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1.
Sci Rep ; 14(1): 13129, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849414

RESUMEN

Over the past decades, the software industry has expanded to include all industries. Since stakeholders tend to use it to get their work done, software houses seek to estimate the cost of the software, which includes calculating the effort, time, and resources required. Although many researchers have worked to estimate it, the prediction accuracy results are still inaccurate and unstable. Estimating it requires a lot of effort. Therefore, there is an urgent need for modern techniques that contribute to cost estimation. This paper seeks to present a model based on deep learning and machine learning techniques by combining convolutional neural networks (CNN) and the particle swarm algorithm (PSO) in the context of time series forecasting, which enables feature extraction and automatic tuning of hyperparameters, which reduces the manual effort of selecting parameters and contributes to fine-tuning. The use of PSO also enhances the robustness and generalization ability of the CNN model and its iterative nature allows for efficient discovery of hyperparameter similarity. The model was trained and tested on 13 different benchmark datasets and evaluated through six metrics: mean absolute error (MAE), mean square error (MSE), mean magnitude relative error (MMRE), root mean square error (RMSE), median magnitude relative error (MdMRE), and prediction accuracy (PRED). Comparative results reveal that the performance of the proposed model is better than other methods for all datasets and evaluation criteria. The results were very promising for predicting software cost estimation.

2.
Heart Rhythm ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38823667

RESUMEN

BACKGROUND: Atrial fibrillation (AF) ablation carries the risk of silent cerebral event (SCE) and silent cerebral lesion (SCL). Although "silent," these may have long-term clinical implications and are challenging to study as postprocedural magnetic resonance imaging (MRI) is not standard of care. OBJECTIVE: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) with standard-of-care thermal ablation. METHODS: The NAS included consecutive randomized PFA and thermal ablation patients who received postprocedural brain MRI 12-48 hours after ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin scale assessment. MRI images were subsequently reviewed by a blinded brain imaging core laboratory. RESULTS: In total, 77 patients with paroxysmal AF were enrolled at 6 centers; 71 had analyzable scans (34 PFA; 37 thermal ablation). Through individual center review, 6 PFA and 4 thermal scans were identified as SCE/SCL positive, of which 3 PFA and 0 thermal SCE/SCL findings were confirmed by a blinded core laboratory. MRI findings revealed 1 patient with 2- to 4-mm SCEs, 1 patient with a 3-mm SCE, and 1 patient with 2 SCLs (5.5 mm and 11 mm). All modified Rankin scale and National Institutes of Health Stroke Scale scores were 0 before discharge and at 90-day follow-up. There were only 2 neurological safety events (1 transient ischemic attack [PFA] and 1 stroke [thermal ablation]) in the ADVENT study, neither of which was part of the NAS. CONCLUSION: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCL after ablation in the NAS was low.

3.
J Thorac Dis ; 16(3): 1996-2003, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38617780

RESUMEN

Background: The Nuss procedure is currently the mainstream of pectus excavatum (PE) surgery; however, it is considered to be more difficult for asymmetric cases than for symmetric ones. Sternocostal elevation (SCE), which was performed at our hospital, is a surgical method that determines the extent of resection of the costal cartilage while comparing the left and right balance during surgery; thus, it is highly useful for correcting rib cage with strong asymmetry. Methods: Of the 256 patients who underwent SCE at our hospital between July 2014 and July 2022, 58 (22.7%) with asymmetric PE were retrospectively examined. However, patients with advanced scoliosis having a Cobb angle of 25° or higher were excluded; therefore, 51 (19.9%) patients were analyzed. Two indices and other measurements were evaluated to determine the success of correction for asymmetry using computed tomography (CT). Results: The difference between the left and right thoraxes, the Haller index, and the sternal torsion angle significantly improved. Furthermore, we herein set a new numerical index as an indicator of asymmetry improvement and to be used for a more standard thorax morphology; the difference between the left and right thoraxes/the average of the left and right thoraxes. That new index also significantly improved. Conclusions: SCE is considered a highly useful surgical method for asymmetric PE.

4.
Int J Womens Health ; 16: 637-644, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645979

RESUMEN

Purpose: Fragile sites are specific chromosomal regions showing gaps, poor staining, contractions, or even breaks in the chromosomes. These spontaneous and heritable fragile sites are prone to structural variations which can lead to adverse reproductive outcomes. This paper aims to present a specific case study of a female patient, with a mosaic karyotype involving chromosome 16q22 fragile site which is very rare in clinic and her experience of infertility. Case Presentation: A 37-year-old woman is diagnosed with ten-year primary infertility. She worked in a factory, and she was occasionally exposed to paint. She underwent two cycles of follicular monitoring with intrauterine insemination (IUI) using her husband's sperm six years ago but failed. Most of her prepregnancy tests were normal, except a not smooth right fallopian tube. Her G-band karyotype of peripheral blood lymphocytes was mos 46, XX, del(16)(q22)[40]/46, XX, fra(16)(q22)[29]/46, XX, fra(16)tr(16)(q22)[3]/46, XX[28] which inherited from her mother. The SCE assay detected a significantly higher frequency of SCEs in the 16q region of the patient's chromosomes compared to her mother and a healthy control. However, the average SCEs per chromosome were quite close. Moreover, copy number variation (CNV) sequencing showed no deletion nor duplication at 16q22. Conclusion: Infertility cannot be completely attributed to the fragile site on chromosome 16q22. Assisted reproductive technology combined with preimplantation genetic testing may help in achieving a healthy live birth.

5.
Plant Cell Environ ; 47(5): 1877-1894, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38343027

RESUMEN

ETHYLENE RESPONSE FACTOR 1 (ERF1) plays an important role in integrating hormone crosstalk and stress responses. Previous studies have shown that ERF1 is unstable in the dark and its degradation is mediated by UBIQUITIN-CONJUGATING ENZYME 18. However, whether there are other enzymes regulating ERF1's stability remains unclear. Here, we use various in vitro and in vivo biochemical, genetic and stress-tolerance tests to demonstrate that both CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) and SUMO-CONJUGATING ENZYME 1 (SCE1) regulate the stability of ERF1. We also performed transcriptomic analyses to understand their common regulatory pathways. We show that COP1 mediates ERF1 ubiquitination in the dark while SCE1 mediates ERF1 sumoylation in the light. ERF1 stability is positively regulated by SCE1 and negatively regulated by COP1. Upon abiotic stress, SCE1 plays a positive role in stress defence by regulating the expression of ERF1's downstream stress-responsive genes, whereas COP1 plays a negative role in stress response. Moreover, ERF1 also promotes photomorphogenesis and the expression of light-responsive genes. Our study reveals the molecular mechanism of how COP1 and SCE1 counteract to regulate ERF1's stability and light-stress signalling crosstalk.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Etilenos/metabolismo , Regulación de la Expresión Génica de las Plantas , Fotoperiodo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
6.
Int J Mol Sci ; 24(23)2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38069277

RESUMEN

S-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue distribution profiles, with a specific focus on central nervous system distribution and metabolism, of S-CE-123 and R-modafinil. To address this objective, a precise liquid chromatography-high resolution mass spectrometry method was developed and partially validated. Neuropharmacokinetic parameters were assessed using the Combinatory Mapping Approach. Our findings reveal distinct differences between the two compounds. Notably, S-CE-123 demonstrates a significantly superior extent of transport across the blood-brain barrier (BBB), with an unbound brain-to-plasma concentration ratio (Kp,uu,brain) of 0.5, compared to R-modafinil's Kp,uu,brain of 0.1. A similar pattern was observed for the transport across the blood-spinal cord barrier. Concerning the drug transport across cellular membranes, we observed that S-CE-123 primarily localizes in the brain interstitial space, whereas R-modafinil distributes more evenly across both sides of the plasma membrane of the brain's parenchymal cells (Kp,uu,cell). Furthermore, our study highlights the substantial differences in hepatic metabolic stability, with S-CE-123 having a 9.3-fold faster metabolism compared to R-modafinil. In summary, the combination of improved BBB transport and higher affinity of S-CE-123 to dopamine transporters in comparison to R-modafinil makes S-CE-123 a promising candidate for further testing for the treatment of cognitive decline.


Asunto(s)
Compuestos de Bencidrilo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Compuestos de Bencidrilo/metabolismo , Compuestos de Bencidrilo/farmacocinética , Encéfalo/metabolismo , Sistema Nervioso Central/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Modafinilo/metabolismo
7.
Plant J ; 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37840457

RESUMEN

Efficient chromatin condensation is required to transport chromosomes during mitosis and meiosis, forming daughter cells. While it is well accepted that these processes follow fundamental rules, there has been a controversial debate for more than 140 years on whether the higher-order chromatin organization in chromosomes is evolutionarily conserved. Here, we summarize historical and recent investigations based on classical and modern methods. In particular, classical light microscopy observations based on living, fixed, and treated chromosomes covering a wide range of plant and animal species, and even in single-cell eukaryotes suggest that the chromatids of large chromosomes are formed by a coiled chromatin thread, named the chromonema. More recently, these findings were confirmed by electron and super-resolution microscopy, oligo-FISH, molecular interaction data, and polymer simulation. Altogether, we describe common and divergent features of coiled chromonemata in different species. We hypothesize that chromonema coiling in large chromosomes is a fundamental feature established early during the evolution of eukaryotes to handle increasing genome sizes.

8.
Heliyon ; 9(7): e17656, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37449162

RESUMEN

This paper investigates the relationship between measures of intellectual capital efficiency and the performance of the listed banks in Bangladesh. We have collected data from the listed bank's published annual reports for seven years (2015-2021). We have primarily used standard panel data analysis techniques to assess the static relationships. In addition, to the static models, we have also checked the dynamic models for robustness in the context of Bangladesh. Following the RBV (Resource Based theory), we have found that the MVAIC (Modified Value-Added Intellectual Coefficient) significantly and positively determines firm performance in both static and dynamic methods. However, various components of MVAIC show differing relationships, which indicates that the two-step system GMM (Generalized Method of Moments) is superior to static models. The moderating role of MEETING (Company Meetings) is significant with respect to MVAIC. In addition, the moderating role of corporate governance variables at the component level remained the same in both methods. Our further analysis of the association with respect to the before and during pandemic periods suggests that the relationship remains the same irrespective of the period under study. Future research can use this paper to understand the significance of dynamic modeling while studying IC (Intellectual Capital) in an emerging economy context. This is among a few studies that have applied both static and dynamic models to assess the relationship between IC and firm performance in the context of emerging economies. Policymakers and bank managers in Bangladesh could use the findings of this study to realize that IC is much more valuable than other available tangible assets in creating a sustainable competitive advantage.

9.
Animals (Basel) ; 13(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36766399

RESUMEN

There are extensive studies on chromosome morphology and karyotype diversity in primates, yet we still lack insight into genomic instability as a key factor underlying the enormous interspecies chromosomal variability and its potential contribution to evolutionary dynamics. In this sense, the assessment of spontaneous sister chromatid exchange (SCE) frequencies represents a powerful tool for evaluating genome stability. Here, we employed G-banding, fluorescence plus Giemsa (FPG), and chromosome orientation fluorescence in situ hybridization (CO-FISH) methodologies to characterize both chromosome-specific frequencies of spontaneously occurring SCE throughout the genome (G-SCE) and telomere-specific SCE (T-SCE). We analyzed primary fibroblast cultures from two male species of Ateles living in captivity: Ateles paniscus (APA) and Ateles chamek (ACH). High frequencies of G-SCEs were observed in both species. Interestingly, G-SCEs clustered on evolutionary relevant chromosome pairs: ACH chromosomes 1, 2, 3, 4, and 7, and APA chromosomes 1, 2, 3, 4/12, 7, and 10. Furthermore, a statistically significant difference between the observed and expected G-SCE frequencies, not correlated with chromosome size, was also detected. CO-FISH analyses revealed the presence of telomere-specific recombination events in both species, which included T-SCE, as well as interstitial telomere signals and telomere duplications, with APA chromosomes displaying higher frequencies, compared to ACH. Our analyses support the hypothesis that regions of Ateles chromosomes susceptible to recombination events are fragile sites and evolutionary hot spots. Thus, we propose SCE analyses as a valuable indicator of genome instability in non-human primates.

10.
J Trace Elem Med Biol ; 69: 126894, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34749035

RESUMEN

BACKGROUND: Safe exposure levels for industrial chemicals are a prerequisite to the safety of workers in occupational settings. METHODS: The application areas of the benchmark dose (BMD) approach have tremendously increased in recent years. Quantitative analyzes of dose-response relationships of genotoxic chemicals are among these application areas too. This study investigates the applicability of sister chromatid exchange (SCE) frequencies in lymphocytes of lead-exposed workers to derive a biological limit value (BLV) for inorganic lead. To this end, our previously published occupational lead exposure data were pooled and re-examined by using the BMD approach. Subsequently, we determined the point of departure (POD) value for lead-induced SCE frequencies in lymphocytes. Accordingly, the blood lead concentrations and SCE frequencies in lymphocytes of 26 control and 108 lead-exposed male voluntary workers employed in a battery manufacturing plant were subjected to BMD modeling to determine the BMD confidence interval (BMD-CI). RESULTS: According to our data set, benchmark dose lower bound (BMDL) of 6.55 µg Pb/dL blood for the SCE frequencies in lymphocytes of lead-exposed workers has been obtained. CONCLUSION: The blood lead concentration of 6.55 µg/dL might be proposed as the BLV for lead and its inorganic lead compounds based on our dataset.


Asunto(s)
Plomo , Exposición Profesional , Benchmarking , Daño del ADN , Humanos , Plomo/toxicidad , Linfocitos , Masculino , Exposición Profesional/efectos adversos , Intercambio de Cromátides Hermanas
11.
Recent Pat Nanotechnol ; 16(4): 326-332, 2022 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-34825645

RESUMEN

With the continuous miniaturization in device dimension to reach the expectation raised by semiconductor users, the shape and size of the MOSFET are changing periodically. The journey started in the year 1960, reached the milestone, and still going on to create history. Due to continuous downscaling, the device dimensions have already reached the critical limit and further miniaturization is a challenge. As a result of which some unwanted effects were raised unknowingly to suppress the device performances while entering into nanoscale. To overcome these kinds of barriers, different device architectures were proposed to keep the journey on. This paper focused on those types of advanced structures in MOSFET, which kept Moore's law alive.


Asunto(s)
Semiconductores , Diseño de Equipo , Miniaturización
12.
Front Hum Neurosci ; 15: 750964, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34671249

RESUMEN

Numbers are mapped onto space from birth on, as evidenced by a variety of interactions between the processing of numerical and spatial information. In particular, larger numbers are associated to larger spatial extents (number/spatial extent mapping) and to rightward spatial locations (number/location mapping), and smaller numbers are associated to smaller spatial extents and leftward spatial locations. These two main types of number/space mappings (number/spatial extent and number/location mappings) are usually assumed to reflect the fact that numbers are represented on an internal continuum: the mental number line. However, to date there is very little evidence that these two mappings actually reflect a single representational object. Across two experiments in adults, we investigated the interaction between number/location and number/spatial extent congruency effects, both when numbers were presented in a non-symbolic and in a symbolic format. We observed a significant interaction between the two mappings, but only in the context of an implicit numerical task. The results were unaffected by the format of presentation of numbers. We conclude that the number/location and the number/spatial extent mappings can stem from the activation of a single representational object, but only in specific experimental contexts.

13.
Eur J Radiol Open ; 8: 100378, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34632000

RESUMEN

BACKGROUND: Grade of brain tumor is thought to be the most significant and crucial component in treatment management. Recent development in medical imaging techniques have led to the introduce non-invasive methods for brain tumor grading such as different magnetic resonance imaging (MRI) protocols. Combination of different MRI protocols with fusion algorithms for tumor grading is used to increase diagnostic improvement. This paper investigated the efficiency of the Laplacian Re-decomposition (LRD) fusion algorithms for glioma grading. PROCEDURES: In this study, 69 patients were examined with MRI. The T1 post enhancement (T1Gd) and diffusion-weighted images (DWI) were obtained. To evaluated LRD performance for glioma grading, we compared the parameters of the receiver operating characteristic (ROC) curves. FINDINGS: We found that the average Relative Signal Contrast (RSC) for high-grade gliomas is greater than RSCs for low-grade gliomas in T1Gd images and all fused images. No significant difference in RSCs of DWI images was observed between low-grade and high-grade gliomas. However, a significant RSCs difference was detected between grade III and IV in the T1Gd, b50, and all fussed images. CONCLUSIONS: This research suggests that T1Gd images are an appropriate imaging protocol for separating low-grade and high-grade gliomas. According to the findings of this study, we may use the LRD fusion algorithm to increase the diagnostic value of T1Gd and DWI picture for grades III and IV glioma distinction. In conclusion, this article has emphasized the significance of the LRD fusion algorithm as a tool for differentiating grade III and IV gliomas.

14.
Mol Cell ; 81(14): 2989-3006.e9, 2021 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-34197737

RESUMEN

Stalled DNA replication fork restart after stress as orchestrated by ATR kinase, BLM helicase, and structure-specific nucleases enables replication, cell survival, and genome stability. Here we unveil human exonuclease V (EXO5) as an ATR-regulated DNA structure-specific nuclease and BLM partner for replication fork restart. We find that elevated EXO5 in tumors correlates with increased mutation loads and poor patient survival, suggesting that EXO5 upregulation has oncogenic potential. Structural, mechanistic, and mutational analyses of EXO5 and EXO5-DNA complexes reveal a single-stranded DNA binding channel with an adjacent ATR phosphorylation motif (T88Q89) that regulates EXO5 nuclease activity and BLM binding identified by mass spectrometric analysis. EXO5 phospho-mimetic mutant rescues the restart defect from EXO5 depletion that decreases fork progression, DNA damage repair, and cell survival. EXO5 depletion furthermore rescues survival of FANCA-deficient cells and indicates EXO5 functions epistatically with SMARCAL1 and BLM. Thus, an EXO5 axis connects ATR and BLM in directing replication fork restart.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/genética , Replicación del ADN/genética , ADN/genética , Exonucleasas/genética , Inestabilidad Genómica/genética , RecQ Helicasas/genética , Línea Celular , Línea Celular Tumoral , Daño del ADN/genética , ADN Helicasas/genética , Análisis Mutacional de ADN/métodos , Reparación del ADN/genética , Proteínas de Unión al ADN/genética , Células HEK293 , Células HeLa , Humanos , Mutación/genética , Oncogenes/genética , Fosforilación/genética , Regulación hacia Arriba/genética
15.
Comput Struct Biotechnol J ; 19: 1874-1888, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33995893

RESUMEN

Globin-coupled sensors (GCS) usually consist of three domains: a sensor/globin, a linker, and a transmitter domain. The globin domain (GD), activated by ligand binding and/or redox change, induces an intramolecular signal transduction resulting in a response of the transmitter domain. Depending on the nature of the transmitter domain, GCSs can have different activities and functions, including adenylate and di-guanylate cyclase, histidine kinase activity, aerotaxis and/or oxygen sensing function. The gram-negative delta-proteobacterium Geobacter sulfurreducens expresses a protein with a GD covalently linked to a four transmembrane domain, classified, by sequence similarity, as GCS (GsGCS). While its GD is fully characterized, not so its transmembrane domain, which is rarely found in the globin superfamily. In the present work, GsGCS was characterized spectroscopically and by native ion mobility-mass spectrometry in combination with cryo-electron microscopy. Although lacking high resolution, the oligomeric state and the electron density map were valuable for further rational modeling of the full-length GsGCS structure. This model demonstrates that GsGCS forms a transmembrane domain-driven tetramer with minimal contact between the GDs and with the heme groups oriented outward. This organization makes an intramolecular signal transduction less likely. Our results, including the auto-oxidation rate and redox potential, suggest a potential role for GsGCS as redox sensor or in a membrane-bound e-/H+ transfer. As such, GsGCS might act as a player in connecting energy production to the oxidation of organic compounds and metal reduction. Database searches indicate that GDs linked to a four or seven helices transmembrane domain occur more frequently than expected.

16.
Life Sci ; 277: 119556, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-33945829

RESUMEN

OBJECTIVE: Poly(ADP-ribose) polymerase1 (PARP1) interacts and poly(ADP-ribosyl)ates telomere repeat binding factor 2 (TRF2), which acts as a platform to recruit a large number of proteins at the telomere. Since the discovery of TRF2-SLX4 interaction, SLX4 is becoming the key player in telomere length (TL) maintenance and repair by telomere sister chromatid exchange (T-SCE). Defective TL maintenance pathway results in a spectrum of diseases called telomeropathies like dyskeratosis congenita, aplastic anemia, fanconi anemia, cancer. We aimed to study the role of SLX4 and PARP1 on each other's telomere localization, T-SCE, and TL maintenance in human telomerase-negative osteosarcoma U2OS cells to understand some of the molecular mechanisms of telomere homeostasis. MATERIALS AND METHODS: We checked the role of SLX4 and PARP1 on each other's telomere localization by telomere immunofluorescence. We have cloned full-length wild-type and catalytically inactive mutant PARP1 to understand the role of poly(ADP-ribosyl)ation reaction by PARP1 in telomere length homeostasis. TL of U2OS cells was measured by Q-FISH. T-SCE was measured by Telomere-FISH. KEY FINDINGS: We observed that SLX4 has no role in the telomere localization of PARP1. However, reduced localization of SLX4 at undamaged and damaged telomere upon PARP1 depletion was reversed by overexpression of exogenous wild-type PARP1 but not by overexpression of catalytically inactive mutant PARP1. PARP1 depletion synergized SLX4 depletion-mediated reduction of T-SCE. Furthermore, SLX4 depletion elongated TL, and combined insufficiency of SLX4 with PARP1 further elongated TL. CONCLUSION: So, PARP1 controls SLX4 recruitment at telomere by poly(ADP-ribosyl)ation reaction, thereby regulating SLX4-mediated T-SCE and TL homeostasis.


Asunto(s)
Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Recombinasas/metabolismo , Intercambio de Cromátides Hermanas/fisiología , Línea Celular Tumoral , Cromátides/metabolismo , Cromátides/fisiología , Reparación del ADN , Homeostasis , Humanos , Poli(ADP-Ribosa) Polimerasa-1/fisiología , Poli(ADP-Ribosa) Polimerasas/genética , Recombinasas/genética , Recombinasas/fisiología , Telomerasa/metabolismo , Telómero/fisiología , Homeostasis del Telómero/fisiología , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismo
17.
Accid Anal Prev ; 157: 106185, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34015605

RESUMEN

Advancements in data collection and processing methods have produced large databases containing high quality vehicular data. Despite this, conventional vehicle-vehicle collisions remain difficult to identify due to their rarity. Therefore, there is a need to identify potential collisions given the introduction of these new data collection methods. Surrogate indicators are a popular methods utilised to identify such events, however, the type of surrogate that can be used depends heavily on the type of data collection method. Though most surrogate indicators are used at different road geometries, there is evidence to suggest that some surrogate indicators may perform better than others at a given geometry. This review provides two key contributions to the body of literature. Firstly, a review of kinematic surrogates is put forward, along with a discussion on the whether these surrogates can be contextualised at different road geometries. Secondly, an extensive analysis and discussion of observer-based and video processed surrogate indicators, the collision types they aim to identify and the geometries they have been used at previously were analysed and advantages and disadvantages of the surrogates have been presented for future use. To do this, intersections, highways and roundabouts were selected and divided into geometry subtypes (i.e. three-legged and four-legged intersection) and segments (i.e. approaches to intersections and internal to the intersection) based on the likelihood of crash types and pre-crash manoeuvres occurring in that segment. Due to the lack of research around the use of kinematic triggers at road geometries, it is difficult to advocate for the use of any given trigger over another at a given geometry. Furthermore, it was found that kinematic triggers cannot accurately identify conflicts from naturalistic driving data and require the use of advanced statistical techniques such as machine learning to increase accuracy. A brief analysis of threshold identification techniques was also performed. Several future works have been put forward including the introduction of surrogates which capture conflict severity and the role of surrogate indicators in connected and automated vehicle environments.


Asunto(s)
Accidentes de Tránsito , Conducción de Automóvil , Recolección de Datos , Bases de Datos Factuales , Humanos , Probabilidad
18.
Int J Pharm X ; 3: 100077, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33870182

RESUMEN

Despite significant advances in the research domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent mitigation of the impact of this variability on the manufacturing process and drug product was recently stressed in the Draft Guidance for Industry on Quality Considerations for Continuous Manufacturing by the U.S. Food and Drug Administration (FDA). Therefore, this study assessed the impact of microcrystalline cellulose (MCC) batch-to-batch variability and process settings in a continuous twin screw wet granulation and semi-continuous drying line. Based on extensive raw material characterization and subsequent principal component analysis, raw material variability was quantitatively introduced in the design of experiments approach by means of t1 and t2 scores. L/S ratio had a larger effect on critical granule attributes and processability than screw speed and drying time. A large impact of the t1 and t2 scores was found, indicating the importance of raw material attributes. For the studied formulation, it was concluded that MCC batches with a low water binding capacity, low moisture content and high bulk density generated granules with the most desirable quality attributes. Additionally, an innovative and quantitative approach towards mitigating batch-to-batch variability of raw materials was proposed, which is also applicable for additional excipients and APIs.

19.
Curr Biol ; 31(7): 1499-1507.e3, 2021 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-33740426

RESUMEN

Sexual reproduction shuffles the parental genomes to generate new genetic combinations. To achieve that, the genome is subjected to numerous double-strand breaks, the repair of which involves two crucial decisions: repair pathway and repair template.1 Use of crossover pathways with the homologous chromosome as template exchanges genetic information and directs chromosome segregation. Crossover repair, however, can compromise the integrity of the repair template and is therefore tightly regulated. The extent to which crossover pathways are used during sister-directed repair is unclear because the identical sister chromatids are difficult to distinguish. Nonetheless, indirect assays have led to the suggestion that inter-sister crossovers, or sister chromatid exchanges (SCEs), are quite common.2-11 Here we devised a technique to directly score physiological SCEs in the C. elegans germline using selective sister chromatid labeling with the thymidine analog 5-ethynyl-2'-deoxyuridine (EdU). Surprisingly, we find SCEs to be rare in meiosis, accounting for <2% of repair events. SCEs remain rare even when the homologous chromosome is unavailable, indicating that almost all sister-directed repair is channeled into noncrossover pathways. We identify two mechanisms that limit SCEs. First, SCEs are elevated in the absence of the RecQ helicase BLMHIM-6. Second, the synaptonemal complex-a conserved interface that promotes crossover repair12,13-promotes SCEs when localized between the sisters. Our data suggest that crossover pathways in C. elegans are only used to generate the single necessary link between the homologous chromosomes. Noncrossover pathways repair almost all other breaks, regardless of the repair template.


Asunto(s)
Caenorhabditis elegans , Meiosis , Intercambio de Cromátides Hermanas , Animales , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans , Cromátides/genética , Roturas del ADN de Doble Cadena , Reparación del ADN
20.
Neuroimage ; 232: 117892, 2021 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-33617992

RESUMEN

The brain and the spinal cord together make up the central nervous system (CNS). The functions of the human brain have been the focus of neuroscience research for a long time. However, the spinal cord is largely ignored, and the functional interaction of these two parts of the CNS is only partly understood. This study developed a novel method to simultaneously record spinal cord electrophysiology (SCE) and electroencephalography (EEG) signals and validated its performance using a classical resting-state study design with two experimental conditions: eyes-closed (EC) and eyes-open (EO). We recruited nine postherpetic neuralgia patients implanted with a spinal cord stimulator, which was modified to record SCE signals simultaneously with EEG signals. For both EEG and SCE, similar differences were found in delta- and alpha-band oscillations between the EC and EO conditions, and the spectral power of these frequency bands was able to predict EC/EO behaviors. Moreover, causal connectivity analysis suggested a top-down regulation in delta-band oscillations from the brain to the spinal cord. Altogether, this study demonstrates the validity of simultaneous SCE-EEG recording and shows that the novel method is a valuable tool to investigate the brain-spinal interaction. With this method, we can better unite knowledge about the brain and the spinal cord for a deeper understanding of the functions of the whole CNS.


Asunto(s)
Encéfalo/fisiología , Electroencefalografía/métodos , Fenómenos Electrofisiológicos/fisiología , Neuralgia Posherpética/fisiopatología , Médula Espinal/fisiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuralgia Posherpética/diagnóstico
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