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Studies1,2 have shown that the remnants of destroyed planets and debris-disk planetesimals can survive the volatile evolution of their host stars into white dwarfs3,4, but few intact planetary bodies around white dwarfs have been detected5-8. Simulations predict9-11 that planets in Jupiter-like orbits around stars of â²8 Mâ (solar mass) avoid being destroyed by the strong tidal forces of their stellar host, but as yet, there has been no observational confirmation of such a survivor. Here we report the non-detection of a main-sequence lens star in the microlensing event MOA-2010-BLG-477Lb12 using near-infrared observations from the Keck Observatory. We determine that this system contains a 0.53 ± 0.11 Mâ white-dwarf host orbited by a 1.4 ± 0.3 Jupiter-mass planet with a separation on the plane of the sky of 2.8 ± 0.5 astronomical units, which implies a semi-major axis larger than this. This system is evidence that planets around white dwarfs can survive the giant and asymptotic giant phases of their host's evolution, and supports the prediction that more than half of white dwarfs have Jovian planetary companions13. Located at approximately 2.0 kiloparsecs towards the centre of our Galaxy, it is likely to represent an analogue to the end stages of the Sun and Jupiter in our own Solar System.
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BACKGROUND: Numerous transcriptomic-based models have been developed to predict or understand the fundamental mechanisms driving biological phenotypes. However, few models have successfully transitioned into clinical practice due to challenges associated with generalizability and interpretability. To address these issues, researchers have turned to dimensionality reduction methods and have begun implementing transfer learning approaches. METHODS: In this study, we aimed to determine the optimal combination of dimensionality reduction and regularization methods for predictive modeling. We applied seven dimensionality reduction methods to various datasets, including two supervised methods (linear optimal low-rank projection and low-rank canonical correlation analysis), two unsupervised methods [principal component analysis and consensus independent component analysis (c-ICA)], and three methods [autoencoder (AE), adversarial variational autoencoder, and c-ICA] within a transfer learning framework, trained on > 140,000 transcriptomic profiles. To assess the performance of the different combinations, we used a cross-validation setup encapsulated within a permutation testing framework, analyzing 30 different transcriptomic datasets with binary phenotypes. Furthermore, we included datasets with small sample sizes and phenotypes of varying degrees of predictability, and we employed independent datasets for validation. RESULTS: Our findings revealed that regularized models without dimensionality reduction achieved the highest predictive performance, challenging the necessity of dimensionality reduction when the primary goal is to achieve optimal predictive performance. However, models using AE and c-ICA with transfer learning for dimensionality reduction showed comparable performance, with enhanced interpretability and robustness of predictors, compared to models using non-dimensionality-reduced data. CONCLUSION: These findings offer valuable insights into the optimal combination of strategies for enhancing the predictive performance, interpretability, and generalizability of transcriptomic-based models.
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Fenotipo , Transcriptoma , Transcriptoma/genética , Humanos , Perfilación de la Expresión Génica/métodos , Aprendizaje Automático , Biología Computacional/métodos , Algoritmos , Análisis de Componente PrincipalRESUMEN
Discovering causal influences among internal variables is a fundamental goal of complex systems research. This paper presents a framework for uncovering hidden relationships from limited time-series data by combining methods from nonlinear estimation and information theory. The approach is based on two sequential steps: first, we reconstruct a more complete state of the underlying dynamical system, and second, we calculate mutual information between pairs of internal state variables to detail causal dependencies. Equipped with time-series data related to the spread of COVID-19 from the past three years, we apply this approach to identify the drivers of falling and rising infections during the three main waves of infection in the Chicago metropolitan region. The unscented Kalman filter nonlinear estimation algorithm is implemented on an established epidemiological model of COVID-19, which we refine to include isolation, masking, loss of immunity, and stochastic transition rates. Through the systematic study of mutual information between infection rate and various stochastic parameters, we find that increased mobility, decreased mask use, and loss of immunity post sickness played a key role in rising infections, while falling infections were controlled by masking and isolation.
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COVID-19 , Dinámicas no Lineales , Humanos , Simulación por Computador , COVID-19/epidemiología , AlgoritmosRESUMEN
Workers, particularly outdoor workers, are among the populations most disproportionately affected by climate-related hazards. However, scientific research and control actions to comprehensively address these hazards are notably absent. To assess this absence, a seven-category framework was developed in 2009 to characterize the scientific literature published from 1988-2008. Using this framework, a second assessment examined the literature published through 2014, and the current one examines literature from 2014-2021. The objectives were to present literature that updates the framework and related topics and increases awareness of the role of climate change in occupational safety and health. In general, there is substantial literature on worker hazards related to ambient temperatures, biological hazards, and extreme weather but less on air pollution, ultraviolet radiation, industrial transitions, and the built environment. There is growing literature on mental health and health equity issues related to climate change, but much more research is needed. The socioeconomic impacts of climate change also require more research. This study illustrates that workers are experiencing increased morbidity and mortality related to climate change. In all areas of climate-related worker risk, including geoengineering, research is needed on the causality and prevalence of hazards, along with surveillance to identify, and interventions for hazard prevention and control.
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Exposición Profesional , Salud Laboral , Humanos , Cambio Climático , Rayos Ultravioleta/efectos adversos , Exposición Profesional/análisisRESUMEN
The present investigation aimed to evaluate antibacterial, antifungal and antioxidant efficacy of essential oils of three commonly used spices (black pepper, cinnamon and clove) in combination along with chemical characterization and toxicity evaluation. Among the possible combinations tested, cinnamon/clove oil combination showed synergistic antibacterial activity against foodborne bacteria Staphylococcus aureus, Listeria monocytogenes, Salmonella typhimurium and Pseudomonas aeruginosa and synergistic antifungal activity against Aspergillus niger as well as synergistic antioxidant potential in DPPH radical scavenging model system. GC-HRMS analysis revealed that out of thirteen identified components from clove oil, eugenol was found to be the main constituent of the oil; whereas out of twenty one identified constituents from cinnamon oil, the main component was cinnamaldehyde. Cinnamon/clove oil combination did not show any cytotoxic potential at recommended dosage level (IC50 > 2000 µg/ml). The results provide evidence that cinnamon/clove oil combination might indeed be used as a potential source of safe and effective novel natural antibacterial, antifungal and antioxidant blend in the food and pharmaceutical industries. To the best of our knowledge, this is the first time a combination of essential oils has been tested as natural preservatives to prevent both microbial proliferation and oxidative deterioration at sufficiently low concentrations.
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Antibacterianos/farmacología , Antifúngicos/farmacología , Antioxidantes/farmacología , Aceite de Clavo/farmacología , Sinergismo Farmacológico , Aceites Volátiles/farmacología , Acroleína/análogos & derivados , Acroleína/farmacología , Aspergillus niger/efectos de los fármacos , Cinnamomum zeylanicum/química , Aceite de Clavo/química , Eugenol/farmacología , Listeria monocytogenes/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Piper nigrum/química , Pseudomonas aeruginosa/efectos de los fármacos , Salmonella typhimurium/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Syzygium/químicaRESUMEN
The aim of this study was to examine whether the process of initial colonization and the formation of mature biofilm structure of foodborne bacterial pathogens Listeria monocytogenes and Salmonella typhimurium can be impeded by active essential oil components ß-caryophyllene, cinnamaldehyde and eugenol at their individual and combined effects. Among the essential oil components tested, cinnamaldehyde and eugenol at their individual effect showed >50% degradation in biofilm biomass against preformed (matured) biofilms of both the studied bacteria, whereas ß-caryophyllene failed to do so. In combination, cinnamaldehyde/eugenol blend showed synergistic antibiofilm efficacy against preformed biofilms of both the studied bacteria L. monocytogenes (FICI: 0·24) and S. typhimurium (FICI: 0·40), whereas other tested combinations showed additive antibiofilm efficacy with FICI ranged from 2·02 to 2·35. Essential oil components alone and in combination also showed much higher inhibition effect on biofilm formation at the initial stage compared to their inhibition effect on preformed biofilms. The results provide evidence that cinnamaldehyde/eugenol combination may help in designing a more potent novel, natural antibiofilm blend at sufficiently low concentrations in the food and pharmaceutical industries. SIGNIFICANCE AND IMPACT OF THE STUDY: In the present work, synergistic antibiofilm efficacy of cinnamaldehyde/eugenol combination against established biofilms of foodborne bacterial pathogens Listeria monocytogenes and Salmonella typhimurium has been reported. These synergistic interactions may help in designing a more potent, safe and effective novel natural antibiofilm agent in food and pharmaceutical industries. Besides, this combination will also be helpful in reducing concentration of individual components, thereby minimizing the undesirable impact on sensory properties of food. To our knowledge, this is the first time, synergistic antibiofilm efficacy of cinnamaldehyde/eugenol blend against established biofilms of foodborne bacterial pathogens has been reported.
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Acroleína/análogos & derivados , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Listeria monocytogenes/efectos de los fármacos , Sesquiterpenos Policíclicos/farmacología , Salmonella typhimurium/efectos de los fármacos , Acroleína/farmacología , Eugenol/farmacología , Listeria monocytogenes/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/farmacología , Salmonella typhimurium/crecimiento & desarrolloRESUMEN
BACKGROUND: There is a paucity of studies examining the beneficial effects of fish consumption on cardiovascular diseases (CVDs) among adults with diabetes, who experience a substantially high risk of CVDs. METHODS AND RESULTS: We analyzed the data of 1136 adults with diabetes mellitus aged 18 years and older who participated in the National Health and Nutrition Examination Survey, 1988-1994, and were followed up through December 31, 2010. We used Cox regression to estimate the adjusted hazard ratios (HRs) for the relative risk across the levels of fish consumption. A total of 698 deaths were recorded at the end of 11,465 person-years follow-up with a mortality rate of 60.88 per 1000 person-years. CVDs were listed as a contributing cause for 326 deaths, thus accounting for 46.4% of total deaths. Stroke-specific mortality rate among patients who ate fish less than once a week was more than twice as high as that among patients who ate fish more than twice a week, 6.23 vs. 2.36 per 1000 person-years, respectively. The corresponding CVD-specific rate was 34.38 vs. 22.99 per 1000 person-years, respectively. The adjusted HRs of death due to stroke were 1.00 (reference), 0.55 (95% confidence interval = 0.28-1.07), and 0.30 (0.11-0.80) among patients who ate fish <1, 1-2, and 2 + times a week, and the corresponding HRs of death due to CVDs were 1.00 (reference), 0.78 (0.60-1.02), and 0.69 (0.50-0.96), respectively. CONCLUSIONS: A high consumption of fish was associated with a low risk of death due to CVDs, especially stroke, among adults with diabetes.
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Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus/dietoterapia , Diabetes Mellitus/mortalidad , Alimentos Marinos , Enfermedades Cardiovasculares/diagnóstico , Causas de Muerte , Diabetes Mellitus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Tamaño de la Porción , Pronóstico , Factores Protectores , Ingesta Diaria Recomendada , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: To assess and compare the implementation of antimicrobial stewardship (AMS) interventions recommended within the national AMS toolkits, TARGET and Start Smart Then Focus, in English primary and secondary healthcare settings in 2014, to determine the prevalence of cross-sector engagement to drive AMS interventions and to propose next steps to improve implementation of AMS. METHODS: Electronic surveys were circulated to all 211 clinical commissioning groups (CCGs; primary sector) and to 146 (out of the 159) acute trusts (secondary sector) in England. Response rates were 39% and 63% for the primary and secondary sectors, respectively. RESULTS: The majority of CCGs and acute trusts reported reviewing national AMS toolkits formally or informally (60% and 87%, respectively). However, only 13% of CCGs and 46% of acute trusts had developed an action plan for the implementation of these toolkits. Only 5% of CCGs had antimicrobial pharmacists in post; however, the role of specialist antimicrobial pharmacists continued to remain embedded within acute trusts, with 83% of responding trusts having an antimicrobial pharmacist at a senior grade. CONCLUSIONS: The majority of healthcare organizations review national AMS toolkits; however, implementation of the toolkits, through the development of action plans to deliver AMS interventions, requires improvement. For the first time, we report the extent of cross-sector and multidisciplinary collaboration to deliver AMS interventions in both primary and secondary care sectors in England. Results highlight that further qualitative and quantitative work is required to explore mutual benefits and promote best practice. Antimicrobial pharmacists remain leaders for implementing AMS interventions across both primary and secondary healthcare sectors.
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Antiinfecciosos/uso terapéutico , Utilización de Medicamentos/normas , Política de Salud , Atención Primaria de Salud/métodos , Atención Secundaria de Salud/métodos , Estudios Transversales , Inglaterra , Adhesión a Directriz , Investigación sobre Servicios de Salud , HumanosRESUMEN
Colorectal cancer (CRC) is one of the most common solid tumors worldwide. Recent evidence suggests that a population of cancer cells, called cancer stem cells (CSCs), is responsible for tumor heterogeneity, invasion, metastasis, therapeutic resistance, and recurrence of CRC. The isolation and characterization of CSCs using cell surface markers have been reported previously with varying results. In this study, we investigated a panel of four putative CSC markers, CD44, CD24, CD166, and EpCAM, to define CRC-CSC. Paraffin embedded tissue samples from different grades of primary, untreated CRC were analyzed for the expression of four CSC markers CD44, CD326, CD24, and CD166, using immunohistochemistry. Flow cytometric analysis of CRC-CSC from HT29 (low grade) and HCT116 (high grade) human colorectal cancer cell lines was done. Marker-based isolation of CSC and non-CSC-bulk-tumor cells from HT29 was done using FACS, and tumor sphere assay was performed. There was a statistically significant difference (p < 0.05) in the expression of CD44, CD326, and CD166 between cases and controls. A novel cutoff distribution of CD44 and CD166 was suggested to help for better immunohistochemical analysis of CRC. Higher prevalence of CSC was seen in high-grade CRC as compared to low-grade CRC. Sorted and cultured CD44 + CD166+ cells formed tumor spheres, suggesting that these cells, having properties of self renewal and anchorage independent proliferation, were in fact CSC. Hence, CD44 and CD166 may serve as good CRC-CSC markers when used together with novel cutoff immunohistochemistry (IHC) expression levels.
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Adenocarcinoma/secundario , Antígenos CD/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Células Madre Neoplásicas/patología , Adenocarcinoma/metabolismo , Adulto , Antígeno CD24/metabolismo , Moléculas de Adhesión Celular Neuronal/metabolismo , Neoplasias Colorrectales/metabolismo , Molécula de Adhesión Celular Epitelial/metabolismo , Femenino , Proteínas Fetales/metabolismo , Citometría de Flujo , Humanos , Receptores de Hialuranos/metabolismo , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Células Madre Neoplásicas/metabolismo , Pronóstico , Células Tumorales CultivadasRESUMEN
In 2009, a preliminary framework for how climate change could affect worker safety and health was described. That framework was based on a literature search from 1988-2008 that supported seven categories of climate-related occupational hazards: (1) increased ambient temperature; (2) air pollution; (3) ultraviolet radiation exposure; (4) extreme weather; (5) vector-borne diseases and expanded habitats; (6) industrial transitions and emerging industries; and (7) changes in the built environment. This article reviews the published literature from 2008-2014 in each of the seven categories. Additionally, three new topics related to occupational safety and health are considered: mental health effects, economic burden, and potential worker safety and health impacts associated with the nascent field of climate intervention (geoengineering). Beyond updating the literature, this article also identifies key priorities for action to better characterize and understand how occupational safety and health may be associated with climate change events and ensure that worker health and safety issues are anticipated, recognized, evaluated, and mitigated. These key priorities include research, surveillance, risk assessment, risk management, and policy development. Strong evidence indicates that climate change will continue to present occupational safety and health hazards, and this framework may be a useful tool for preventing adverse effects to workers.
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Cambio Climático , Exposición Profesional/análisis , Salud Laboral/tendencias , Temperatura , Geografía , Humanos , Medición de Riesgo , Estados UnidosRESUMEN
The A(n+1)B(n)O(3n+1) Ruddlesden-Popper homologous series offers a wide variety of functionalities including dielectric, ferroelectric, magnetic and catalytic properties. Unfortunately, the synthesis of such layered oxides has been a major challenge owing to the occurrence of growth defects that result in poor materials behaviour in the higher-order members. To understand the fundamental physics of layered oxide growth, we have developed an oxide molecular beam epitaxy system with in situ synchrotron X-ray scattering capability. We present results demonstrating that layered oxide films can dynamically rearrange during growth, leading to structures that are highly unexpected on the basis of the intended layer sequencing. Theoretical calculations indicate that rearrangement can occur in many layered oxide systems and suggest a general approach that may be essential for the construction of metastable Ruddlesden-Popper phases. We demonstrate the utility of the new-found growth strategy by performing the first atomically controlled synthesis of single-crystalline La3Ni2O7.
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We have studied the optical properties of four (LaNiO3)n/(LaMnO3)2 superlattices (SL) (n=2,3,4,5) on SrTiO3 substrates. We have measured the reflectivity at temperatures from 20 to 400 K, and extracted the optical conductivity through a fitting procedure based on a Kramers-Kronig consistent Lorentz-Drude model. With increasing LaNiO3 thickness, the SLs undergo an insulator-to-metal transition (IMT) that is accompanied by the transfer of spectral weight from high to low frequency. The presence of a broad midinfrared band, however, shows that the optical conductivity of the (LaNiO3)n/(LaMnO3)2 SLs is not a linear combination of the LaMnO_{3} and LaNiO3 conductivities. Our observations suggest that interfacial charge transfer leads to an IMT due to a change in valence at the Mn and Ni sites.
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This cross-sectional study was done to find and investigate the utilization pattern of iron chelating agents among 73 transfusion-dependent thalassaemia major patients with continuous enrolment for at least 1 year in a day care treatment centre run by The Thalassaemia Society of India, Kolkata from November 2014 to January 2015. Transfusion dependent thalassaemia major patients above the age of 2 years managed by various haematologists and Thalassaemia specialists were studied. The administration of iron chelators namely Desferrioxamine (DFO), Deferiprone (DFP) and Deferasirox (DFX) were evaluated. Forty seven (64%) of the thalassaemics had serum ferritin level below 2500 ng/dl, of whom 20(27%) patients have ferritin level below 1000ng/dl. A number of 55(75%) of 73 patients who were treated with a single chelating agent consisted 50 patients only on DFX. Exact 8(67%) patients were on DFO+DFP and 4(33%) are treated with DFX+DFP. The mean age was 19 and mean serum ferritin level was 2280 ng/dl among the thalassaemia major patients. DFX was used 68% of patients as monotherapy and 5% patients in combination therapy with DFP. DFX in the dose of 30-40 mg/kg/day was prescribed in 52% of patients. Mean dose of 15 mg/kg/day of DFX was been administered in combination with DFP (75 mg/kg/day) in 5% patients. DFO+DFP were preferred by 8 patients, out of which 6 were aged above 25. Cost of monotherapy is twice that of combination therapy. These data demonstrates the ferritin status and present scenario of utilization of chelating agents among thalassaemia major patients on repeated transfusions. The dosing of new drug, Deferasirox and the cost analysis of various chelating regimen has also been dealt. Individualization rather than rationalization of chelation therapy should be focussed upon in managing iron overload in thalassaemia.
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Transfusión Sanguínea , Quelantes del Hierro/uso terapéutico , Talasemia beta/terapia , Adolescente , Adulto , Estudios Transversales , Femenino , Ferritinas/sangre , Humanos , Masculino , Reacción a la Transfusión , Adulto Joven , Talasemia beta/sangreRESUMEN
This study evaluates cellular damage, metabolite profiling, and defence-related gene expression in tomato plants and soil microflora during Fusarium wilt disease after treatment with B. tequilensis PBE-1. Histochemical analysis showed that PBE-1 was the primary line of defence through lignin deposition and reduced cell damage. GC-MS revealed that PBE-1 treatment ameliorated stress caused by F. oxysporum infection. PBE-1 also improved transpiration, photosynthesis, and stomatal conductance in tomato. qRT-PCR suggested that the defence-related genes FLS2, SERK, NOS, WRKYT, NHO, SAUR, and MYC2, which spread infection, were highly upregulated during F. oxysporum infection, but either downregulated or expressed normally in PBE-1 + P treated plants. This indicates that the plant not only perceives the bio-control agent as a non-pathogen entity but its presence in normal metabolism and gene expression within the host plant is maintained. The study further corroborated findings that application of PBE-1 does not cause ecological disturbances in the rhizosphere. Activity of soil microflora across four treatments, measured by Average Well Colour Development (AWCD), showed continuous increases from weeks 1 to 4 post-pathogen infection, with distinct substrate usage patterns like tannic and fumaric acids impacting microbial energy source utilization and diversity. Principal Component Analysis (PCA) and diversity indices like McIntosh, Shannon, and Simpson further illustrated significant microbial community shifts over the study period. In conclusion, our findings demonstrate that B. tequilensis PBE-1 is an ideal bio-agent for field application during Fusarium wilt disease management in tomato.
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Bacillus , Fusarium , Enfermedades de las Plantas , Microbiología del Suelo , Solanum lycopersicum , Fusarium/fisiología , Fusarium/patogenicidad , Solanum lycopersicum/microbiología , Solanum lycopersicum/metabolismo , Enfermedades de las Plantas/microbiología , Bacillus/fisiología , Bacillus/metabolismo , Regulación de la Expresión Génica de las Plantas , Rizosfera , FotosíntesisRESUMEN
In this study, neural networks and support vector regression (SVR) were employed to predict the degradation over three pharmaceutically active compounds (PhACs): Ibuprofen (IBP), diclofenac (DCF), and caffeine (CAF) within a stirred reactor featuring a flotation cell with two non-concentric ultraviolet lamps. A total of 438 datapoints were collected from published works and distributed into 70% training and 30% test datasets while cross-validation was utilized to assess the training reliability. The models incorporated 15 input variables concerning reaction kinetics, molecular properties, hydrodynamic information, presence of radiation, and catalytic properties. It was observed that the Support Vector Regression (SVR) presented a poor performance as the ε hyperparameter ignored large error over low concentration levels. Meanwhile, the Artificial Neural Networks (ANN) model was able to provide rough estimations on the expected degradation of the pollutants without requiring information regarding reaction rate constants. The multi-objective optimization analysis suggested a leading role due to ozone kinetic for a rapid degradation of the contaminants and most of the results required intensification with hydrogen peroxide and Fenton process. Although both models were affected by accuracy limitations, this work provided a lightweight model to evaluate different Advanced Oxidation Processes (AOPs) by providing general information regarding the process operational conditions as well as know molecular and catalytic properties.
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Diclofenaco , Peróxido de Hidrógeno , Ibuprofeno , Aprendizaje Automático , Redes Neurales de la Computación , Diclofenaco/química , Peróxido de Hidrógeno/química , Ibuprofeno/química , Cinética , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Cafeína/química , Oxidación-Reducción , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/análisis , Ozono/química , Máquina de Vectores de Soporte , Análisis Costo-Beneficio , Rayos Ultravioleta , Catálisis , FotólisisRESUMEN
Transmission Electron Microscopy is used as a quantitative method to measure the shapes, sizes and volumes of gold nanoparticles created at a polymeric surface by three different in situ synthesis methods. The atomic number contrast (Z-contrast) imaging technique reveals nanoparticles which are formed on the surface of the polymer. However, with certain reducing agents, the gold nanoparticles are additionally found up to 20 nm below the polymer surface. In addition, plan-view high-angle annular dark-field scanning transmission electron microscopy images were statistically analyzed on one sample to measure the volume, height and effective diameter of the gold nanoparticles and their size distributions. Depth analysis from high-angle annular dark-field scanning transmission electron microscopy micrographs also gives information on the dominant shape of the nanoparticles.
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BACKGROUND: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology. METHODS: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (< CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel. RESULTS: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between < CIN2 and CIN3+ for all markers (p < 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p < 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation> 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified. CONCLUSION: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/genética , Displasia del Cuello del Útero/genética , Metilación de ADN , Detección Precoz del Cáncer/métodos , Triaje/métodos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/genética , Papillomaviridae/genética , Proteínas de Microfilamentos/genéticaRESUMEN
A Gram-positive, non-endospore-forming bacterium, designated strain SK 18(T), was isolated from surface soil of a landfill site by dilution plating on trypticase soy broth agar. Preliminary characterization of strain SK 18(T) via biochemical tests, analysis of fatty acid methyl esters and partial 16S rRNA gene sequencing placed it within the genus Microbacterium. Analysis of the cell wall indicated that the peptidoglycan was of cross-linkage type B, containing the amino acids lysine and ornithine and with muramic acid in the N-glycolyl form. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, an unidentified phospholipid and an unidentified glycolipid. The major fatty acids of the cell membrane were anteiso-C(17 : 0), anteiso-C(15 : 0) and iso-C(16 : 0). These data further strengthened placement of the strain within the genus Microbacterium. Strain SK 18(T) shared highest 16S rRNA gene sequence similarity (97.2 %) with Microbacterium ulmi DSM 16931(T). Levels of similarity with the type strains of all other recognized Microbacterium species were less than 97.0 %. DNA-DNA hybridization experiments with strain SK 18(T) and its closest relative, M. ulmi DSM 16931(T), revealed a low reassociation value of 39.0 % (σ = 3.8 %). Moreover, strain SK 18(T) showed a number of differences in phenotypic characteristics (colony colour, catalase activity, hydrolysis of polymers, acid production from sugars and oxidation of various substrates), and its DNA G+C content was also higher than that of M. ulmi DSM 16931(T). These data indicated that strain SK 18(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium immunditiarum sp. nov. is proposed. The type strain is SK 18(T) (= MTCC 7185(T) = JCM 14034(T)). An emended description of the genus Microbacterium is also provided.
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Actinomycetales/clasificación , Filogenia , Microbiología del Suelo , Actinomycetales/genética , Actinomycetales/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/análisis , Datos de Secuencia Molecular , Peptidoglicano/análisis , Fosfolípidos/análisis , ARN Ribosómico 16S/genética , Eliminación de Residuos , Análisis de Secuencia de ADN , Suelo/análisisRESUMEN
We study the dynamics of driven polymer translocation using both molecular dynamics (MD) simulations and a theoretical model based on the non-equilibrium tension propagation on the cis side subchain. We present theoretical and numerical evidence that the non-universal behavior observed in experiments and simulations are due to finite chain length effects that persist well beyond the relevant experimental and simulation regimes. In particular, we consider the influence of the pore-polymer interactions and show that they give a major contribution to the non-universal effects. In addition, we present comparisons between the theory and MD simulations for several quantities, showing extremely good agreement in the relevant parameter regimes. Finally, we discuss the potential limitations of the present theories.