion for each AD element coupled with the specific boundary conditions, the amplitude and the phase angle were computed for stationary and nonstationary motion in the PPR region using the first order of the AMA, and the dynamic instability frontiers were determined based on the same equations. The dynamic behavior of the AD was investigated concerning the variation of the damping ratio and the variation of the parametric excitation coefficient. The AMA coupled with the model of FBV movements for the AD exhibits the future research directions for analyzing FBV movements for the AD in the regions of superharmonic resonances, subharmonic resonances, combination resonances, internal resonances, and simultaneous resonances. Additionally, the AMA can predict the endurance of the AD and design control of car damping systems.
Between Stirling and Olivetti: Ted Cullinan’s Workplaces Design in the UK
Authors: Spada Marco
Published: March 2022

Ted Cullinan’s (1931–2019) work for Olivetti is complex and fascinating: his mixed-function buildings in Belfast, Dundee, Carlisle and Derby are unique and astonishing artefacts, also if almost unknown to the broader architecture audience. The purpose of this article is to reassemble the phases of this brief but extremely incisive collaboration between Cullinan, James Stirling and the Italian company. From his first Olivetti project, shared with “Big Jim” Stirling in Haslemere—a refurbishment of an Edwardian pre-existence converted into a residence for students and technicians—to the design for Dundee, Carlisle, Belfast and Derby, the impact of Cullinan’s pre-sustainable ideas is palpable. We find these ideas in the elegance of the relationship between building and landscape, in the social agenda, but also in the representativeness of the iconic roofs and in the materials. His work exhibits an architectural versatility that has allowed the buildings to keep intact their essential characteristics, despite their subsequent destinies. Re-reading Cullinan in relation to Olivetti’s buildings, therefore, is two-fold: on the one hand, to reconsider the English architect among the ‘creators’ of the Olivetti image, and on the other to underline how Cullinan was a fundamental interpreter of the ideas of unity, between architecture and industrial design, in a unique phase of the British technological history of the 1970s.
A Boolean Model of the Proliferative Role of the lncRNA XIST in Non-Small Cell Lung Cancer Cells
Authors: Gupta Shantanu , Silveira Daner A. , Hashimoto Ronaldo F. , Mombach Jose Carlos M.
Published: March 2022

The long non-coding RNA X inactivate-specific transcript (lncRNA XIST) has been verified as an oncogenic gene in non-small cell lung cancer (NSCLC) whose regulatory role is largely unknown. The important tumor suppressors, microRNAs: miR-449a and miR-16 are regulated by lncRNA XIST in NSCLC, these miRNAs share numerous common targets and experimental evidence suggests that they synergistically regulate the cell-fate regulation of NSCLC. LncRNA XIST is known to sponge miR-449a and miR-34a, however, the regulatory network connecting all these non-coding RNAs is still unknown. Here we propose a Boolean regulatory network for the G1/S cell cycle checkpoint in NSCLC contemplating the involvement of these non-coding RNAs. Model verification was conducted by comparison with experimental knowledge from NSCLC showing good agreement. The results suggest that miR-449a regulates miR-16 and p21 activity by targeting HDAC1, c-Myc, and the lncRNA XIST. Furthermore, our circuit perturbation simulations show that five circuits are involved in cell fate determination between senescence and apoptosis. The model thus allows pinpointing the direct cell fate mechanisms of NSCLC. Therefore, our results support that lncRNA XIST is an attractive target of drug development in tumor growth and aggressive proliferation of NSCLC, and promising results can be achieved through tumor suppressor miRNAs.