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Alghanim, Firas, Ibrahim Al-Hurani, Hazem Qattous, Abdullah Al-Refai, Osamah Batiha, Abedalrhman Alkhateeb, and Salama Ikki. "Machine Learning Model for Multiomics Biomarkers Identification for Menopause Status in Breast Cancer." Algorithms 17, no. 1 (December 28, 2023): 13. http://dx.doi.org/10.3390/a17010013.
Повний текст джерелаАнотація:
Identifying menopause-related breast cancer biomarkers is crucial for enhancing diagnosis, prognosis, and personalized treatment at that stage of the patient’s life. In this paper, we present a comprehensive framework for extracting multiomics biomarkers specifically related to breast cancer incidence before and after menopause. Our approach integrates DNA methylation, gene expression, and copy number alteration data using a systematic pipeline encompassing data preprocessing and handling class imbalance, dimensionality reduction, and classification. The framework starts with MutSigCV for data preprocessing and ensuring data quality. The Synthetic Minority Over-sampling Technique (SMOTE) up-sampling technique is applied to address the class imbalance representation. Then, Principal Component Analysis (PCA) transforms the DNA methylation, gene expression, and copy number alteration data into a latent space. The purpose is to discard irrelevant variations and extract relevant information. Finally, a classification model is built based on the transformed multiomics data into a unified representation. The framework contributes to understanding the complex interplay between menopause and breast cancer, thereby revealing more precise diagnostic and therapeutic strategies in the future. The explainable artificial intelligence model Shapley based on the XGBoost regressor showed the power of the selected gene expressions for predicting the menopause status, and the potential biomarkers included RUNX1, PTEN, MAP3K1, and CDH1. The literature confirmed the findings.
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Michael Owenvbiugie Eguagie, Idoko Peter Idoko, Onuh Matthew Ijiga, Lawrence Anebi Enyejo, Francisca Chinonye Okafor, and Chinelo Nwaamaka Onwusi. "Geochemical and Mineralogical Characteristics of Deep Porphyry Systems: Implications for Exploration Using ASTER." International Journal of Scientific Research in Civil Engineering 9, no. 1 (January 4, 2025): 01–21. https://doi.org/10.32628/ijsrce25911.
Повний текст джерелаАнотація:
Porphyry systems are critical sources of economically valuable metals, making their identification and exploration a key focus in mineral resource studies. Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data have emerged as a powerful tool for mapping the geochemical and mineralogical characteristics of these systems, enabling more precise exploration efforts. This review examines the geochemical and mineralogical indicators of deep porphyry systems and evaluates the effectiveness of ASTER in their exploration. It begins by exploring the geological framework and alteration zones typical of porphyry deposits, emphasizing the unique advantages of ASTER in remote sensing applications. The methodology focuses on evaluating case studies where ASTER data were utilized to map alteration minerals and detect geochemical anomalies, alongside techniques for data processing and ground-truth validation. Results reveal that ASTER effectively identifies critical alteration zones and mineralogical features, though challenges remain in distinguishing overlapping mineral signatures in complex terrains. Recommendations include integrating ASTER with complementary geophysical and geochemical methods and advancing data processing techniques to enhance exploration accuracy. This study highlights ASTER’s significant potential in driving efficient and sustainable exploration of deep porphyry systems.
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Hai, Nguyen Ngoc, Nguyen Nguyen Chuong, Nguyen Huu Cam Tu, Anna Kisiala, Xuan Lan Thi Hoang, and Nguyen Phuong Thao. "Role and Regulation of Cytokinins in Plant Response to Drought Stress." Plants 9, no. 4 (March 31, 2020): 422. http://dx.doi.org/10.3390/plants9040422.
Повний текст джерелаАнотація:
Cytokinins (CKs) are key phytohormones that not only regulate plant growth and development but also mediate plant tolerance to drought stress. Recent advances in genome-wide association studies coupled with in planta characterization have opened new avenues to investigate the drought-responsive expression of CK metabolic and signaling genes, as well as their functions in plant adaptation to drought. Under water deficit, CK signaling has evolved as an inter-cellular communication network which is essential to crosstalk with other types of phytohormones and their regulating pathways in mediating plant stress response. In this review, we revise the current understanding of CK involvement in drought stress tolerance. Particularly, a genetic framework for CK signaling and CK crosstalk with abscisic acid (ABA) in the precise monitoring of drought responses is proposed. In addition, the potential of endogenous CK alteration in crops towards developing drought-tolerant crops is also discussed.
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Proudfoot, L., J. R. Kusel, H. V. Smith, and M. W. Kennedy. "External stimuli and intracellular signalling in the modification of the nematode surface during transition to the mammalian host environment." Parasitology 107, no. 5 (December 1993): 559–66. http://dx.doi.org/10.1017/s0031182000068141.
Повний текст джерелаАнотація:
SUMMARYPrevious work has shown that the surface of infective larvae of parasitic nematodes will not bind the fluorescent lipid analogue 5-N(octadecanoyl)aminofluorescein (AF18) until after exposure of the parasite to mammalian tissue-culture conditions. In this study, culture media which are permissive or non-permissive for the acquisition of lipophilicity for AF18 were altered in order to examine possible stimuli involved. This showed that external alkaline pH and high sodium ion concentration were highly stimulatory. The internal signalling pathways which may be involved in the surface alteration were then examined using agents which are known to affect intracellular signalling in mammalian cells. The results indicated that elevation of cGMP levels was stimulatory whereas inhibition of a putative Na+/H+ antiporter or calcium mobilization was inhibitory, and it is argued that high intracellular levels of cAMP may be inhibitory. Whilst the precise effects of the agents used on nematode cells remain to be established, these results provide a framework for the examination of the processes involved in the modification of the nematode surface which takes place immediately after the infection event.
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Shapshay, Stanley M., Zhi Wang, Donald F. Perrault, Elie E. Rebeiz, and Michail M. Pankratov. "“Window” Laryngoplasty: A New Combined Laser Endoscopic and Open Technique for Conservation Surgery." Annals of Otology, Rhinology & Laryngology 103, no. 9 (September 1994): 679–85. http://dx.doi.org/10.1177/000348949410300904.
Повний текст джерелаАнотація:
Endoscopic laser resection of early laryngeal carcinoma is an increasingly used treatment modality; however, the limited exposure achieved and the alteration of vocal function are still major problems. A new surgical procedure, “window” laryngoplasty, has been devised and tested in an in vivo study in 6 canines with 50 days' survival. The right vocal cord was incised endoscopically with the carbon dioxide laser, and the en bloc specimen with adjacent thyroid cartilage was removed through a window approach made in the thyroid cartilage. A sternohyoid muscle flap based superiorly was inserted into the cartilaginous window to reconstruct a pseudocord with coverage of either mucosa or fascia. A diode laser soldering technique was used to secure the mucosal graft in place. Epithelial transplantation can be accomplished externally with precise endoscopic guidance for reliable placement of the pseudocord. The results show that the new technique, a combination of endoscopic and open approaches, may be a better treatment choice than standard vertical partial laryngectomy in selected patients. Advantages of this technique include adequate en bloc resection, including adjacent cartilage for pathologic evaluation, preservation of the integrity of most of the laryngeal framework, avoidance of tracheotomy, and better functional results.
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VOLDMAN, GUSTAVO G., JUAN L. ALONSO, LUIS P. FERNÁNDEZ, ALDO L. BANCHIG, GUILLERMO L. ALBANESI, GLADYS ORTEGA, and RAÚL CARDÓ. "Cambrian–Ordovician conodonts from slump deposits of the Argentine Precordillera: new insights into its passive margin development." Geological Magazine 155, no. 1 (October 18, 2016): 85–97. http://dx.doi.org/10.1017/s0016756816000832.
Повний текст джерелаАнотація:
AbstractThe Los Sombreros Formation represents the western continental margin slope deposits of the Argentine Precordillera, a sub-terrane accreted to Gondwana as part of the Cuyania Terrane in early Palaeozoic times. The age of these gravity-driven deposits is controversial and, therefore, a precise biostratigraphic scheme is essential to reveal the evolution of the continental margin. New conodont samplings along with sedimentological and structural analysis carried out in the Los Sombreros Formation in the La Invernada Range provide clues to its depositional framework. The sedimentary succession is made up of dominantly calciturbidites, carbonate breccias and conglomerates, along with mudstones that represent the pelagic/hemipelagic background sedimentation. It displays hectometric to outcrop-scale slump folds with variable hinge-line orientations and pinch-and-swell structures, evidencing soft-sediment deformation, consistent with a slope to base-of-slope setting. Three limestone samples from this succession include conodonts referable to the pandemicHirsutodontus simplexSubzone of theCordylodus intermediusZone (upper Furongian, Cambrian) and from theMacerodus dianaeZone (upper Tremadocian, Ordovician), implying that a slope connected the shallow-water shelf with a deep-water (oceanic) basin at least since late Cambrian times. The conodont faunas show affinities to coeval assemblages from outer shelf and slope environments around Laurentia yet they are not conclusive to postulate a geographic origin for the Precordillera. The thermal alteration of the conodonts is consistent with sedimentary burial and nappe stacking in this sector of the Precordillera.
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Weber, Remi, Flavio Vasella, Artsiom Klimko, Manuela Silginer, Martine L. M. Lamfers, Luca Regli, Gerald Schwank, and Michael Weller. "EXTH-37. TARGETING THE IDH1R132H MUTATION IN GLIOMAS BY CRISPR-CAS PRECISION BASE EDITING." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii217. http://dx.doi.org/10.1093/neuonc/noac209.835.
Повний текст джерелаАнотація:
Abstract Gliomas are the most frequent malignant primary brain tumors and continue to lack curative therapies. To aid the development of novel therapeutic approaches, a better understanding of glioma-specific molecular patterns is essential. We therefore investigate the role of the canonical point mutation in the isocitrate dehydrogenase 1 gene (IDH1R132H). Its early occurrence in oncogenesis and ubiquitous expression suggests a causative driver function; however, current literature is inconclusive on the impact of IDH1R132H, requiring innovative approaches to further elucidate the functional consequences and therapeutic potential of IDH1R132H. METHODS Clustered, regularly interspaced, short palindromic repeat (CRISPR)-Cas precision base editing systems enable the alteration of a specific base pair without suffering from off-target editing associated with previous, double strand brake-inducing systems and thus making them an ideal tool to revert the point mutation in IDH1R132H gliomas. RESULTS By selecting a CRISPR-Cas precision base editing system, the IDH1R132H site was edited with editing efficiencies of up to 50%. Primary patient derived cell lines and organoids were corrected in their IDH1R132H locus. Phenotypical changes, such as a change in IDH1R132H protein levels, 2-hydroxyglutarate concentration as well as proliferation rates were observed upon the reversal of the point mutation. Furthermore, the precision base editing system was packaged into a dual-AAV-vector split intein system and showed successful in vitro gene editing. In conclusion, this precise genetic intervention provides a methodology to create accurate patient derived models to analyze the impact of IDH1R132H on glioma biology and provides a framework for in vivo gene therapy.
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Adamczyk, Mikołaj, Piotr Parasiewicz, Paolo Vezza, Paweł Prus, and Giovanni De Cesare. "Empirical Validation of MesoHABSIM Models Developed with Different Habitat Suitability Criteria for Bullhead Cottus Gobio L. as an Indicator Species." Water 11, no. 4 (April 8, 2019): 726. http://dx.doi.org/10.3390/w11040726.
Повний текст джерелаАнотація:
Application of instream habitat models such as the Mesohabitat Simulation Model (MesoHABSIM) is becoming increasingly popular. Such models can predict alteration to a river physical habitat caused by hydropower operation or river training. They are a tool for water management planning, especially in terms of requirements of the Water Framework Directive. Therefore, model verification studies, which investigate the accuracy and reliability of the results generated, are essential. An electrofishing survey was conducted in September 2014 on the Stura di Demonte River located in north-western Italy. One hundred and sixteen bullhead—Cottus gobio L.—were captured in 80 pre-exposed area electrofishing (PAE) grids. Observations of bullhead distribution in various habitats were used to validate MesoHABSIM model predictions created with inductive and deductive habitat suitability indices. The inductive statistical models used electrofishing data obtained from multiple mountainous streams, analyzed with logistic regression. The deductive approach was based on conditional habitat suitability criteria (CHSC) derived from expert knowledge and information gathered from the literature about species behaviour and habitat use. The results of model comparison and validation show that although the inductive models are more precise and reflect site- and species-specific characteristics, the CHSC model provides quite similar results. We propose to use inductive models for detailed planning of measures that could potentially impair riverine ecosystems at a local scale, since the CHSC model provides general information about habitat suitability and use of such models is advised in pre-development or generic scale studies. However, the CHSC model can be further calibrated with localized electrofishing data at a lower cost than development of an inductive model.
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Meiliana, Anna, Nurrani Mustika Dewi, and Andi Wijaya. "Mitochondrial Dysfunction in Stem Cell Aging." Indonesian Biomedical Journal 7, no. 1 (April 1, 2015): 15. http://dx.doi.org/10.18585/inabj.v7i1.18.
Повний текст джерелаАнотація:
BACKGROUND: Regardless of the precise underlying molecular mechanisms, the fundamental defining manifestation of aging is an overall decline in the functional capacity of various organs to maintain baseline tissue homeostasis and to respond adequately to physiological needs under stress. There is an increasingly urgent need for a more complete understanding of the molecular pathways and biological processes underlying aging and age-related disorders.CONTENT: Mitochondria constitute the most prominent source of adenosine triphosphate (ATP) and are implicated in multiple anabolic and catabolic circuitries. In addition, mitochondria coordinate cell-wide stress responses and control non-apoptotic cell death routines. The involvement of mitochondria in both vital and lethal processes is crucial for both embryonic and postembryonic development, as well as for the maintenance of adult tissue homeostasis. Age-associated telomere damage, diminution of telomere ‘capping’ function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, ‘stemness’ and metabolism provides a framework for how diverse factors contribute to aging and age-related disorders.SUMMARY: Cellular senescence defined as an irreversible proliferation arrest promotes age-related decline in mammalian tissue homeostasis. The aging of tissue-specific stem cell and progenitor cell compartments is believed to be central to the decline of tissue and organ integrity and function in the elderly. Taken into consideration that the overwhelming majority of intracellular reactive oxygen species (ROS) are of mitochondrial origin, it is reasonable to posit that the elevated ROS production might be caused by alteration in mitochondrial function during senescence. It is likely that mitochondria and stem cells will remain at the forefront of aging research also for the next decade.KEYWORDS: aging, stem cell, mitochondrial biogenesis, mitophagy, senescence, telomeres
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Raimondi, D., A. V. Martynenko, L. Barsi, N. Marchitto, and L. V. Maliarova. "Biofeedback of elderly patients with chronic pain: new nonlinear Heart Rate Variability analysis." Journal of V. N. Karazin Kharkiv National University, Series "Medicine", no. 49 (June 28, 2024): 161–71. http://dx.doi.org/10.26565/2313-6693-2024-49-04.
Повний текст джерелаАнотація:
Background. Chronic pain presents a substantial clinical challenge affecting individuals across all age groups, regardless of whether they are adults or older adults. To underscore the impact of biofeedback in managing chronic pain, we conducted a statistical analysis to explore its short-term effectiveness and factors influencing treatment outcomes. Purpose – to develop the advanced heart rate variability (HRV) methods that reflect a statistically significant relationship between the impact of biofeedback on chronic pain control and HRV indicators that outline changes in the influence of the sympathetic and parasympathetic systems in pain regulation. Materials and Methods. Elderly patients with mean age 76.3 ± 7.5 years suffering from Chronic Pain associated with Chronic Skeletal Illness. Prior to treatment and after a 15-day period, all participants underwent assessment of pain severity. Additionally, each participant underwent a 5-minute EKG recording before and after treatment to evaluate Heart Rate Variability (HRV). Neuro-vegetative cardiovascular modulation was assessed through EKG analysis of HRV before and after treatment. Biofeedback sessions (5 breaths per minute) were conducted twice daily for 5 minutes over the course of 15 days. For the purpose of this research data analysis, we propose a novel Heart Rate Variability (HRV) methodology incorporating robust entropy estimation and fuzzy logic algorithms. The robust entropy estimation algorithm enables precise computation of entropy values from time series data of limited length, while the fuzzy logic algorithm facilitates integration of various HRV metrics (including time domain, frequency domain, and nonlinear methods) into a unified framework. Results. Through the utilization of this proposed methodology, we assess the therapeutic efficacy of biofeedback and the involvement of the neuro-vegetative cardiovascular system in chronic pain. Conclusions. Our preliminary findings reveal a statistically significant reduction in pain severity, as measured by the Visual Analog Scale (VAS), without a statistically significant alteration in neuro-vegetative cardiovascular modulation using conventional analysis techniques. However, the application of the new HRV methodology incorporating robust entropy estimation and fuzzy logic algorithms enables the detection of significant variations.
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Michel, Patrick, Luisa-M. Lara, Bernard Marty, Detlef Koschny, Maria Antonietta Barucci, Andy Cheng, Hermann Bohnhardt, et al. "MarcoPolo-R: Near Earth Asteroid Sample Return Mission candidate as ESA-M3 class mission." Proceedings of the International Astronomical Union 10, H16 (August 2012): 163. http://dx.doi.org/10.1017/s1743921314005183.
Повний текст джерелаАнотація:
AbstractMarcoPolo-R is a sample return mission to a primitive Near-Earth Asteroid (NEA) selected in February 2011 for the Assessment Study Phase at ESA in the framework of ESAfs Cosmic Vision 2 program. MarcoPolo-R is a European-led mission with a proposed NASA contribution. MarcoPolo-R takes advantage of three industrial studies completed as part of the previous Marco Polo mission (see ESA/SRE (2009)3). The aim of the new Assessment Study is to reduce the cost of the mission while maintaining its high science level, on the basis of advanced studies and technologies, as well as optimization of the mission. MarcoPolo-R will rendezvous with a unique kind of target, a primitive binary NEA, scientifically characterize it at multiple scales, and return a unique pristine sample to Earth unaltered by the atmospheric entry process or terrestrial weathering. The baseline target of MarcoPolo-R is the primitive binary NEA (175706) 1996 FG3, which offers a very efficient operational and technical mission profile. A binary target also provides enhanced science return: the choice of this target will allow new investigations to be performed more easily compared to a single object, and also enables investigations of the fascinating geology and geophysics of asteroids that are impossible to obtain from a single object. Precise measurements of the mutual orbit and rotation state of both components can be used to probe higher-level harmonics of the gravitational potential, and therefore the internal structure. A unique opportunity is offered to study the dynamical evolution driven by the YORP/Yarkovsky thermal effects. Possible migration of regolith on the primary from poles to equator allows the increasing maturity of asteroidal regolith with time to be expressed as a latitude-dependent trend, with the most-weathered material at the equator matching what is seen in the secondary. MarcoPolo-R will allow us to study the most primitive materials available to investigate early solar system formation processes. Moreover, MarcoPolo-R will provide a sample from a known target with known geological context. Direct investigation of both the regolith and fresh interior fragments is also impossible by any means other than sample return. The main goal of the MarcoPolo-R mission is to return unaltered NEA material for detailed analysis in ground-based laboratories. The limited sampling provided by meteorites does not offer the most primitive material available in near-Earth space. More primitive material, having experienced less alteration on the asteroid, will be more friable and would not survive atmospheric entry in any discernible amount. Only in the laboratory can instruments with the necessary precision and sensitivity be applied to individual components of the complex mixture of materials that forms an asteroid regolith, to determine their precise chemical and isotopic composition. Such measurements are vital for revealing the evidence of stellar, interstellar medium, pre-solar nebula and parent body processes that are retained in primitive asteroidal material, unaltered by atmospheric entry or terrestrial contamination. It is no surprise therefore that sample return missions are considered a priority by a number of the leading space agencies.
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Edworthy, Judy. "Interval and Contour in Melody Processing." Music Perception 2, no. 3 (1985): 375–88. http://dx.doi.org/10.2307/40285305.
Повний текст джерелаАнотація:
Musician subjects were required to detect interval and contour changes in transposed versions of standard melodies of 3, 5, 7, 9,11,13, and 15 notes. Subjects were significantly better at detecting contour alterations for melodies of up to 11 notes but significantly better at detecting interval alterations in the 15-note melodies. Serial position effects for 5-, 7-, and 9-note melodies showed contour to be immediately precise after transposition, whereas the ability to detect interval alterations improved as the melodies progressed. These results suggest that, on transposition, contour information is immediately precise but is lost as melody length increases. Interval information is initially less precise but is more resistant to forgetting in longer melodies. The implication of this is that contour can be encoded independently of tonal context, whereas interval information becomes more precise as a tonal framework is established. Some musical implications of the finding are discussed.
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Molitoris, B. A. "Putting the actin cytoskeleton into perspective: pathophysiology of ischemic alterations." American Journal of Physiology-Renal Physiology 272, no. 4 (April 1, 1997): F430—F433. http://dx.doi.org/10.1152/ajprenal.1997.272.4.f430.
Повний текст джерелаАнотація:
The actin cytoskeleton plays an ever-increasingly understood role in mediating a myriad of processes necessary for cellular structure and function. New and exciting information regarding the dynamic aspects of the actin cytoskeleton and its intracellular regulation are unfolding at a rapid rate. Actin cytoskeletal-surface membrane interactions mediating such diverse cellular events as cell polarity, endocytosis, exocytosis, cell division, cellular migration, cell adhesion, signal transduction, and ion channel activity are part of an ever-growing list of cellular processes dependent on precise actin polarization and regulation of assembly and disassembly. The purpose of this review is to highlight recent advances in the understanding of actin cytoskeleton-mediated cellular processes, to provide a framework that interrelates the complex protein-protein interactions necessary for localization, regulation, and mediation of these essential cellular functions, and to outline the role of actin effector proteins in the pathophysiology of ischemic cell injury.
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Jagannathan, Jayaganesh, and M. Y. Mohamed Parvees. "Cognitive Intelligence for Interrogation and Inflation of Information Security: A Survey." Journal of Applied Research and Technology 20, no. 5 (October 31, 2022): 570–75. http://dx.doi.org/10.22201/icat.24486736e.2022.20.5.1310.
Повний текст джерелаАнотація:
Information security is the set of forms that secure data faraway from illegal connection, revelation, duplication, alteration. As of late, increasingly legitimate frameworks such as resourceful inter and intra urban city, remote sensor systems, authentication digital signature frameworks, and superintendence, have recently needed data security affirmations. Hence, over the past researches numerous diverse strategies focused on cognitive intelligence are created for data security. In any case, there are not complete reviews which recapitulate strategies. In this way, this document surveyed on cognitive intelligence move toward presented on publications and symposiums for data security within most recent years. This article gives a precise review to audit various cognitive intelligence access and applications of data security. In additionally, deliberate the threat of cognitive intelligence access and applications for data security is conferred.
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Khan, Asma, Sharaf J. Malebary, L. Minh Dang, Faisal Binzagr, Hyoung-Kyu Song, and Hyeonjoon Moon. "AI-Enabled Crop Management Framework for Pest Detection Using Visual Sensor Data." Plants 13, no. 5 (February 27, 2024): 653. http://dx.doi.org/10.3390/plants13050653.
Повний текст джерелаАнотація:
Our research focuses on addressing the challenge of crop diseases and pest infestations in agriculture by utilizing UAV technology for improved crop monitoring through unmanned aerial vehicles (UAVs) and enhancing the detection and classification of agricultural pests. Traditional approaches often require arduous manual feature extraction or computationally demanding deep learning (DL) techniques. To address this, we introduce an optimized model tailored specifically for UAV-based applications. Our alterations to the YOLOv5s model, which include advanced attention modules, expanded cross-stage partial network (CSP) modules, and refined multiscale feature extraction mechanisms, enable precise pest detection and classification. Inspired by the efficiency and versatility of UAVs, our study strives to revolutionize pest management in sustainable agriculture while also detecting and preventing crop diseases. We conducted rigorous testing on a medium-scale dataset, identifying five agricultural pests, namely ants, grasshoppers, palm weevils, shield bugs, and wasps. Our comprehensive experimental analysis showcases superior performance compared to various YOLOv5 model versions. The proposed model obtained higher performance, with an average precision of 96.0%, an average recall of 93.0%, and a mean average precision (mAP) of 95.0%. Furthermore, the inherent capabilities of UAVs, combined with the YOLOv5s model tested here, could offer a reliable solution for real-time pest detection, demonstrating significant potential to optimize and improve agricultural production within a drone-centric ecosystem.
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Rajasekar, Poojitha, Jamie Patel, and Rachel L. Clifford. "DNA Methylation of Fibroblast Phenotypes and Contributions to Lung Fibrosis." Cells 10, no. 8 (August 3, 2021): 1977. http://dx.doi.org/10.3390/cells10081977.
Повний текст джерелаАнотація:
Fibroblasts are an integral part of connective tissue and play a crucial role in developing and modulating the structural framework of tissues by acting as the primary source of extracellular matrix (ECM). A precise definition of the fibroblast remains elusive. Lung fibroblasts orchestrate the assembly and turnover of ECM to facilitate gas exchange alongside performing immune functions including the secretion of bioactive molecules and antigen presentation. DNA methylation is the covalent attachment of a methyl group to primarily cytosines within DNA. DNA methylation contributes to diverse cellular phenotypes from the same underlying genetic sequence, with DNA methylation profiles providing a memory of cellular origin. The lung fibroblast population is increasingly viewed as heterogeneous with between 6 and 11 mesenchymal populations identified across health and lung disease to date. DNA methylation has been associated with different lung fibroblast populations in health and with alterations in lung disease, but to varying extents. In this review, we will discuss lung fibroblast heterogeneity and the evidence for a contribution from DNA methylation to defining cell populations and alterations in disease.
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Rajaram, J., M. Nalini, and N. Vadivelan. "Machine Learning Algorithm Based Bandwidth Prediction for Internet Usage." Journal of Computational and Theoretical Nanoscience 17, no. 8 (August 1, 2020): 3749–53. http://dx.doi.org/10.1166/jctn.2020.9314.
Повний текст джерелаАнотація:
The applicability of framework structure and affiliation arranging recognize a basic activity in the bandwidth prediction. The procedure for predicting the framework use is to see the basic transmission limit with respect to future periods. This prediction helps with utilizing the techniques workplaces in the saint way. Thinking about the fundamental cost of bandwidth, at top hours of a framework traffic we can follow an amazing sort of plan to purchase. In this paper, the past use data of FWDR organize centers is at risk to univariate direct time plan ARIMA model after precise change is used to calculate necessary bandwidth limit concerning future needs. The anticipated data is veered from the obvious data gained from a for all intents and purposes indistinguishable framework and the foreseen data has been viewed as inside ten percent MAPE. This design reduction the MAPE by eleven point seventy-one percentage and fifteen point forty-two percent of self-rulingly when stood separated from the non-able changed ARIMA model at ninety-nine percent CI. The outcome show that the suitably changed ARIMA design has improved show when meandered from non-intentionally changed ARIMA model. Increasingly significant dataset can be passed on with season alterations and thought of expanded length groupings, for dynamically unequivocal and longer term needs.
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Razaghi, Zhina, and Guo-zhen Zhu. "Microscopic Characteristics of Kinking Phenomenon in Vertically Free-Standing Nanowires." Crystals 13, no. 10 (October 3, 2023): 1459. http://dx.doi.org/10.3390/cryst13101459.
Повний текст джерелаАнотація:
Vertically free-standing nanowires, synthesized through vapor-based growth, can undergo changes in their growth directions known as kinking. These alterations can significantly influence the physical and chemical properties of nanowires, thereby expanding their potential applications. The occurrence of kinks is commonly associated with variations in vapor, temperature, seed, and/or their combinations. However, the interplay among different growth factors complicates the identification of the dominating factor and, consequently, limits precise control over nanowire morphology. Theoretical models, incorporating factors like supersaturation, wetting angle, nanowire size, and surface/interface energies tied to growth conditions, have been developed to describe and predict kinking during nanowire growth. While a few pivotal parameters, such as surface/interface energies and wetting angles, can be subtly adjusted through minor alterations in growth conditions, accurately predicting the occurrence of kinks remains a practical challenge. Conversely, in the present review, we attempted to elucidate connections between microscopic aspects, such as changes in composition and the formation of defects, and the nucleation and progression of kinks. This effort aims to construct a predictive framework that enhances our understanding of the tendencies in nanowire growth.
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Gao, Ai, Jiaqi Lv, and Yanwei Su. "The Inflammatory Mechanism of Parkinson’s Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut–Brain Axis." Brain Sciences 15, no. 2 (February 6, 2025): 159. https://doi.org/10.3390/brainsci15020159.
Повний текст джерелаАнотація:
Parkinson’s disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson’s disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson’s disease, emphasizing alterations in gut microbiota and their metabolites that influence the disease’s progression through the bidirectional transmission of inflammatory signals along the gut–brain axis. Building on this mechanistic framework, this article further discusses research methodologies and treatment strategies focused on gut microbiota metabolites, including metabolomics detection techniques, animal model investigations, and therapeutic approaches such as dietary interventions, probiotic treatments, and fecal transplantation. Ultimately, this article aims to elucidate the relationship between gut microbiota metabolites and the inflammatory mechanisms underlying Parkinson’s disease, thereby paving the way for novel avenues in the research and treatment of this condition.
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Buonsanti, Michele, Giovanni Leonardi, Giuseppe Megali, and Francesco Scoppelliti. "Rotating Electromagnetic System for Railway Track Crack Detection." Advanced Materials Research 875-877 (February 2014): 401–5. http://dx.doi.org/10.4028/www.scientific.net/amr.875-877.401.
Повний текст джерелаАнотація:
The aim of this paper is to provide an alternative methodology, high reliability, in order to monitor, exploiting non-invasive techniques, railway track. In this particular case study, the presence of structural defects is assessed through an innovative system. The proposed approach provides the use of rotating magnetic field. Within this framework, the Eddy Current Techniques (ECTs) have greatly increased their importance for their capacity to detect the magnetic field variations caused by the presence of material alterations. Whilst the researches in this field propose various solutions to the detection of flaws (in surface and subsurface), a still open problem concerns the difficult detection of defects due to the geometrical complexity of the structure and the particular orientations of the crack. Particularly, this contribution proposes an approach based on Finite Element (Finite Element Method, FEM) for the modeling of railway tracks, in order to obtain a rapid and precise assessment about their integrity.
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Fattore, Carmen, Sara Porcari, Arcangelo Priore, and Vito Domenico Porcari. "Non-Invasive Techniques for Monitoring Cultural Heritage: Change Detection in Dense Point Clouds at the San Pietro Barisano Bell Tower in Matera, Italy." Heritage 8, no. 1 (December 30, 2024): 14. https://doi.org/10.3390/heritage8010014.
Повний текст джерелаАнотація:
This study examines change detection techniques in dense point clouds for the purpose of cultural heritage preservation, with a particular focus on the San Pietro Barisano Bell Tower in Matera, Italy. Dense point clouds, obtained via laser scanning, offer detailed 3D representations of heritage structures, facilitating the precise monitoring of changes over time. The investigation uses a variety of change detection algorithms, including the Iterative Closest Point (ICP) algorithm, which is renowned for its robust registration capabilities in aligning point clouds with high accuracy. The combination of ICP with deviation analysis and feature-based methods allows for the effective identification of alterations, including deformations, material loss, and surface degradation. This methodology establishes a comprehensive framework for the monitoring of cultural heritage, thereby enabling timely and targeted preservation efforts. The results emphasise the substantial contribution of dense point cloud analysis to the enhancement of heritage management and the safeguarding of vulnerable architectural sites.
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Peng, Xuefeng, Rong Zhao, and Kai Deng. "A Comprehensive Numerical Model for Reservoir-Induced Earthquake Risk Assessment." Entropy 25, no. 10 (September 26, 2023): 1383. http://dx.doi.org/10.3390/e25101383.
Повний текст джерелаАнотація:
The assessment of seismic risk and the prevention of earthquake occurrences during reservoir operation present significant challenges in terms of accurate determination. This study aims to address this issue by developing a numerical model. The primary objective is to estimate the vulnerability of different fault types to reservoir impoundment. This model integrates essential parameters such as fault dip and the relative orientation between the reservoir and potential earthquakes, and it is structured within a risk framework using polar coordinates. Through comprehensive computations, we evaluate the alterations in elastic stress and fluid pore pressure resulting from water impoundment. This is achieved by employing a fully coupled two-dimensional poroelastic approach. Furthermore, our model incorporates relevant seismic data to enhance its accuracy. The findings of our study underscore that the critical factor lies in the fault’s precise positioning with respect to the reservoir. The risk associated with a fault is contingent upon both its location and its orientation, emphasizing the importance of these factors in determining hazardous zones.
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Li, Yunhe, and Boyang Zhang. "Cancer Research Using Crispr/Cas9 Gene Editing Technology." Highlights in Science, Engineering and Technology 45 (April 18, 2023): 291–95. http://dx.doi.org/10.54097/hset.v45i.7443.
Повний текст джерелаАнотація:
Gene editing technology has completely transformed the life sciences and medical treatment, because it makes precise and stable genetic alterations to genomic sequences possible. Among gene editing technologies, CRISPR system is now the most employed one. CRISPR technology is currently often used in the medical field including cancer study as well as genome editing in a number of animals. Besides, the CRISPR system has been widely used in agriculture, industry and other fields, such as crop breeding, industrial microbial design, viral nucleic acid detection, etc. In the framework of people’s knowledge of cancer research and genome editing technology, this paper focuses on the adhibition of CRISPR/Cas9 in cancer modeling, high throughput genetic analysis of tumor cell metastasis-related genes, as well as cancer treatment. It indicates that CRISPR/Cas9 techniques can be a promising tool in cancer diagnostics and therapeutics. Although CRISPR / Cas9 technology has limitations such as being off-target, this technology undoubtedly has great potential in cancer or other diseases in the future.
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Aliyev, Tofiq, and Duyğu Eyvazova. "Genetic Engineering and Its Ethical Implications: A Bioethical Perspective." Luminis Applied Science and Engineering 2, no. 1 (March 13, 2025): 57–64. https://doi.org/10.69760/lumin.20250001010.
Повний текст джерелаАнотація:
Genetic engineering has revolutionized the fields of medicine, agriculture, and biotechnology, offering unprecedented control over DNA modification. The development of CRISPR-Cas9 and other gene-editing tools has enabled precise genetic alterations, raising both scientific opportunities and ethical dilemmas. This paper explores the methodologies of germline and somatic gene editing, the applications of gene drives in conservation, and the corporate influence on genetically modified organisms (GMOs). Ethical concerns regarding human genetic modification, ecological risks, and economic inequalities are critically examined. Additionally, the study highlights bioethical principles, regulatory frameworks, and global governance approaches aimed at ensuring the responsible use of genetic engineering. The findings emphasize the need for adaptive regulations, interdisciplinary collaboration, and public engagement to balance scientific progress with ethical responsibility. While genetic engineering holds immense potential, its future depends on the establishment of equitable, ethical, and sustainable policies that align with human rights and ecological integrity.
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Bu, Xuan, Miao Cao, Xiaoqi Huang, and Yong He. "The structural connectome in ADHD." Psychoradiology 1, no. 4 (December 2021): 257–71. http://dx.doi.org/10.1093/psyrad/kkab021.
Повний текст джерелаАнотація:
Abstract Attention-deficit/hyperactivity disorder (ADHD) has been conceptualized as a brain dysconnectivity disorder. In the past decade, noninvasive diffusion magnetic resonance imaging (dMRI) studies have demonstrated that individuals with ADHD have alterations in the white matter structural connectome, and that these alterations are associated with core symptoms and cognitive deficits in patients. This review aims to summarize recent dMRI-based structural connectome studies in ADHD from voxel-, tractography-, and network-based perspectives. Voxel- and tractography-based studies have demonstrated disrupted microstructural properties predominantly located in the frontostriatal tracts, the corpus callosum, the corticospinal tracts, and the cingulum bundle in patients with ADHD. Network-based studies have suggested abnormal global and local efficiency as well as nodal properties in the prefrontal and parietal regions in the ADHD structural connectomes. The altered structural connectomes in those with ADHD provide significant signatures for prediction of symptoms and diagnostic classification. These studies suggest that abnormalities in the structural connectome may be one of the neural underpinnings of ADHD psychopathology and show potential for establishing imaging biomarkers in clinical evaluation. However, given that there are inconsistent findings across studies due to sample heterogeneity and analysis method variations, these ADHD-related white matter alterations are still far from informing clinical practice. Future studies with larger and more homogeneous samples are needed to validate the consistency of current results; advanced dMRI techniques can help to generate much more precise estimation of white matter pathways and assure specific fiber configurations; and finally, dimensional analysis frameworks can deepen our understanding of the neurobiology underlying ADHD.
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Ponssa, Maria Laura, and Virginia Abdala. "Phenotypical expression of reduced mobility during limb ontogeny in frogs: the knee-joint case." PeerJ 4 (February 18, 2016): e1730. http://dx.doi.org/10.7717/peerj.1730.
Повний текст джерелаАнотація:
Movement is one of the most important epigenetic factors for normal development of the musculoskeletal system, particularly during genesis and joint development. Studies regarding alterations to embryonic mobility, performed on anurans, chickens and mammals, report important phenotypical similarities as a result of the reduction or absence of this stimulus. The precise stage of development at which the stimulus modification generates phenotypic modifications however, is yet to be determined. In this work we explore whether the developmental effects of abnormal mobility can appear at any time during development or whether they begin to express themselves in particular phases of tadpole ontogeny. We conducted five experiments that showed that morphological abnormalities are not visible until Stages 40–42. Morphology in earlier stages remains normal, probably due to the fact that the bones/muscles/tendons have not yet developed and therefore are not affected by immobilization. These results suggest the existence of a specific period of phenotypical expression in which normal limb movement is necessary for the correct development of the joint tissue framework.
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Atuahene, Samuel, Yukun Bao, Yao Ziggah, Patricia Gyan, and Feng Li. "Short-Term Electric Power Forecasting Using Dual-Stage Hierarchical Wavelet- Particle Swarm Optimization- Adaptive Neuro-Fuzzy Inference System PSO-ANFIS Approach Based On Climate Change." Energies 11, no. 10 (October 19, 2018): 2822. http://dx.doi.org/10.3390/en11102822.
Повний текст джерелаАнотація:
Analyzing electrical power generation for a wind turbine has associated inaccuracies due to fluctuations in environmental factors, mechanical alterations of wind turbines, and natural disaster. Thus, development of a highly reliable prediction model based on climatic conditions is crucial in forecasting electrical power for proper management of energy demand and supply. This is essential because early forecasting systems will enable an energy supplier to schedule and manage resources efficiently. In this research, we have put forward a novel electrical power prediction model using wavelet and particle swarm optimization based dual-stage adaptive neuro-fuzzy inference system (dual-stage Wavelet-PSO-ANFIS) for precise estimation of electrical power generation based on climatic factors. The first stage is used to project wind speed based on meteorological data available, while the second stage took the output wind speed prediction to predict electrical power based on actual supervisory control and data acquisition (SCADA). Furthermore, influence of data dependence on the forecasting accuracy for both stages is analyzed using a subset of data as input to predict the wind power which was also compared with other existing electrical power forecasting techniques. This paper defines the basic framework and the performance evaluation of a dual-stage Wavelet-PSO-ANFIS based electrical power forecasting system using a practical implementation.
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Yang, Yiqi, та Guobao Huang. "Biomechanical and inflammatory pathways of IL-1β in ARDS: Insights from extensive burn injuries". Molecular & Cellular Biomechanics 22, № 4 (10 березня 2025): 1496. https://doi.org/10.62617/mcb1496.
Повний текст джерелаАнотація:
Acute Respiratory Distress Syndrome (ARDS) is a severe complication often seen in patients with extensive burns, driven by systemic inflammation mediated by interleukin-1β (IL-1β). Understanding the biomechanical and inflammatory pathways, as well as long-term complications, is critical for improving therapeutic interventions. However, existing approaches often fail to comprehensively address the interplay between IL-1β and the systemic inflammatory response, particularly in the context of biomechanical stress on lung tissue, leading to limited efficacy in mitigating ARDS-related morbidity and mortality. Furthermore, these methods lack precise strategies to predict and monitor disease progression in burn patients, especially in terms of biomechanical alterations in pulmonary function. The proposed framework emphasizes ARDS as the focal point for addressing systemic inflammation in burn patients by targeting IL-1β-mediated inflammatory pathways (IL-1β-MIP) and their biomechanical consequences. The method integrates advanced biomarker analysis and molecular-level therapeutic interventions focusing on IL-1β inhibition to assess the impact of inflammation on lung compliance and tissue stiffness. The proposed approach utilizes a combination of precision medicine, including cytokine-modulating therapies, alongside early diagnostic tools such as IL-1β serum level monitoring. This framework aims to alleviate acute symptoms and mitigate the risk of long-term complications such as pulmonary fibrosis and immune dysregulation, which are often associated with altered tissue mechanics. The findings demonstrate that targeted IL-1β modulation significantly reduces ARDS severity, improving survival rates and reducing long-term complications. IL-1β-MIP highlights the potential of personalized anti-inflammatory therapies in transforming ARDS management in patients with extensive burns, providing a foundation for future clinical advancements that integrate biomechanical insights into therapeutic strategies.
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Sabatier, Jean-Marc, and Farzan Amini. "From Endogenous Quasi-Pathogens to Endogenous Smart Medicine: Understanding the Cellular Mechanisms and Implications of Benign and Malignant Cell Dynamics." Biophysica 4, no. 3 (September 20, 2024): 453–65. http://dx.doi.org/10.3390/biophysica4030029.
Повний текст джерелаАнотація:
This study investigates the formation and impact of Endogenous Quasi-Pathogens (EQPs) within cellular environments, focusing on the role of Endogenous Smart Medicine (ESM) as a therapeutic intervention. This work elucidates how induced vibrations facilitate new molecular and atomic connections between adjacent cells, leading to endobiotic bond formation and significantly altered DNA behavior. These vibrations, which dominate cellular processes, induce both temporary and permanent changes in cellular dynamics. The resulting increase in extracellular impedance triggers the emergence of new EQP sources, potentially initiating divergent pathological cycles. Cells experiencing moderate impedance changes are classified as benign, while those with substantial alterations are considered malignant. This study highlights the medical diagnostic implications of EQPs and positions ESM as a precise method for modulating cellular impedance, reducing the effects of EQPs, and potentially treating diseases where disruptions in cellular dynamics and stiffness are critical. Additionally, the integration of ChronoBit Storage (CBS) within ESM introduces a novel energy management mechanism, enhancing therapeutic precision by synchronizing energy distribution with cellular needs. The ChronoVital Index (CVI), a temporal model for assessing time dynamics across biological systems from individual cells to whole organs further refines this approach. By advancing the CVI and CBS, this research paves the way for more sophisticated therapeutic strategies, offering promising applications in the fields of disease management and cellular restoration within the framework of Endogenous Smart Medicine.
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Han, Zhaoxu. "Optimizing Parameters and Applications of Femtosecond Laser Technology in Fiber Bragg Grating Manufacture." Highlights in Science, Engineering and Technology 92 (April 10, 2024): 387–96. http://dx.doi.org/10.54097/1pc4cw24.
Повний текст джерелаАнотація:
Fiber Bragg Grating (FBG) sensors have garnered extensive attention for their pivotal role in diverse domains, including strain, pressure, hydroacoustics, and temperature monitoring, especially within the ambit of the Internet of Things (IoT). The femtosecond laser point-by-point fabrication methodology stands out in this context, primarily for its flexibility in altering FBG periods through precise control of the fiber’s movement velocity. This adaptability facilitates the creation of FBGs with varied periodicities, significantly broadening their application spectrum. A notable aspect of FBG sensors is their sensitivity to temperature variations, which manifest as changes in both the grating pitch and the refractive index of the FBG. These alterations consequently induce shifts in the FBG’s reflection and transmission spectra. Specifically, temperature fluctuations lead to a discernible drift in the central wavelength of the light reflected by the Bragg grating. This wavelength drift is linearly proportional to the temperature change, rendering it a reliable metric for assessing both the magnitude and rate of temperature variations. Experimental framework was centered around the femtosecond laser point-by-point fabrication technique for FBG creation. Within this setup, we delved into four critical factors influencing the spectral quality of the FBGs: grating length, periodicity, laser energy, and grating position. By meticulously adjusting these parameters, we aimed to optimize the performance and applicability of FBG sensors in real-world IoT scenarios.
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Al-Shaeli, Sattar J. J., Baidaa H. R. Al-Mahna, Ali M. Ethaeb, and Hasanain A. J. Gharban. "Review Article: Anatomical and Physiological Development of Reproductive System in Female Murine." Journal of Medical and Health Sciences (JMHS) 3, no. 1 (January 13, 2025): 34–55. https://doi.org/10.51317/jmhs.v3i1.638.
Повний текст джерелаАнотація:
The aim of this article is to address the challenges associated with the accurate and consistent staging of the estrous cycle in female laboratory animals, which is critical for reproductive research and preclinical safety evaluations of drugs and chemicals. Laboratory animals, particularly female murine models, are widely used in research as models for mammalian health and disease. However, many substances tested during preclinical investigations interfere with reproductive function, causing morphological changes in the reproductive tract or disruptions in the phases of the estrous cycle. Recognising these alterations requires a thorough understanding of the histological changes in the reproductive tract throughout the cycle. Existing literature, while comprehensive, often lacks precise criteria for defining the transitions between stages of the cycle, creating inconsistencies in staging. This review adopts a pragmatic and practical approach, synthesising personal experience and a century of literature to present a detailed examination of the anatomical and physiological development of the female murine reproductive system. The review emphasises the histological characteristics of the reproductive tract during different estrous phases, providing a framework for consistent and accurate staging. The findings highlight the reproductive traits that make female murine models ideal for reproductive research, including their well-documented physiology and reliable cycle patterns. This article serves as a valuable resource for toxicological pathologists and researchers, offering clarity on staging methods and reaffirming the relevance of murine models in reproductive studies.
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Gong, Fushuai, Wang Yu, Qingpan Zeng, Jiawei Dong, Kun Cao, Hongwei Xu, and Xiaofu Zhou. "Rhododendron chrysanthum’s Primary Metabolites Are Converted to Phenolics More Quickly When Exposed to UV-B Radiation." Biomolecules 13, no. 12 (November 24, 2023): 1700. http://dx.doi.org/10.3390/biom13121700.
Повний текст джерелаАнотація:
The plant defense system is immediately triggered by UV-B irradiation, particularly the production of metabolites and enzymes involved in the UV-B response. Although substantial research on UV-B-related molecular responses in Arabidopsis has been conducted, comparatively few studies have examined the precise consequences of direct UV-B treatment on R. chrysanthum. The ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methodology and TMT quantitative proteomics are used in this study to describe the metabolic response of R. chrysanthum to UV-B radiation and annotate the response mechanism of the primary metabolism and phenolic metabolism of R. chrysanthum. The outcomes demonstrated that following UV-B radiation, the primary metabolites (L-phenylalanine and D-lactose*) underwent considerable changes to varying degrees. This gives a solid theoretical foundation for investigating the use of precursor substances, such as phenylalanine, to aid plants in overcoming abiotic stressors. The external application of ABA produced a considerable increase in the phenolic content and improved the plants’ resistance to UV-B damage. Our hypothesis is that externally applied ABA may work in concert with UV-B to facilitate the transformation of primary metabolites into phenolic compounds. This hypothesis offers a framework for investigating how ABA can increase a plant’s phenolic content in order to help the plant withstand abiotic stressors. Overall, this study revealed alterations and mechanisms of primary and secondary metabolic strategies in response to UV-B radiation.
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Goel, Rajeev. "CRISPR/Cas9-mediated genome editing: from basic research to gene therapy." International Journal of Research in Medical Sciences 12, no. 6 (May 31, 2024): 2200–2211. http://dx.doi.org/10.18203/2320-6012.ijrms20241589.
Повний текст джерелаАнотація:
CRISPR/Cas9 mediated genome editing is one of the most significant molecular tools discovered to edit the desired genes. It has ushered in a new era of novel possibilities of gene therapy. CRISPR/Cas9 system was originally observed as a part of the adaptive immune system in bacteria. It later on was adapted to carry precise and targeted alterations to the DNA in human cells to be used for gene therapy to correct genetic disorders and treat various severe diseases associated with the genetic changes. Besides this, the CRISPR/Cas9 system has been employed in pharmacogenomics to develop new drugs based on the patient’s genes, in modifying the organisms for research and even for diagnostic purposes in developing CRISPR based COVID-9 test. The recent approval of a CRISPR/Cas9 cellular gene therapy by FDA named “Casgevy” to treat sickle cell anemia is a testimonial to the potentials of CRISPR/Cas9 system in developing innovative gene therapies. This review details the mechanisms of CRISPR/Cas9 gene editing and its utilization in the ongoing clinical trials in the treatment of not only the monogenic disorders like sickle cell disease, thalassemia, and genetic blindness but also in treating multi-factorial diseases like cancers, cardiac diseases, diabetes, autoimmune diseases, viral infections such as human immunodeficiency virus (HIV) etc. An attempt has also been made to discuss the various limitations, challenges and ethical frameworks encompassing CRISPR/Cas9 based gene therapy in clinical settings.
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Jiang, Xi, Tuo Zhang, Shu Zhang, Keith M. Kendrick, and Tianming Liu. "Fundamental functional differences between gyri and sulci: implications for brain function, cognition, and behavior." Psychoradiology 1, no. 1 (March 2021): 23–41. http://dx.doi.org/10.1093/psyrad/kkab002.
Повний текст джерелаАнотація:
Abstract Folding of the cerebral cortex is a prominent characteristic of mammalian brains. Alterations or deficits in cortical folding are strongly correlated with abnormal brain function, cognition, and behavior. Therefore, a precise mapping between the anatomy and function of the brain is critical to our understanding of the mechanisms of brain structural architecture in both health and diseases. Gyri and sulci, the standard nomenclature for cortical anatomy, serve as building blocks to make up complex folding patterns, providing a window to decipher cortical anatomy and its relation with brain functions. Huge efforts have been devoted to this research topic from a variety of disciplines including genetics, cell biology, anatomy, neuroimaging, and neurology, as well as involving computational approaches based on machine learning and artificial intelligence algorithms. However, despite increasing progress, our understanding of the functional anatomy of gyro-sulcal patterns is still in its infancy. In this review, we present the current state of this field and provide our perspectives of the methodologies and conclusions concerning functional differentiation between gyri and sulci, as well as the supporting information from genetic, cell biology, and brain structure research. In particular, we will further present a proposed framework for attempting to interpret the dynamic mechanisms of the functional interplay between gyri and sulci. Hopefully, this review will provide a comprehensive summary of anatomo-functional relationships in the cortical gyro-sulcal system together with a consideration of how these contribute to brain function, cognition, and behavior, as well as to mental disorders.
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Nollet, Mathieu, William Wisden, and Nicholas P. Franks. "Sleep deprivation and stress: a reciprocal relationship." Interface Focus 10, no. 3 (April 17, 2020): 20190092. http://dx.doi.org/10.1098/rsfs.2019.0092.
Повний текст джерелаАнотація:
Sleep is highly conserved across evolution, suggesting vital biological functions that are yet to be fully understood. Animals and humans experiencing partial sleep restriction usually exhibit detrimental physiological responses, while total and prolonged sleep loss could lead to death. The perturbation of sleep homeostasis is usually accompanied by an increase in hypothalamic–pituitary–adrenal (HPA) axis activity, leading to a rise in circulating levels of stress hormones (e.g. cortisol in humans, corticosterone in rodents). Such hormones follow a circadian release pattern under undisturbed conditions and participate in the regulation of sleep. The investigation of the consequences of sleep deprivation, from molecular changes to behavioural alterations, has been used to study the fundamental functions of sleep. However, the reciprocal relationship between sleep and the activity of the HPA axis is problematic when investigating sleep using traditional sleep-deprivation protocols that can induce stress per se . This is especially true in studies using rodents in which sleep deprivation is achieved by exogenous, and potentially stressful, sensory–motor stimulations that can undoubtedly confuse their conclusions. While more research is needed to explore the mechanisms underlying sleep loss and health, avoiding stress as a confounding factor in sleep-deprivation studies is therefore crucial. This review examines the evidence of the intricate links between sleep and stress in the context of experimental sleep deprivation, and proposes a more sophisticated research framework for sleep-deprivation procedures that could benefit from recent progress in biotechnological tools for precise neuromodulation, such as chemogenetics and optogenetics, as well as improved automated real-time sleep-scoring algorithms.
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Singer, Stacy D., Madeline Lehmann, Zixuan Zhang, Udaya Subedi, Kimberley Burton Hughes, Nathaniel Z. L. Lim, Rodrigo Ortega Polo, et al. "Elucidation of Physiological, Transcriptomic and Metabolomic Salinity Response Mechanisms in Medicago sativa." Plants 12, no. 10 (May 22, 2023): 2059. http://dx.doi.org/10.3390/plants12102059.
Повний текст джерелаАнотація:
Alfalfa (Medicago sativa L.) is a widely grown perennial leguminous forage crop with a number of positive attributes. However, despite its moderate ability to tolerate saline soils, which are increasing in prevalence worldwide, it suffers considerable yield declines under these growth conditions. While a general framework of the cascade of events involved in plant salinity response has been unraveled in recent years, many gaps remain in our understanding of the precise molecular mechanisms involved in this process, particularly in non-model yet economically important species such as alfalfa. Therefore, as a means of further elucidating salinity response mechanisms in this species, we carried out in-depth physiological assessments of M. sativa cv. Beaver, as well as transcriptomic and untargeted metabolomic evaluations of leaf tissues, following extended exposure to salinity (grown for 3–4 weeks under saline treatment) and control conditions. In addition to the substantial growth and photosynthetic reductions observed under salinity treatment, we identified 1233 significant differentially expressed genes between growth conditions, as well as 60 annotated differentially accumulated metabolites. Taken together, our results suggest that changes to cell membranes and walls, cuticular and/or epicuticular waxes, osmoprotectant levels, antioxidant-related metabolic pathways, and the expression of genes encoding ion transporters, protective proteins, and transcription factors are likely involved in alfalfa’s salinity response process. Although some of these alterations may contribute to alfalfa’s modest salinity resilience, it is feasible that several may be disadvantageous in this context and could therefore provide valuable targets for the further improvement of tolerance to this stress in the future.
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Lomoljo-Bantayan, Nezel Ann, Wella T. Tatil, Frandel Louis S. Dagoc, Annielyn D. Tampus, and Ruben Jr F. Amparado. "Carbon stock assessment of mangrove forests along Macajalar Bay, Misamis Oriental, Philippines." International Journal of ADVANCED AND APPLIED SCIENCES 10, no. 10 (October 2023): 36–45. http://dx.doi.org/10.21833/ijaas.2023.10.004.
Повний текст джерелаАнотація:
Mangrove ecosystems are widely recognized for their crucial role in mitigating climate change through carbon storage and sequestration services. These ecosystems possess significant carbon reservoirs, particularly in their soils. Nevertheless, the unremitting development of coastal areas and alterations in land use constitute impending threats to these ecosystems, endangering the continuity of their invaluable services. Recognizing the crucial role of mangrove ecosystems in mitigating climate change, this study meticulously evaluates the cumulative carbon stocks encompassing the aboveground and soil components within three mangrove-protected areas in the Macajalar Bay region of Misamis Oriental. The study adheres to a logical structure with causal connections between statements, presents information in clear and concise sentences, and follows conventional academic writing formatting. Vocabulary is precise and avoids biased or emotional language. The text adheres to grammatical correctness, consistently uses technical terms, and employs a formal register. The study is free from filler words and employs a passive tone and impersonal construction. Additionally, the text features a consistent footnote style and accurately cites sources. The research findings show that soil carbon makes up a significant portion, ranging from 40% to 90%, of the total carbon stocks in the three study areas. This emphasizes the crucial function of mangrove soils as carbon repositories. Furthermore, the study establishes a direct connection between the age of mangrove stands and the occurrence of large-girth trees, both of which add to the rise in carbon stocks. Despite their substantial carbon storage capacity, mangrove forests in the Macajalar Bay region are still facing encroachments due to urbanization pressures. This assessment of carbon stocks in these coastal ecosystems plays a critical role in developing localized strategies that align with the United Nations Framework Convention on Climate Change's (UNFCCC) REDD+ initiatives, thus preventing further degradation of these vital carbon sinks.
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Nagarajan, Yogeshvaran R., Farukh Farukh, Vadim V. Silberschmidt, Karthikeyan Kandan, Amit Kumar Singh, and Pooja Mukul. "Shape Analysis of Prosthetic Socket Rectification Procedure for Transtibial Amputees." Prosthesis 6, no. 1 (February 5, 2024): 157–74. http://dx.doi.org/10.3390/prosthesis6010013.
Повний текст джерелаАнотація:
Achieving a comfortable socket residual limb interface is crucial for effective prosthetic rehabilitation, depending on the precise characterisation and fluctuations in the shape and volume of residual limbs. Clinicians rely on subjective and iterative methods for shaping sockets, often involving a trial-and-error approach. This study introduces a framework for measuring, analysing, and comparing residual limb shape and volume using scanned data to facilitate more informed clinical decision-making. Surface scans of 44 transtibial residual limb casts of various sizes and lengths were examined. All scans were spatially aligned to a mid-patella and subjected to analysis using a shape analysis toolbox. Geometric measurements were extracted, with particular attention to significant rectified regions during the cast rectification process. Following PTB guidelines, our analysis revealed substantial alterations, primarily in the mid-patella region, followed by the patellar tendon area. Notably, there was a significant volume change of 6.02% in the region spanning from mid-patella to 25% of the cast length. Beyond this point, linear cast modifications were observed for most amputees up to 60% of the cast length, followed by individual-specific deviations beyond this region. Regardless of residual limb size and length, the modifications applied to positive casts suggested categorising patients into five major groups. This study employs the AmpScan shape analysis tool, to comprehend the cast rectification process used for capturing and assessing the extent of rectification on patients’ residual limb casts. The clinical implications of our research are threefold: (a) the comparison data can serve as training resources for junior prosthetists; (b) this will aid prosthetists in identifying specific regions for rectification and assessing socket fit; (c) it will help in determining optimal timing for prosthetic fitting or replacement.
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Chapuy, Bjoern, Chip Stewart, Andrew Dunford, Jaegil Kim, Kirsty Wienand, Atanas Kamburov, Gabriel Kenneth Griffin, et al. "Comprehensive Genomic Analysis of Primary Mediastinal B-Cell Lymphoma." Blood 132, Supplement 1 (November 29, 2018): 1564. http://dx.doi.org/10.1182/blood-2018-99-118135.
Повний текст джерелаАнотація:
Abstract Primary mediastinal large B-cell lymphomas (PMBL) typically occur in young women who present with localized, large mediastinal masses. These tumors share certain clinical, pathomorphological and transcriptional features with classical Hodgkin lymphoma (cHL). To date, PMBL genetic analyses focused on limited sets of genes and recurrent somatic copy number alterations (SCNAs). Previously, we identified frequent 9p24.1/PD-L1/PD-L2 copy gains and increased expression of the PD-1 ligands as a genetically-defined immune escape mechanism in PMBL. The demonstrated efficacy of PD-1 blockade in relapsed/refractory PMBL led to recent FDA approval and underscored the importance of characterizing targetable genetic vulnerabilities in this disease. For these reasons, we obtained diagnostic biopsy specimens from 37 patients with PMBL (median age 34; female 70%) and performed whole exome sequencing (WES) with an expanded bait set to capture structural variants (SVs). Somatic alterations (mutations, SCNAs and SVs) were determined using established analytical pipelines including our algorithm for evaluating tumors without paired normal samples. Genes more frequently mutated than by chance, Candidate Cancer Genes (CCGs), were identified with MutSig2CV and recurrent SCNAs were defined with GISTIC2.0. SVs were characterized with a recently described 4-algorithm pipeline (Nature Medicine, 2018;24(5):679-690). First, we identified 15 CCGs (q-value <0.1) including genes with known roles in PMBL, such as IL4R and TNFAIP3 and mutational drivers in additional B-cell lymphomas (B2M, GNA13, STAT6, IKZF3, XPO1, TP53, PAX5) and other cancers (TP53, ZNF217 and XPO1). Overlaying the predicted protein changes onto available 3D protein structures highlighted the likely biological functions of specific alterations, such as mutational clustering in the STAT6 DNA-binding domain. We next analyzed the PMBL mutational signatures and identified 3 cases as hypermutators with MSI signatures, including 2 with MLH1 frameshift mutations and 1 with a nonsense PMS2 mutation. Despite the young age of the PMBL patient cohort, the majority of remaining mutations were caused by spontaneous deamination at CpGs, a genetic signature usually associated with aging. The next most prevalent mutational signatures were APOBEC and, infrequently, AID. We observed a higher median mutational density in PMBL (7.56 mutations/MB), compared to diffuse large B-cell lymphoma (DLBCL) and most solid cancers, providing a potential basis for increased neoantigen production and responsiveness to PD-1 blockade. Next, we identified 18 recurrent SCNAs, including 10 copy gains (2 focal and 8 arm level) and 8 copy losses (7 focal and 1 arm level). Copy gains of 9p24.1/PD-L1/PD-L2 were detected in 70% of cases. SVs were defined at base-pair resolution and included infrequent (2/37) tandem duplications of both PD-1 ligands and inactivating CTIIA SVs (deletions and inversions) in 10% (4/37) of cases. Although PMBL had a higher mutational density than DLBCL, the PMBL alterations involved a smaller number of median genetic drivers (9 [PMBL] vs 17 [DLBCL], respectively). Combined analyses of recurrent CCGs, SCNAs and SVs revealed that certain candidate driver genes were perturbed by multiple mechanisms. Examples include: TNFAIP3 (59% overall, 41% mutations, 24% copy loss, 6% biallelic); and B2M (51% overall, 30% mutations, 27% copy loss, 6% biallelic). Concurrent analyses of the 3 types of genetic alterations also revealed multiple bases of perturbing specific signaling pathways. In this PMBL series, 73% (27/33) of tumors exhibited one or more alterations of JAK/STAT pathway components: IL4R mutations (32%), JAK2 (9p24.1 focal copy gain [70%]) and STAT6 mutations (43%). Additionally, 59% of PMBLs had alterations of antigen presentation pathway components including B2M copy loss or mutations, copy loss of 6q21.33 (which includes the HLA class I/II loci) and SVs of CTIIA. These findings provide a genetic framework for analyzing the precise mechanism of action of PD-1 blockade in PMBL. Taken together, these findings underscore the importance of a comprehensive genomic analysis in PMBL and define additional candidate treatment targets and pathogenetic mechanisms in this disease. ____ BC, CS and AD contributed equally. GG and MAS contributed equally. Disclosures Rodig: Merck: Research Funding; KITE: Research Funding; Affimed: Research Funding; Bristol Myers Squibb: Research Funding. Shipp:Merck: Research Funding; AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding.
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Udekwe, Charles, and Ponnle Akinlolu. "Development of Landmark-Based Bit-State Model for Shape Analysis and Segmentation of Variations in Intima-Media Thickness of B-Mode Ultrasound Transverse Cross-Section of Carotid Artery Images." Innovation in Science and Technology 3, no. 6 (November 2024): 57–76. https://doi.org/10.56397/ist.2024.11.07.
Повний текст джерелаАнотація:
Central to the assessment of carotid artery health is the measurement of intima-media thickness (IMT), a valuable diagnostic marker for atherosclerosis. IMT quantifies the thickness of two arterial layers — the intima and media — providing insights into arterial wall health and atherosclerotic changes. Carotid ultrasound, a non-invasive imaging technique, is the primary modality for IMT measurement. However, it is not without its challenges, including operator dependency and segmentation difficulties. To surmount these limitations and advance our understanding of carotid artery health, in this research paper, we develop the Bit-State model by applying landmark-based geometric morphometrics (GM) that built upon the foundation of cardinal point symmetry landmark distributed models (CPS-LDM) which we have developed in our previous papers to comprehensively characterize and segment carotid artery IMT, unveiling essential insights into variations and alterations. The Bit-State (BS) Model, revolutionizes our approach to understanding carotid artery structural variations. In this paper, there are four regions of interest (ROI) in the B-Mode carotid artery image, hence we designated each ROI as a bit. Each bit is capable of existing in either of two states: bit 1 as thick-walled and bit 0 as thin-walled ROI. In adopting this binary characterization, we generated 16 different modalities and variations of the ROI of the carotid artery, we then proceed to use the CPS-LD Model to formulate 16 equations for the segmentation of the ROI the carotid artery images. This new model simplifies the complexity of B-Mode ultrasound carotid artery images. It systematically characterizes shape variations using CPS-LDM equations, offering an interpretable framework for comprehending arterial wall composition. This research represents a significant leap forward in carotid artery health assessment, promising more precise diagnoses and targeted interventions for cardiovascular health. It highlights the pivotal role of landmark-based GM in addressing the challenges posed by carotid artery diseases and atherosclerosis. By pioneering this innovative model, this research paves the way for a deeper understanding of carotid artery health and its implications for stroke prevention — a critical stride towards mitigating the global burden of cardiovascular diseases.
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Ananiev, Vitaly G. "Combines of the Leningrad Branch of the USSR Art Fund at the Beginning of the Thaw: Main Activities." Izvestia of the Ural federal university. Series 2. Humanities and Arts 26, no. 4 (2024): 9–26. https://doi.org/10.15826/izv2.2024.26.4.056.
Повний текст джерелаАнотація:
This article examines the activities of the combines of the Leningrad branch of the USSR Art Fund in the mid- to late-1950s. During this period, the Leningrad branch of the USSR Art Fund comprised two combines with responsibilities related to the art industry: the Painting and Sculpture Combine and the Art and Design Combine. The materials preserved in the Central State Archive of Literature and Art of St Petersburg facilitate an understanding of the primary avenues through which the Art Fund influenced the formation of the living environment of Soviet citizens during the period under review. The shift from the period of late Stalinism to the Thaw era was accompanied by substantial alterations in the visual representation and structural configuration of this environment. The analysis of the activities of the combines permits a more precise understanding of the way these images were embodied, implemented, and disseminated at the level of specific production practices. The difficulties faced by the combines were a significant factor in adjusting the ideological framework in which their activities were to be based. The most important problem was the problem of unsatisfactory material and technical base, lack of modern equipment and trained personnel. Despite the government’s stated commitment to the role of decorative, applied, and industrial arts in shaping the living environment of Soviet citizens, the implementation of this policy was hindered by a lack of adequate funding. In many ways, the range of products was formed spontaneously. The artists themselves played a significant role in shaping it. Changes in the subjects and images of the products produced by the combines during the period of the early Thaw make it possible to trace exactly how the formation of the so-called Leningrad style took place. A significant factor here was the postponed celebration of the 250th anniversary of Leningrad, which also became one of the markers of the onset of a new political era. It seems that all the above-mentioned circumstances associated with the actual practices of producing elements of the living environment of a Soviet person should be considered when analysing the general plan of chamber propaganda of the era.
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Alhassan, Abdulaziz, and Hamoud Tannar. "SUBSTANTIVE CRIMINAL PROTECTION FOR THE RIGHT TO IMAGE IN THE DIGITAL ERA UNDER UAE AND FRENCH LEGISLATION." Access to Justice in Eastern Europe 7, no. 2 (April 30, 2024): 325–52. http://dx.doi.org/10.33327/ajee-18-7.2-a000216.
Повний текст джерелаАнотація:
Background: The right to image is considered one of the most important personal rights related to the person, simply because the image does recognise its owner from his or her peers, thus constituting a vital element of one's private life. Accordingly, legal protection of the right to image is highly required on both civil and criminal levels. There is no doubt that such a requirement can be attributed to the notable developments in the field of information technology, and what has been produced by digital devices and misused by people has led to the rapid spread of images in the virtual space, where any individuals have become subject to the violation of their private life. Based on this, the legal provisions of both Emirati and French legislators have adopted legal provisions that would ensure full and substantive criminal protection of the right to image, confirming the criminalisation of all forms of assault on this right, in addition to defining the controls and penalties that shall be applied against these attacks. Methods: To thoroughly tackle our research issue and its consequences, we will employ a descriptive, analytical, and comparative method. This approach is structured to meticulously explore every aspect of the research subject, albeit succinctly, and integrate jurisprudential principles with current judicial precedents. Results and Conclusions: The current research results show that comparative legislation lacks a precise definition concerning the violation of the right to image, thus leaving its interpretation to be determined by jurisprudence and the judiciary. In Emirati and French legal frameworks, this offence is not explicitly delineated but is rather encompassed within regulations safeguarding private life. The right to image is not absolute, with exceptions permitting capturing photographs for public interest. Protection of images is deemed essential within the context of private life rights. While UAE legislation mandates the use of devices for such violations, French law offers flexibility, allowing for various means of perpetration. Both legal systems stipulate that the act must occur in a private, unauthorised context and prohibit alterations to photographs without consent. Unlike UAE law, French legislation imposes penalties for the dissemination of sexually explicit images. Finally, the infringement upon the right to image is categorised as an intentional offence in both legal systems
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Zhang, Jingliao, Peng Wu, Yongjuan Duan, Suyu Zong, Xiaoli Chen, Tianyuan Hu, Wenyu Yang, Renchi Yang, and Yingchi Zhang. "Integrated Single-Cell Long-Read and Short-Read Sequencing Reveals Critical Molecular Characteristics in Pediatric Acute Myeloid Leukemia." Blood 144, Supplement 1 (November 5, 2024): 1561. https://doi.org/10.1182/blood-2024-207727.
Повний текст джерелаАнотація:
Pediatric acute myeloid leukemia (pAML) faced substantial challenges in precise therapeutic decisions making due to the unresolved genetic heterogeneities. As two pevalent subtypes of pAML, mixed-Lineage Leukemia rearrangement (MLLr) and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) AML displayed diversified outcomes as complicated molecular alterations underlined leukemic initiation and progressions, which remained largely unknown. Integrated strategy to dissect molecular pathogenesis from more precisely identified leukemic cells are much needed in large-scale studies. To facilitate this interpretation, the sorted CD34+ bone marrow mononuclear cells (BMMCs) from one pAML with MLLr and one pAML with FLT3-ITD aberrations were initially processed over the 10x Genomics Chromium platform, respectively. The generated Gel Bead-in-Emulsions (GEMs) were divided into two fractions: one was sent for high-throughput droplet-based 5′-single cell RNA-sequencing (scRNA-seq) process, while the other was reserved for Oxford Nanopore long-read library construction and sequencing. To provide a reference framework, single-cell transcriptomic profiles from CD34+ BMMCs of two healthy donors (HDs) were employed and annotated with 14 differential subclusters, based on stage-specific marker genes. By projecting the transcriptional signatures from short-read scRNA-seq onto the previously annotated differential roadmap, CD34+ BMMCs from the two pAML patients predominantly exhibited progenitor and promonocyte/monocyte (Promono/Mono) clusters, aligning with the established understanding differentiation blockade in AML. Noteworthy was the differential inclination across the two subtypes: the FLT3-ITD pAML demonstrated a marked propensity towards stem and progenitor cells, whereas the MLLr subtype did not display this tendency. This distinction underscores the heterogeneity in cellular hierarchies and lineage commitment disruptions accross different genetic subtypes of AML. To confirm the leukemic identities with genetic variations, we analyzed single-cell long-read sequencing data from the second fractions of GEMs, which shared barcodes with cells used for scRNA-seq from the first fractions. In leukemic cells of MLLr pAML, we identified the ELL::KMT2A rearrangement with translocation from breakpoints of the exon 1 of ELL and exon 10 of KMT2A. Meanwhile, leukemic cells from the FLT3-ITD pAML exhibited a tandem repeat of 27 bases within the exon 14 of FLT3 gene. Utilizing 80% of all isolated cells as the training set and the remaining 20% as the test set, we constructed a machine learning model by employing the molecular characteristics of captured leukemia to build a classifier to distinguish leukemia cells from cells without variation identified. Notably, the area under the curve (AUC) of the MLLr leukemic classifier and FLT-ITD altered leukemic classifier both satisfactorily exceeded 0.99, demonstrating their high discriminative performance and reliability in identifying leukemia cells with these specific genetic alterations. Based on internal analysis of the top hits in the classifiers from clinical follow-up data, high MT-ND1 expression in MLLr pAML, and CD99 as a leukemic stemness marker in FLT3-ITD pAML, were further validated to be closely associated with significantly inferior event-free survival and overall survival rate from external TARGET-AML cohort. Our study, leveraging the long-read and short-read single cell sequencing strategies, had profiled full-length transcripts and simultaneously facilitated the reliable detection of gene variations within individual cells, providing a more robust platform for elucidating the heterogeneity and pathogenic mechanisms of different leukemic subtypes. This integration enabled the construction of accurate classifiers to identify leukemia cells based on their subtype-specific molecular characteristics, such as upregulated MT-ND1 and CD99, proposing insights for prognostic assessments and targeted therapies in pAMLs in further investigations.
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Zátopková, Martina, Tereza Sevcikova, Zuzana Kufova, Katerina Growkova, Jana Filipova, Tomas Jelinek, Lucie Říhová, et al. "Whole Exome Sequencing of Residual Disease in Multiple Myeloma: Searching for Novel Therapeutic Targets." Blood 132, Supplement 1 (November 29, 2018): 3175. http://dx.doi.org/10.1182/blood-2018-99-112611.
Повний текст джерелаАнотація:
Abstract Introduction: Multiple myeloma (MM) is a plasma cell dyscrasia causing damage of multiple organs with fatal consequences for patients. Despite the success of modern therapies eliminating a vast bulk of the aberrant cells, surviving residual clones eventually lead to the relapse of the disease. Accumulation of genomic alterations during the stage of minimal residual disease (MRD) likely contributes to a selective grow advantage and survival under the drug pressure. Identification of specific mutations in MM patients with MRD can provide unique opportunities to target the residual plasma cell clones. Here we present the first whole exome sequencing (WES) analysis of 22 MM samples of patients with MRD that identified 814 mutated genes with 4% of genes previously implicated in the pathogenesis of MM. Methods: Aberrant plasma cells (A-PCs) and peripheral blood (PB) were collected from patients after signing informed consent form. Presence of MRD was assessed with EuroFlow protocol and A-PCs were sorted out from bone marrow according to their pathological immunophenotype based on the expression of antigens CD38, CD45, CD19 and CD56. DNA from A-PCs was isolated and amplified by Repli-g Single cell kit (QIAGEN). Sequencing libraries were prepared using SureSelect Human All Exon V6 Kit (Agilent Technologies) and sequenced by Macrogen Inc. on Illumina HiSeq 4000 platform with average coverage 50x and 2x 100bp read length. Sequencing data were processed using the Bcbio framework following the standard workflow for tumor-matched-normal studies. Specifically, reads were mapped to the human reference genome GRCh37, successively marking duplicates using Picard. Germline mutations were identified using GATK HaplotypeCaller, whereas somatic mutations were identified using MuTect2 reporting as significant variants observed in at least 5 reads and minimum allele frequency of 10%. Variants in homopolymer regions longer than 5 nucleotides were filtered out. The final set of calls were further characterised by assessing their functional impact using snpEff and by annotating each variant using data from 1000 Genomes Phase 3, ExAC, and ClinVar. We then used OncodriveCLUST to identify putative oncogenic genes, and later compared these results with a literature curated list of MM driver genes (Weaver & Tariman, 2017). Results: Our dataset comprises 22 samples from 21 patients (one patient was sampled in two time points) with MM MRD, who received bortezomib-based regimen (age 41-71, average 59 years, 11/22 males, 10/22 females). 8 patients reached complete response, 9 patients had very good partial response and 4 patients had partial response. In our analysis, we detected 1,014 tumour somatic variants (8-287 per sample, median 36), most of them being missense mutations (676/1014), splice site mutations (145/1014) and frameshift insertions (134/1014). The variants affected a total of 814 genes, 97 genes were shared in at least two samples. The most frequently mutated genes were KIAA1211 (11/22), the immunoglobulin gene IGLV3-1 (8/22), apoptotic chromatin condensation inducer ACIN1 (7/22) and CCR4-associated factor 3 CNOT3 (7/22). We also identified 32 genes known to be mutated in MM in 64% of our samples (14/22). We found mutations shared by at least 2 samples in KRAS (4/22), DIS3 (3/22), TRAF3 (3/22), NRAS (2/22), ANK2 (2/22), BRAF (2/22) and RBM15 (2/22). Further analysis with OncodriveCLUST identified 18 putative oncogenic genes (FDR < 0.1), including KRAS, DIS3, ACIN1. Conclusion: We presented the first whole exome study of MM MRD, providing a characterisation of the mutations observed in A-PCs. We overcame problem with low amount of A-PCs in this disease stage by using whole genome amplification and a highly customised bioinformatic analysis pipeline. Our study suggests that A-PCs are characterised by new MM MRD specific set of mutated genes, along with the presence of mutations in well-known multiple myeloma cancer driver genes. This offers a great potential for design of novel precise treatments targeting MRD after standard MM therapies. Supported by Ministry of Health of the Czech Republic (17-30089A, CZ-DRO-FNOs/2016) and Ministry of Education of the Czech Republic (SGS18/PřF/2017-2018) Disclosures Kryukov: JSC BIOCAD: Employment. Maisnar:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Hajek:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Research Funding.
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Lobo, Silvana, Rita Barbosa-Matos, Sofia Dória, Ana Maria Pedro, Ana Brito, Daniel Ferreira, and Carla Oliveira. "A protocol for karyotyping and genetic editing of induced pluripotent stem cells with homology-directed repair mediated CRISPR/Cas9." Biology Methods and Protocols, February 28, 2025. https://doi.org/10.1093/biomethods/bpaf018.
Повний текст джерелаАнотація:
Abstract CRISPR/Cas9-mediated homology-directed repair (HDR) allows precise gene editing, but its efficiency remains low for certain cell types, such as human induced pluripotent stem cells (hiPSCs). In this study, we aimed to introduce the CTNNA1: c.2023C>T (p.Q675*) genetic alteration, which is associated with Hereditary Diffuse Gastric Cancer, into hiPSCs using CRISPR/Cas9. We designed a single-guide RNA (sgRNA) targeting the alteration site and a single-stranded oligonucleotide donor DNA template for HDR-based repair. Herein, we report the successful introduction of the CTNNA1: c.2023C>T homozygous alteration in one hiPSC line, which resulted in severe phenotypic changes, including impaired colony formation and cell proliferation. Additionally, we established a straightforward protocol to assess hiPSCs karyotype integrity, ensuring the chromosomal stability required for the gene-editing process. This protocol involves routine G-banding analysis that is required for regular quality controls during handling of hiPSCs. This study demonstrates an efficient approach to precisely edit hiPSCs by CRISPR/Cas9 and highlights the essential role of CTNNA1 expression in maintaining hiPSC viability. Our methodology provides a valuable framework for modeling disease-associated alterations in human-derived cellular models that can be reproduced for other genes and other types of cell lines.
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Borcea, Ciprian S., and Ileana Streinu. "Saturation and periodic self-stress in geometric auxetics." Royal Society Open Science 9, no. 8 (August 2022). http://dx.doi.org/10.1098/rsos.220765.
Повний текст джерелаАнотація:
The auxetic structures considered in this paper are three-dimensional periodic bar-and-joint frameworks. We start with the specific purpose of obtaining an auxetic design with underlying periodic graph of low valency. Adapting a general methodology, we produce an initial framework with valency seven and one degree of freedom. Then, we describe a saturation process, whereby edge orbits are added up to valency 16, with no alteration of the deformation path. This is reflected in a large dimension for the space of periodic self-stresses. The saturated version has higher crystallographic symmetry and allows a precise description of the deformation trajectory. Reducing saturation by adequate removal of edge orbits results in vast numbers of distinct auxetic designs which obey the same kinematics.
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Carrillo Carrión, Carolina, Judit Farrando-Perez, Luke Daemen, Yongqiang Chen, Anibal J. Ramirez-Cuesta, and Joaquin Silvestre-Albero. "Zr‐Porphyrin Metal‐Organic Framework as nanoreactor for boosting the formation of hydrogen clathrates." Angewandte Chemie, December 13, 2023. http://dx.doi.org/10.1002/ange.202315280.
Повний текст джерелаАнотація:
We report the first experimental evidence for rapid formation of hydrogen clathrates under mild pressure and temperature conditions within the cavities of a zirconium‐metalloporphyrin framework, specifically PCN‐222. PCN‐222 has been selected for its 1D mesoporous channels, high water‐stability, and proper hydrophilic behavior. Firstly, we optimize a microwave (MW)‐assisted method for the synthesis of nanosized PCN‐222 particles with precise structure control (exceptional homogeneity in morphology and crystalline phase purity), taking advantage of MW in terms of rapid/homogeneous heating, time and energy savings, as well as potential scalability of the synthetic method. Second, we explore the relevance of the large mesoporous 1D open channels within the PCN‐222 to promote the nucleation and growth of confined hydrogen clathrates. Experimental results show that PCN‐222 drives the nucleation process at a lower pressure than the bulk system (1.35 kbar vs 2 kbar), with fast kinetics (minutes), using pure water, and with a nearly complete water‐to‐hydrate conversion. Unfortunately, PCN‐222 cannot withstand these high pressures, which lead to a significant alteration of the mesoporous structure while the microporous network remains mainly unchanged.
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Carrillo Carrión, Carolina, Judit Farrando-Perez, Luke Daemen, Yongqiang Chen, Anibal J. Ramirez-Cuesta, and Joaquin Silvestre-Albero. "Zr‐Porphyrin Metal‐Organic Framework as nanoreactor for boosting the formation of hydrogen clathrates." Angewandte Chemie International Edition, December 13, 2023. http://dx.doi.org/10.1002/anie.202315280.
Повний текст джерелаАнотація:
We report the first experimental evidence for rapid formation of hydrogen clathrates under mild pressure and temperature conditions within the cavities of a zirconium‐metalloporphyrin framework, specifically PCN‐222. PCN‐222 has been selected for its 1D mesoporous channels, high water‐stability, and proper hydrophilic behavior. Firstly, we optimize a microwave (MW)‐assisted method for the synthesis of nanosized PCN‐222 particles with precise structure control (exceptional homogeneity in morphology and crystalline phase purity), taking advantage of MW in terms of rapid/homogeneous heating, time and energy savings, as well as potential scalability of the synthetic method. Second, we explore the relevance of the large mesoporous 1D open channels within the PCN‐222 to promote the nucleation and growth of confined hydrogen clathrates. Experimental results show that PCN‐222 drives the nucleation process at a lower pressure than the bulk system (1.35 kbar vs 2 kbar), with fast kinetics (minutes), using pure water, and with a nearly complete water‐to‐hydrate conversion. Unfortunately, PCN‐222 cannot withstand these high pressures, which lead to a significant alteration of the mesoporous structure while the microporous network remains mainly unchanged.
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Chukanov, Nikita V., Ramiza K. Rastsvetaeva, Natalia V. Zubkova, Marina F. Vigasina, Igor V. Pekov, Andrey A. Zolotarev, Julia A. Mikhailova, and Sergey M. Aksenov. "Spectroscopic characterization of extra‐framework hydrated proton complexes with the extremely strong hydrogen bonds in microporous silicate minerals." Journal of Raman Spectroscopy, January 22, 2024. http://dx.doi.org/10.1002/jrs.6656.
Повний текст джерелаАнотація:
AbstractMicroporous materials containing hydrated silanol groups Si–OH as well as hydrated proton complexes, H2n+1On+, including hydronium (n = 1), Zundel (n = 2), and Eigen (n = 4) cations, are of practical importance as potential ion exchangers and ion conductors. In this paper, we provide data on crystal‐chemical features, hydrogen bonding and Raman spectra of alkaline microporous titano‐, niobo‐, zircono‐, and aluminosilicate minerals belonging to the labuntsovite, lovozerite, eudialyte, and sodalite groups in which a part of sodium was substituted by hydrated proton complexes under low‐temperature hydrothermal or supergene conditions. Most minerals studied in this work do not have synthetic analogues and are considered as possible natural prototypes of microporous materials with technologically important properties. The obtained experimental data and their comparison with the results of ab initio theoretical calculations published elsewhere show that Raman spectroscopy is an effective tool for the precise identification of hydrated proton complexes with extremely strong hydrogen bonds and estimation of corresponding O···O distances in the range of 2.37–2.68 Å. The presence of hydrated proton complexes in microporous silicates is a clear and sensitive geological indicator showing that a rock underwent the low‐temperature alteration.
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Krishna Chimata, Murali, and Amita Prasad. "Regulation of genome-edited technologies: Indian policy perspective." Current Indian Science 01 (February 23, 2023). http://dx.doi.org/10.2174/2210299x01666230223105053.
Повний текст джерелаАнотація:
Abstract: The rapid technological advances in the field of biotechnology have resulted in the formulation of effective and robust regulatory policy frameworks by different countries to ensure the safety of the products that are being developed through the application of genome editing techniques both in terms of environment and health safety perspectives. With over two and half decades of use of products derived from the application of genetic engineering technologies, this technology has stemmed the emergence of an even more advanced and precise targeted technology to address the most complicated and intrinsic challenges in a more precise manner which is now considered as Genome Editing. It is astounding to note that, at a time when several nations were debating and discussing the regulatory hurdles regarding the regulation of this technology, India has emerged as one nation with a clear policy framework with well-defined definitions in Rules 1989 itself, wherein, the definition of Gene Technology and Genetic Engineering clearly states that any alteration in the genome needs to be regulated and accordingly, India needs to regulate the products that would be developed through this novel genome editing technology. However, recognizing the global developments and after a thorough assessment of safety aspects, India, in the year 2022 promulgated the “ Guidelines for the Safety Assessment of Genome Edited Plants” wherein, it is explicitly detailed that products that are derived from SDN-1 and SDN-2 techniques and which are free of exogenous, introduced the DNA that is exempted from the provisions of Rules 7 to 11 (both inclusive) of the above said Rules 1989 and products derived from SDN-3 would be regulated as per provisions of Rules, 1989. If required, the concerned regulatory agencies may stipulate additional safety evaluation tests through better risk evaluation methodologies and a greater number of laboratories could also be set up along with empowering the human resource capacities for undertaking such state-of-the-art and precise techniques for the development of safe and beneficial products for the public without compromising on the safety.