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In this work, we present a mechanobiochemical model for two-dimensional cell migration which couples mechanical properties of the cell cytosol with biochemical processes taking place near or on the cell plasma membrane. The modelling approach is based on a recently developed mathematical formalism of evolving bulk-surface partial differential equations of reaction-diffusion type. We solve these equations using finite element methods within a moving-mesh framework derived from the weak formulation of the evolving bulk-surface PDEs. In the present work, the cell cytosol interior (bulk) dynamics are coupled to the cell membrane (surface) dynamics through non-homogeneous Dirichlet boundary conditions. The modelling approach exhibits both directed cell migration in response to chemical cues as well as spontaneous migration in the absence of such cues. As a by-product, the approach shows fundamental characteristics associated with single cell migration such as: (i) cytosolic and membrane polarisation, (ii) actin dependent protrusions, and (iii) continuous shape deformation of the cell during migration. Cell migration is an ubiquitous process in life that is mainly triggered by the dynamics of the actin cytoskeleton and therefore is driven by both mechanical and biochemical processes. It is a multistep process essential for mammalian organisms and is closely linked to a vast diversity of processes; from embryonic development to cancer invasion. Experimental, theoretical and computational studies have been key to elucidate the mechanisms underlying cell migration. On one hand, rapid advances in experimental techniques allow for detailed experimental measurements of cell migration pathways, while, on the other, computational approaches allow for the modelling, analysis and understanding of such observations. The bulk-surface mechanobiochemical modelling approach presented in this work, set premises to study single cell migration through complex non-isotropic environments in two- and three-space dimensions.
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Objectives: Levonadifloxacin (IV) and alalevonadifloxacin (oral) are novel broad-spectrum anti-methicillin-resistant Staphylococcus aureus (S. aureus) agents based on novel benzoquinolizine core. Both are recently approved in India for the treatment of acute bacterial skin and skin structure infections, including diabetic foot infections and concurrent bacteremia. The present investigation reports the findings from preclinical pharmacokinetic (PK) studies that support the development of levonadifloxacin as a treatment option for bone and joint infections (BJIs). Methods: PK profiles of levonadifloxacin were obtained in serum, and/or various anatomical segments of femoral bone such as whole bone (WB), hard bone (HB), and bone marrow (BM) following subcutaneous administration of levonadifloxacin single doses at 50, 100, 200, and 400 mg/kg, as well as multiple doses at 200 mg/kg (BID (two times a day), 6 hours apart) for 5 days in Wistar rats. Results: The distribution of levonadifloxacin in bone was rapid, and the extent of distribution (B/S ratio; bone-to-serum area under the concentration-time curve ratio) was nearly comparable across bone segments. In single-dosage PK studies, the mean B/S ratio in WB, HB, and BM was 0.40, 0.33, and 0.34, respectively; however, in 5 days' repeated dose studies, it increased to 1.01, 1.14, and 0.61, respectively. Conclusions: On the basis of bone PK data in Wistar rat and ever-growing clinical experience in terms of safety and efficacy, levonadifloxacin has the potential to offer a well-differentiated therapy for the treatment of BJIs.
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PICK1 plays a crucial role in mammalian spermatogenesis. Here, we integrated single-molecule long-read and short-read sequencing to comprehensively examine PICK1 expression patterns in adult Baoshan pig (BS) testes. We identified the most important transcript ENSSSCT00000000120 of PICK1, obtaining its full-length coding sequence (CDS) spanning 1254 bp. Gene structure analysis located PICK1 on pig chromosome 5 with 14 exons. Protein structure analysis reflected that PICK1 consisted of 417 amino acids containing two conserved domains, PDZ and BAR_PICK1. Phylogenetic analysis underscored the evolutionary conservation and homology of PICK1 across different mammalian species. Evaluation of protein interaction network, KEGG, and GO pathways implied that interacted with 50 proteins, predominantly involved in glutamatergic synapses, amphetamine addiction, neuroactive ligand-receptor interactions, dopaminergic synapses, and synaptic vesicle recycling, and PICK1 exhibited significant correlation with DLG4 and TBC1D20. Functional annotation identified that PICK1 was involved in 9 GOs, including seven cellular components and two molecular functions. ceRNA network analysis suggested BS PICK1 was regulated by seven miRNA targets. Moreover, qPCR expression analysis across 15 tissues highlighted that PICK1 was highly expressed in the bulbourethral gland and testis. Subcellular localization analysis in ST (Swine Tesits) cells demonstrated that PICK1 significantly localized within the cytoplasm. Overall, our findings shed new light on PICK1's role in BS reproduction, providing a foundation for further functional studies of PICK1.
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Prolyl oligopeptidase, or S9 (MEROPS) family enzymes are crucial drug targets due to their association with various diseases, neurological disorders, cell growth, and survival. These implications render them an exceptionally fascinating field of research. Despite sharing similar structural features, they exhibit diverse enzyme activities, including endopeptidase, dipeptidyl peptidase, and acylaminoacyl peptidase. Additionally, a few members of the S9 family demonstrate carboxypeptidase activity. A recent study showed that the S9 peptidase of Bacillus subtilis (S9bs) possesses the conserved sequence feature necessary for carboxypeptidase activity despite being annotated as an acylaminoacyl peptidase in the UniProt database. However, the mechanism of action and identity of S9bs as carboxypeptidase remain unclear. Consequently, we focused our studies on thoroughly investigating S9bs for its carboxypeptidase activity. In the present study, we report biochemical and biophysical analyses of S9bs, confirming its identity as a carboxypeptidase. Further, structural analysis reveals the molecular basis of S9bs' carboxypeptidase activity, highlighting the crucial structural elements like the "cavity loop" and the "two-arginine" residues essential for this activity. Additionally, our studies confirmed that S9bs forms a stable tetrameric assembly and established its quaternary molecular arrangement, which reveals the presence of an oligomeric pore. Altogether, these structural features play a are crucial role in substrate selection for S9 carboxypeptidases. Overall, our findings reveal a distinct carboxypeptidase within the S9 family and significantly enhance our understanding of these enzymes. Moreover, this study sheds light on the mechanisms underlying carboxypeptidase activity, offering valuable insights that could contribute to therapeutic and drug design.
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Vitamin Bs, a group of water-soluble compounds, are essential nutrients for almost all living organisms. However, due to their structural heterogeneity, rapid and simultaneous analysis of multiple vitamin Bs is still challenging. In this paper, it is discovered that a hetero-octameric Mycobacterium smegmatis porin A (MspA) nanopore containing a sole nickel ion-bound nitrilotriacetic acid (NTA-Ni) adapter at its pore constriction is suitable for the simultaneous sensing of different vitamin Bs, including vitamin B1 (thiamine), vitamin B3 (nicotinic acid and nicotinamide), vitamin B5 (pantothenic acid), and vitamin B6 (pyridoxine, pyridoxal, and pyridoxamine). Assisted by a custom machine learning algorithm, all seven vitamin Bs can be fully distinguished, reporting a general accuracy of 99.9%. This method was further validated in the rapid analysis of commercial cosmetics and natural food, suggesting its potential uses in food and drug administration.
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Nanoporos , Vitamina B 6 , Vitamina B 6/análise , Vitamina B 6/química , Porinas/química , Mycobacterium smegmatis , Tiamina/análise , Tiamina/química , Aprendizado de Máquina , Niacinamida/análise , Niacinamida/químicaRESUMO
In Egypt, while many studies have focused on the radiometry and mineralogy of black sands, research on their effects on nearby aquatic organisms is rare. This study aimed to assess the combined effects of heat stress (HS) and black sand nanoparticles (BS-NPs) on renal function, antioxidant responses (TAC, SOD, CAT), neuro-stress indicators (AchE, cortisol), and to conduct histopathological investigations in the kidney and spleen tissues of African catfish Clarias gariepinus over a 15-day period to exposure to control, HS (32 °C), BS (6.4 g/kg diet) and HS + BS groups. The outcomes revealed that thermal stress alone showed no significant difference from the control. However, creatinine and uric acid levels were significantly higher in the BS-NPs and HS + BS-NPs groups (p < 0.001). Antioxidant markers (TAC, SOD, and CAT) were substantially reduced across all treated groups (0.05 ≥ p < 0.0001). AchE levels were significantly elevated in BS-NPs and HS + BS-NPs (p < 0.001), while cortisol levels were higher in these groups but not significantly different in HS. Degeneration and necrosis in the white and red pulps, scattered lymphocytes, and increased collagen fiber surrounding blood vessels and the lining of the ellipsoid structure were all evident in the spleen, along with the enlargement of the melanomacrophage centers with big granular, irregular, and brown pigments (hemosiderin). Our study, therefore, provides new insights into how heat stress, an abiotic environmental factor, influences the toxicity of black sand nanoparticles in catfish.
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Peixes-Gato , Resposta ao Choque Térmico , Rim , Nanopartículas , Estresse Oxidativo , Baço , Animais , Peixes-Gato/metabolismo , Baço/patologia , Baço/metabolismo , Rim/patologia , Rim/metabolismo , Areia , Antioxidantes/metabolismo , Dióxido de SilícioRESUMO
This study presents a novel approach for the eco-friendly green synthesis of copper nanoparticles (Cu NPs) using enzymatic mediation which is an environmentally benign alternative to conventional methods, offering control over particle size and shape. Anoxybacillus rupiensis BS1 thermophilic bacterium was isolated from Erzurum's Pasinler hot spring and lignin peroxidase enzyme production conditions (incubation time 96 h, 40 g/L shell amount, pH 8.5, 150 rpm, and 60 °C temperature) were used in the production of peroxidase enzyme using peanut waste which has been optimized. The characterization of the synthesized Cu NPs was performed using various analytical techniques, including UV-vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM), confirming the successful production of stable and well-defined nanoparticles. Furthermore, the biological activities of the synthesized Cu NPs were explored, revealing their potential for antimicrobial applications. The antibacterial efficacy of the Cu NPs against some pathogens such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, and Bacillus cereus was examined. It was determined that Cu NPs were effective on all pathogens and had the highest effectiveness against the S. pyogenes pathogen (19.0 mm). This study not only presents an innovative and sustainable approach for the synthesis of Cu NPs but also highlights the multifaceted biological activities of these nanoparticles, opening avenues for diverse applications in the fields of medicine, agriculture, and environmental remediation. The utilization of peanut shell wastes as a substrate for enzyme production adds value to agricultural by-products, contributing to the development of a circular and sustainable economy.
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Anoxybacillus , Arachis , Cobre , Nanopartículas Metálicas , Cobre/química , Nanopartículas Metálicas/química , Peroxidases/metabolismo , Química Verde , Perda e Desperdício de AlimentosRESUMO
High-temperature ultrasonic transducer (HTUT) is essential for non-destructive testing (NDT) in harsh environments. In this paper, a HTUT based on BiScO3-PbTiO3 (BS-PT) piezoelectric ceramics was developed, and the effect of different backing layers on its bandwidth were analyzed. The HTUT demonstrates a broad bandwidth and excellent thermal stability with operation temperature up to 400 °C. By using a 10 mm thick porous alumina backing layer, the HTUT achieves a broad -6 dB bandwidth of 100 %, which is about 4 times superior to the transducer with an air backing layer. The center frequency (fc) of the HTUT remains stable with fluctuations of less than 10 % across the temperature range from room temperature to 400 °C. The HTUT successfully detected simulated defects in pulse-echo mode for NDT over 200 °C. This research not only advances high-temperature ultrasonic transducer technology but also expands the NDT applications in harsh environmental conditions.
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BACKGROUND: Bacterial spot of pepper (BSP), caused by four different Xanthomonas species, primarily X. euvesicatoria (Xe), poses a significant challenge in pepper cultivation. Host resistance is considered the most important approach for BSP control, offering long-term protection and sustainability. While breeding for resistance to BSP for many years focused on dominant R genes, introgression of recessive resistance has been a more recent focus of breeding programs. The molecular interactions underlying recessive resistance remain poorly understood. RESULTS: In this study, transcriptomic analyses were performed to elucidate defense responses triggered by Xe race P6 infection by two distinct pepper lines: the Xe-resistant line ECW50R containing bs5, a recessive resistance gene that confers resistance to all pepper Xe races, and the Xe-susceptible line ECW. The results revealed a total of 3357 upregulated and 4091 downregulated genes at 0, 1, 2, and 4 days post-inoculation (dpi), with the highest number of differentially expressed genes (DEGs) observed at 2 dpi. Pathway analysis highlighted DEGs in key pathways such as plant-pathogen interaction, MAPK signaling pathway, plant hormone signal transduction, and photosynthesis - antenna proteins, along with cysteine and methionine metabolism. Notably, upregulation of genes associated with PAMP-Triggered Immunity (PTI) was observed, including components like FLS2, Ca-dependent pathways, Rboh, and reactive oxygen species (ROS) generation. In support of these results, infiltration of ECW50R leaves with bacterial suspension of Xe led to observable hydrogen peroxide accumulation without a rapid increase in electrolyte leakage, suggestive of the absence of Effector-Triggered Immunity (ETI). Furthermore, the study confirmed that bs5 does not disrupt the effector delivery system, as evidenced by incompatible interactions between avirulence genes and their corresponding dominant resistant genes in the bs5 background. CONCLUSION: Overall, these findings provide insights into the molecular mechanisms underlying bs5-mediated resistance in pepper against Xe and suggest a robust defense mechanism in ECW50R, primarily mediated through PTI. Given that bs5 provides early strong response for resistance, combining this resistance with other dominant resistance genes will enhance the durability of resistance to BSP.
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Capsicum , Resistência à Doença , Perfilação da Expressão Gênica , Doenças das Plantas , Xanthomonas , Capsicum/genética , Capsicum/microbiologia , Capsicum/imunologia , Resistência à Doença/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Regulação da Expressão Gênica de Plantas , TranscriptomaRESUMO
Customer satisfaction is an important criterion to measure the service quality of bed and breakfasts (B&Bs). How to assess the customer satisfaction of B&Bs scientifically has always been a worthy topic. Based on the national standard, this study constructed an evaluation index system of customer satisfaction of island B&Bs consisting of 5 dimensions and 23 indicators. After SEM verification, the index system exhibited a good fit, and the dimensions of atmosphere, service, security, facilities, and characteristics had a significant positive effect on the customer satisfaction of the island B&Bs. At the same time, customer satisfaction of island B&Bs significantly and positively affected customers' post-purchase psychological perceptions, such as overall evaluation, repurchase intention, and recommendation intention. Then, the IPA method was used to analyze the importance and satisfaction of each index of customer satisfaction of Fujian island B&Bs. The results showed that island B&Bs in Fujian had strong advantages in the island atmosphere, guest services and facilities, and the most urgent index to be improved was the light and sound insulation of the guest rooms, and the featured items such as specialty food and beverage, customized activities, and specialty cultural and creative sales also needed to be improved. The index system provides a scientific method for the customer satisfaction evaluation of the island B&Bsï¼and it will effectively guide the operation and management of the island B&Bs operators.
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Comportamento do Consumidor , Humanos , China , Adulto , Feminino , Masculino , Satisfação Pessoal , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. METHODS AND RESULTS: The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). CONCLUSIONS: In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina Antirrábica , Vírus da Raiva , Raiva , Vírus da Raiva/imunologia , Vírus da Raiva/genética , Vírus da Raiva/patogenicidade , Animais , Vacina Antirrábica/imunologia , Vacina Antirrábica/genética , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Raiva/prevenção & controle , Raiva/imunologia , Raiva/virologia , Humanos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Chlorocebus aethiops , Virulência , Vacinas de Produtos Inativados/imunologia , Células Vero , China , Camundongos , Linhagem Celular , Mutação , Feminino , Imunogenicidade da VacinaRESUMO
Osteoporosis is the most prevalent skeletal disorder, a condition that is associated with significant social and healthcare burden. In the elderly, osteoporosis is commonly associated with sarcopenia, further increasing the risk of fracture. Several imaging techniques are available for a non-invasive evaluation of osteoporosis and sarcopenia. This review focuses on dual-energy X-ray absorptiometry (DXA), as this technique offers the possibility to evaluate bone mineral density and body composition parameters with good precision and accuracy. DXA is also able to evaluate the amount of aortic calcification for cardiovascular risk estimation. Additionally, new DXA-based parameters have been developed in recent years to further refine fracture risk estimation, such as the Trabecular Bone Score and the Bone Strain Index. Finally, we describe the recent advances of a newly developed ultrasound-based technology known as Radiofrequency Echographic Multi-Spectrometry, which represent the latest non-ionizing approach for osteoporosis evaluation at central sites.
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Absorciometria de Fóton , Densidade Óssea , Osteoporose , Humanos , Absorciometria de Fóton/métodos , Osteoporose/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem , Composição Corporal , Ultrassonografia/métodos , Medição de RiscoRESUMO
In base-station-based underwater wireless acoustic networks (B-UWANs), effective handover mechanisms are necessary to ensure seamless data services for mobile nodes such as autonomous underwater vehicles (AUVs). Unlike terrestrial base stations (BSs), moored buoy BSs in B-UWANs experience motion responses due to wave loads under environmental conditions, posing unique challenges to the handover process. This study examines how BS motion affects handover decision errors, which arise when AUVs incorrectly initiate handovers to unintended BSs due to BS motion. By utilizing the AUV-BS distance as a handover triggering parameter, our analysis reveals a significant increase in decision errors within the overlapping regions when both the current and target BSs are in motion, especially when moving in the same direction. In addition, these errors intensify with the magnitude of BS motion and are exacerbated by smaller BS network radii. Based on these simulation results, we present an analytical framework that not only measures the influence of BS motion on the AUV-BS distance but also provides strategic insights for refining underwater handover protocols, thereby enhancing operational reliability and service continuity in B-UWANs.
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Previous studies have suggested an association between Proton Pump Inhibitors (PPIs) and the progression of chronic kidney disease (CKD). This study aims to assess the association between PPI use and CKD progression by analysing estimated glomerular filtration rate (eGFR) trajectories using a process mining approach. We conducted a retrospective cohort study from 1 January 2006 to 31 December 2011, utilising data from the Stockholm Creatinine Measurements (SCREAM). New users of PPIs and H2 blockers (H2Bs) with CKD (eGFR < 60) were identified using a new-user and active-comparator design. Process mining discovery is a technique that discovers patterns and sequences in events over time, making it suitable for studying longitudinal eGFR trajectories. We used this technique to construct eGFR trajectory models for both PPI and H2B users. Our analysis indicated that PPI users exhibited more complex and rapidly declining eGFR trajectories compared to H2B users, with a 75% increased risk (adjusted hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.49 to 2.06) of transitioning from moderate eGFR stage (G3) to more severe stages (G4 or G5). These findings suggest that PPI use is associated with an increased risk of CKD progression, demonstrating the utility of process mining for longitudinal analysis in epidemiology, leading to an improved understanding of disease progression.
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The deprotonation of O6 within the S3 state marks the final deprotonation event before the formation of oxygenoxygen bond interactions and eventual production and release of dioxygen. Gaining a thorough understanding of this event, from the proton acceptors involved, to the exfiltration pathways available, is key in determining the nature of the resulting oxygen species, influencing the mechanism through which the first oxygenoxygen bond forms. Computational analysis, using BS-DFT methodologies, showed that proton abstraction by the local Glu189 residue provides consistent evidence against this being a viable mechanistic pathway due to the lack of a stable product structure. In contrast, abstraction via W3 shows an increasingly stable oxo-oxo product state between r[O5O6] = 2.1 Å & 1.9 Å. The resulting oxo-oxo state is stabilised through donation of ß electron character from O6 to Mn1 and α electron character from O6 to O5. This donation from the O6 lone pair is shown to be a key factor in stabilising the oxo-oxo state, in addition to showing the initiation of first O5-O6 bond.
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Oxigênio , Complexo de Proteína do Fotossistema II , Prótons , Complexo de Proteína do Fotossistema II/química , Complexo de Proteína do Fotossistema II/metabolismo , Oxigênio/química , Oxigênio/metabolismo , Teoria da Densidade Funcional , Modelos MolecularesRESUMO
BACKGROUND: Bisulfite sequencing (BS-Seq) is a fundamental technique for characterizing DNA methylation profiles. Genotype calling from bisulfite-converted BS-Seq data allows allele-specific methylation analysis and the concurrent exploration of genetic and epigenetic profiles. Despite various methods have been proposed, single nucleotide polymorphisms (SNPs) calling from BS-Seq data, particularly for SNPs on chromosome X and in the presence of contaminative data, poses ongoing challenges. RESULTS: We introduce bsgenova, a novel SNP caller tailored for bisulfite sequencing data, employing a Bayesian multinomial model. The performance of bsgenova is assessed by comparing SNPs called from real-world BS-Seq data with those from corresponding whole-genome sequencing (WGS) data across three human cell lines. bsgenova is both sensitive and precise, especially for chromosome X, compared with three existing methods. Moreover, in the presence of low-quality reads, bsgenova outperforms other methods notably. In addition, bsgenova is meticulously implemented, leveraging matrix imputation and multi-process parallelization. Compared to existing methods, bsgenova stands out for its speed and efficiency in memory and disk usage. Furthermore, bsgenova integrates bsextractor, a methylation extractor, enhancing its flexibility and expanding its utility. CONCLUSIONS: We introduce bsgenova for SNP calling from bisulfite-sequencing data. The source code is available at https://github.com/hippo-yf/bsgenova under license GPL-3.0.
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Metilação de DNA , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Sulfitos , Humanos , Metilação de DNA/genética , Sulfitos/química , Análise de Sequência de DNA/métodos , Genótipo , Software , Sequenciamento Completo do Genoma/métodos , Teorema de BayesRESUMO
Background: Bartter syndrome is an autosomal recessive salt reabsorption disorder that results in decreased extracellular fluid volume with low/normal blood pressure. Case presentation: A 17-year-old boy with polydipsia, polyuria, weakness in the lower limbs, and ataxic gait. His Laboratory test shows hypokalemia; hypochloremia, hypomagnesemia and metabolic alkalosis. The authors' patient was managed by fluid and electrolyte replacement, which is essential in emergency management. Conclusion: Bartter syndrome is difficult to treat, and currently, there is no complete cure. The overall prognosis depends on the extent of receptor dysfunction, and despite these facts, most patients can live a normal life if they strictly follow their treatment plan.
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Nucleotide conversion RNA sequencing techniques interrogate chemical RNA modifications in cellular transcripts, resulting in mismatch-containing reads. Biases in mapping the resulting reads to reference genomes remain poorly understood. We present splice_sim, a splice-aware RNA-seq simulation and evaluation pipeline that introduces user-defined nucleotide conversions at set frequencies, creates mixture models of converted and unconverted reads, and calculates mapping accuracies per genomic annotation. By simulating nucleotide conversion RNA-seq datasets under realistic experimental conditions, including metabolic RNA labeling and RNA bisulfite sequencing, we measure mapping accuracies of state-of-the-art spliced-read mappers for mouse and human transcripts and derive strategies to prevent biases in the data interpretation.
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RNA-Seq , Camundongos , Animais , Humanos , RNA-Seq/métodos , Splicing de RNA , Análise de Sequência de RNA/métodos , Software , Nucleotídeos/genética , Simulação por ComputadorRESUMO
This paper proposes a new contribution in the field of optimizing control techniques for wind systems to enhance the quality of the energy produced in the grid. Although the Sliding Mode control technique, whether classical or involving the use of artificial intelligence, has shown interesting results, its main drawback lies in the oscillation phenomenon commonly referred to as "chattering." This phenomenon affects the accuracy and robustness of the system, as well as the parametric variation of the system. In this work, we propose a solution that combines two nonlinear techniques based on the Lyapunov theorem to eliminate the chattering phenomenon. It is a hybrid approach between the Backstepping strategy and the Sliding Mode, aiming to control the active and reactive powers of the doubly fed induction generator (DFIG) connected to the electrical grid by two converters (grid side and machine side). This hybrid technique aims to improve the performance of the wind system in terms of precision errors, stability, as well as active and reactive power. The proposed solution has been validated in the Matlab & Simulink environment to assess the performance and robustness of the proposed model, as well as experimentally validated on a test bench using the DSPACE 1104 card. The obtained results are then compared with other techniques, demonstrating a significant improvement in performance.