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OBJECTIVES: To assess whether coexisting fetal growth restriction (FGR) influences pregnancy latency among women with preterm pre-eclampsia undergoing expectant management. Secondary outcomes assessed were indication for delivery, mode of delivery and rate of serious adverse maternal and perinatal outcomes. METHODS: We conducted a secondary analysis of the Pre-eclampsia Intervention (PIE) and the Pre-eclampsia Intervention 2 (PI2) trial data. These randomized controlled trials evaluated whether esomeprazole and metformin could prolong gestation of women diagnosed with pre-eclampsia between 26 and 32 weeks of gestation undergoing expectant management. Delivery indications were deteriorating maternal or fetal status, or reaching 34 weeks' gestation. FGR (defined by Delphi consensus) at the time of pre-eclampsia diagnosis was examined as a predictor of outcome. Only placebo data from PI2 were included, as the trial showed that metformin use was associated with prolonged gestation. All outcome data were collected prospectively from diagnosis of pre-eclampsia to 6 weeks after the expected due date. RESULTS: Of the 202 women included, 92 (45.5%) had FGR at the time of pre-eclampsia diagnosis. Median pregnancy latency was 6.8 days in the FGR group and 15.3 days in the control group (difference 8.5 days; adjusted 0.49-fold change (95% CI, 0.33-0.74); P < 0.001). FGR pregnancies were less likely to reach 34 weeks' gestation (12.0% vs 30.9%; adjusted relative risk (aRR), 0.44 (95% CI, 0.23-0.83)) and more likely to be delivered for suspected fetal compromise (64.1% vs 36.4%; aRR, 1.84 (95% CI, 1.36-2.47)). More women with FGR underwent a prelabor emergency Cesarean section (66.3% vs 43.6%; aRR, 1.56 (95% CI, 1.20-2.03)) and were less likely to have a successful induction of labor (4.3% vs 14.5%; aRR, 0.32 (95% CI, 0.10-1.00)), compared to those without FGR. The rate of maternal complications did not differ significantly between the two groups. FGR was associated with a higher rate of infant death (14.1% vs 4.5%; aRR, 3.26 (95% CI, 1.08-9.81)) and need for intubation and mechanical ventilation (15.2% vs 5.5%; aRR, 2.97 (95% CI, 1.11-7.90)). CONCLUSION: FGR is commonly present in women with early preterm pre-eclampsia and outcome is poorer. FGR is associated with shorter pregnancy latency, more emergency Cesarean deliveries, fewer successful inductions and increased rates of neonatal morbidity and mortality. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Metformina , Preeclampsia , Recién Nacido , Lactante , Embarazo , Femenino , Humanos , Resultado del Embarazo , Cesárea/efectos adversos , Preeclampsia/diagnóstico , Retardo del Crecimiento Fetal/etiología , Espera Vigilante , Metformina/uso terapéuticoRESUMEN
OBJECTIVE: To examine the association of prenatal alcohol exposure (PAE) on cognitive abilities and behaviour profiles of 4-year-old children. DESIGN: Prospective cohort study. SETTING: Cape Town, South Africa. POPULATION: A cohort of 500 children. METHODS: Children from the Safe Passage Study, which prospectively collected PAE, were included. Cognition and behavioural profiles were assessed. Children with and without PAE were compared. Mean scores were compared, with P ≤ 0.05 considered significant. Results were adjusted for confounding factors. MAIN OUTCOME MEASURES: The Kaufman Assessment Battery for children measured intellectual and mental ability; the NEPSY-II instrument assessed neurocognitive performance. The caregiver completed the Preschool Child Behaviour checklist to rate the child's problem behaviours and competencies. RESULTS: Two hundred children had no PAE, 117 children had mild to moderate PAE (with no binge episodes), 113 children had heavy PAE (with one or two binge episodes), and 70 children had very heavy PAE (with three or more binge episodes). Women who binge drank had significantly higher rates of smoking, marijuana use, and methamphetamine use. Low to moderate PAE had no effect on cognitive ability and behaviour. Very heavy PAE was associated with problems performing simultaneous as well as sequential functions, lower scores in the language and sensorimotor domain, and more attention and pervasive developmental problems. CONCLUSIONS: Low to moderate PAE was not associated with cognitive processing or developmental problems. Women who had many binge drinking episodes during pregnancy were the most at risk for cognitive processing, neurocognitive, and behaviour problems in their children at 4 years of age. TWEETABLE ABSTRACT: Low to moderate prenatal alcohol use was not associated with cognitive or behavioural problems in 4-year-olds.
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Consumo de Bebidas Alcohólicas/efectos adversos , Desarrollo Infantil/fisiología , Trastornos del Neurodesarrollo/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Preescolar , Femenino , Estudios de Seguimiento , Encuestas Epidemiológicas , Humanos , Masculino , Trastornos del Neurodesarrollo/epidemiología , Pruebas Neuropsicológicas , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios Prospectivos , Sudáfrica/epidemiologíaRESUMEN
The new generations of compact high output power-to-weight ratio internal combustion engines generate broadband torsional oscillations, transmitted to lightly damped drivetrain systems. A novel approach to mitigate these untoward vibrations can be the use of nonlinear absorbers. These act as Nonlinear Energy Sinks (NESs). The NES is coupled to the primary (drivetrain) structure, inducing passive irreversible targeted energy transfer (TET) from the drivetrain system to the NES. During this process, the vibration energy is directed from the lower-frequency modes of the structure to the higher ones. Thereafter, vibrations can be either dissipated through structural damping or consumed by the NES. This paper uses a lumped parameter model of an automotive driveline to simulate the effect of TET and the assumed modal energy redistribution. Significant redistribution of vibratory energy is observed through TET. Furthermore, the integrated optimization process highlights the most effective configuration and parametric evaluation for use of NES.
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The aim of this study was to map the genetic expression of the vitamin D metabolizing enzymes CYP27A, CYP27B1, CYP2R1, and CYP24A1 in the first trimester in different human fetal tissues. In addition, the gene expression was correlated with fetal age, season, and presence of single nucleotide polymorphisms (SNPs) in the genes encoding CYP27A1 (rs4674344), CYP2R1 (rs2060793), and CYP24A1 (rs6013897). Fetal samples from livers (n=60), kidneys (n=43), lungs (n=37), and intestines (n=14) were analyzed by quantitative PCR. In addition, the expression of the enzymes was also analyzed in adult livers (n=20). The highest expression of CYP2R1 and CYP24A1 was found in fetal kidney and lung. CYP27A1 was expressed at the highest levels in the liver and kidney and CYP27B1 had the highest levels in the kidney. The expression of fetal hepatic CYP2R1 and CYP27A1 was increased during summertime. Carriers of the G-allele of the rs2060793 SNP in the CYP2R1 gene, a genotype previously associated with rickets, had lower levels of CYP2R1 mRNA.In conclusion, this study suggest that the kidneys rather than the liver, may be of importance for fetal vitamin D metabolism, even for the 25-hydroxylation, during the first trimester. The results also suggest that the lungs and intestines are important for vitamin D metabolism in the fetus. Finally, GG- carriers of the rs2060793 SNP had significantly lower CYP2R1 expression and might be at risk for 25-hydroxyvitamin D deficiency.
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Feto/enzimología , Perfilación de la Expresión Génica , Primer Trimestre del Embarazo/genética , Vitamina D/metabolismo , Adolescente , Adulto , Anciano , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Femenino , Regulación Enzimológica de la Expresión Génica , Frecuencia de los Genes/genética , Genotipo , Edad Gestacional , Humanos , Hidroxilación , Hígado/embriología , Hígado/enzimología , Masculino , Persona de Mediana Edad , Especificidad de Órganos/genética , Polimorfismo de Nucleótido Simple/genética , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Estaciones del Año , Adulto JovenRESUMEN
The low-energy dynamics of a two-dof system composed of a grounded linear oscillator coupled to a lightweight mass by means of a spring with both cubic nonlinear and negative linear components is investigated. The mechanisms leading to intense energy exchanges between the linear oscillator, excited by a low-energy impulse, and the nonlinear attachment are addressed. For lightly damped systems, it is shown that two main mechanisms arise: Aperiodic alternating in-well and cross-well oscillations of the nonlinear attachment, and secondary nonlinear beats occurring once the dynamics evolves solely in-well. The description of the former dissipative phenomenon is provided in a two-dimensional projection of the phase space, where transitions between in-well and cross-well oscillations are associated with sequences of crossings across a pseudo-separatrix. Whereas the second mechanism is described in terms of secondary limiting phase trajectories of the nonlinear attachment under certain resonance conditions. The analytical treatment of the two aformentioned low-energy transfer mechanisms relies on the reduction of the nonlinear dynamics and consequent analysis of the reduced dynamics by asymptotic techniques. Direct numerical simulations fully validate our analytical predictions.
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PURPOSE: To evaluate the value of chest X-ray in the follow-up of surgically treated T1-3N0M0 renal cell carcinoma. METHODS: We performed retrospective analysis of patients that underwent surgical treatment of a localized renal cell carcinoma (T1-3N0M0) between January 1993 and July 2010. Data on frequency and results of performed chest X-rays were collected from patients' records. RESULTS: In 17.5 years, 249 patients with a T1-3N0M0 renal cell carcinoma underwent a radical or partial nephrectomy. In 221 patients, 823 chest X-rays were performed during a median follow-up of 3.3 years (range 0.5-17 years). In 19 patients, a pulmonary recurrence occurred, of which 10 were not detected by the regular follow-up. Of the 9 patients that were diagnosed with a pulmonary recurrence with a chest X-ray during follow-up, 7 were asymptomatic at the time of diagnosis, and the chest X-ray has led to the detection; 0.85 % of the performed chest X-rays (7/823) have led to the detection of asymptomatic lung metastases. CONCLUSIONS: Due to the low yield of chest X-ray for detection of asymptomatic pulmonary recurrences, it has very low clinical value in the follow-up after nephrectomy for T1-3N0M0 renal cell carcinoma.
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Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/secundario , Neoplasias Renales/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Radiografía Torácica , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Renales/patología , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/diagnóstico por imagen , Estadificación de Neoplasias , Nefrectomía , Examen Físico , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
We show that nonlinear inertial coupling between a linear oscillator and an eccentric rotator can lead to very interesting interchanges between regular and chaotic dynamical behavior. Indeed, we show that this model demonstrates rather unusual behavior from the viewpoint of nonlinear dynamics. Specifically, at a discrete set of values of the total energy, the Hamiltonian system exhibits non-conventional nonlinear normal modes, whose shape is determined by phase locking of rotatory and oscillatory motions of the rotator at integer ratios of characteristic frequencies. Considering the weakly damped system, resonance capture of the dynamics into the vicinity of these modes brings about regular motion of the system. For energy levels far from these discrete values, the motion of the system is chaotic. Thus, the succession of resonance captures and escapes by a discrete set of the normal modes causes a sequence of transitions between regular and chaotic behavior, provided that the damping is sufficiently small. We begin from the Hamiltonian system and present a series of Poincaré sections manifesting the complex structure of the phase space of the considered system with inertial nonlinear coupling. Then an approximate analytical description is presented for the non-conventional nonlinear normal modes. We confirm the analytical results by numerical simulation and demonstrate the alternate transitions between regular and chaotic dynamics mentioned above. The origin of the chaotic behavior is also discussed.
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Algoritmos , Retroalimentación , Dinámicas no Lineales , Oscilometría/métodos , Simulación por ComputadorRESUMEN
The effects of Mg concentration and annealing temperature on the characteristics of nanocrystalline Mg(x)Zn(1 - x)O thin films (where x = 0-0.4) were studied using electron microscopy and photoluminescence. The films were prepared by a sol-gel method. The solid solubility limit of MgO in ZnO for the sol-gel-derived Mg(x)Zn(1 - x)O films in the present study was determined to be â¼ 20 at.%. Microstructural characterization of the films showed that the wurtzite crystallites decrease in size with increase in Mg concentration up to the solubility limit. Increasing Mg concentration beyond the solubility limit resulted in a decrease in crystallinity of the films. The bandgap energy was found to increase with Mg concentration whereas the linewidth first increased and then decreased when the Mg concentration was increased beyond the solubility limit. Photoluminescence properties have been correlated to the microstructure of the films. A growth mechanism for Mg(x)Zn(1 - x)O nanocrystalline films under the present processing conditions has also been proposed.
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An accurate prognostic method for preterm birth (PTB) could avoid unnecessary treatment(s) with potentially negative effects. The objective was to explore the prognostic accuracy of commercially available bedside cervicovaginal biomarker tests in combination with cervical length (CL) compared to CL measurement alone and/or a biomarker test alone, for PTB within 7 days after testing symptomatic women at 22-34 weeks. The MEDLINE, Cochrane, Embase and Web of Science databases were searched from inception to August 28th, 2019. Seven hundred and eight articles were identified and screened using Rayyan. Studies reporting on the predictive accuracy of combined tests compared to CL or biomarker alone for the prediction of PTB within 7 days of testing in symptomatic women with intact membranes were included. A piloted data extraction form was used. Direct comparisons of the prognostic accuracy of the combination test with CL measurement or a biomarker alone were done, as well as comparisons of prognostic accuracy of the included combination tests (indirect comparisons). Twelve articles were included (seven on fetal fibronectin, four on phosphorylated insulin-like growth factor binding protein-1, one comparing both). A variety of CL cut-offs was reported. The results could not demonstrate superiority of a combination method compared to single methods. Due to data scarcity and quality, the superiority of either predictive test for PTB, either combination or single, cannot be demonstrated with this systematic review. We recommend further research to compare available biomarkers.
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Trabajo de Parto Prematuro , Nacimiento Prematuro , Biomarcadores , Medición de Longitud Cervical , Cuello del Útero/diagnóstico por imagen , Femenino , Fibronectinas , Humanos , Recién Nacido , Valor Predictivo de las Pruebas , Embarazo , Nacimiento Prematuro/diagnósticoRESUMEN
Attenuated Salmonella Enteriditis (ΔSE) recombinant vaccine vectors incorporating a Salmonella flagellar filament protein (fliC) subunit, a putative cell-mediated epitope, for expression of the lamB gene (encoding a maltose outer membrane porin), with or without co-expression of a putative immune-enhancing CD154 oligopeptide, were developed and compared with wild-type Salmonella Enteriditis (experiments 1 and 2) or the attenuated ΔSE empty vector (experiment 3) as initial vaccine candidates against Salmonella infection. A total of 3 experiments were performed to assess the infection and clearance rate of each of these constructs. Each construct or Salmonella Enteriditis was orally administered to broiler chicks at day of hatch by oral gavage (~10(8) cfu/chick). In experiments 1 to 3, liver-spleen and cecal tonsils were removed aseptically for recovery of wild-type Salmonella Enteriditis or ΔSE mutants. These experiments suggested that cell surface expression of fliC alone markedly increased the clearance rate of the vector at or before 21d postvaccination in all 3 experiments. In a fourth experiment, broilers were vaccinated with one of the vaccine constructs or the ΔSE empty vector and then challenged with wild-type Salmonella Typhimurium. At 19 d posthatch, 16 d postinfection, neither candidate protected against challenge significantly better than the ΔSE empty vector, although there was significantly less Salmonella recovered from vaccinated chickens as compared with nonvaccinated controls. These experiments indicate that these experimental vaccines did not protect against heterologous challenge or enhance clearance after Salmonella Typhimurium challenge; as such, their value as vaccines is limited. The increased clearance of the candidate vaccines, particularly the vector expressing fliC alone, may have value in that the fliC epitope may decrease the clearance time of other recombinant vectored Salmonella vaccines.
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Salmonelosis Animal/inmunología , Vacunas contra la Salmonella/genética , Animales , Enteritis/epidemiología , Enteritis/veterinaria , Vectores Genéticos , Hipersensibilidad Tardía/inmunología , Hipersensibilidad Tardía/veterinaria , Proteínas Recombinantes/inmunología , Salmonella/inmunología , Salmonella/aislamiento & purificación , Salmonelosis Animal/epidemiología , Salmonella typhimurium/inmunología , Salmonella typhimurium/aislamiento & purificación , Estados Unidos/epidemiologíaRESUMEN
UNLABELLED: With the announcement of the Government of Canada's Radon Guideline and increased public awareness of radon risk, more and more Canadians wish to test their homes for radon. Radon service providers available on the Internet have attracted many homeowners' attention. These services provide an easy and less expensive way for homeowners to test radon levels in their homes. However, a question has frequently been asked, 'How reliable are the radon testing services available on the Internet?' To answer this question, we ordered 36 radon testing kits from 10 service providers on the Internet. The test results showed that online radon testing services could collectively meet the performance requirement. However, the quality of a few service providers needs to be improved. PRACTICAL IMPLICATIONS: Indoor radon tests were performed with detectors ordered from 10 service providers available on the Internet. The results showed that online radon testing services could collectively meet the performance requirement. However, the quality of a few service providers needs to be improved.
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Comercio , Monitoreo del Ambiente/instrumentación , Internet , Radón/análisis , Canadá , Monitoreo del Ambiente/normas , Diseño de Equipo , Vivienda , Control de Calidad , Sensibilidad y EspecificidadRESUMEN
Radon has been identified as the second leading cause of lung cancer after tobacco smoking. Information on indoor radon concentrations is required to assess the lung cancer burden due to radon exposure. However, radon data in highly populated southern Ontario are very limited. Since radon in soil is believed to be the main source of radon in homes, measurements of soil gas radon concentrations can be used to estimate variations in radon potential of indoor environments. This study reports a transect survey of natural background variation in soil radon levels across southern Ontario. The results indicate that radon risk could be high in some areas of southern Ontario.
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Contaminantes Radiactivos del Aire/análisis , Contaminación del Aire Interior/análisis , Radón/análisis , Contaminantes Radiactivos del Suelo/análisis , Radiación de Fondo , Canadá , HumanosRESUMEN
The functional relationship of nucleosome positioning and gene expression is not known. Using high-copy plasmids, containing the yeast phosphate-repressible acid phosphatase gene (PHO5) and the TRP1/ARS1 vector system, I have determined the nucleosomal structure of the 5' region of the PHO5 gene and demonstrated that the nucleosomal positioning of this region is independent of orientation or position in the various plasmid constructions utilized. However, deletion of a 278-base pair BamHI-ClaI fragment from the 5'-flanking sequences of the PHO5 gene causes the nucleosome positioning to become dependent on orientation or position in the plasmids tested. Use of PHO5-CYC1-lACZ fusions have demonstrated that this DNA fragment contains the sequences responsible for the transcriptional regulation of the PHO5 gene in response to the level of phosphate in the growth media. The nucleosome positioning in the 5' region of PHO5 may be determined by an interaction with the sequences or machinery responsible for transcriptional regulation of the gene.
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ADN de Hongos/análisis , Nucleosomas/análisis , Proteínas Represoras/genética , Saccharomyces cerevisiae/genética , Factores de Transcripción/genética , Transcripción Genética , Fosfatasa Ácida/análisis , Secuencia de Bases , Enzimas de Restricción del ADN/metabolismo , Nucleasa Microcócica/metabolismo , Hibridación de Ácido Nucleico , Plásmidos , beta-Galactosidasa/análisisRESUMEN
The PHO80 and PHO85 gene products encode proteins necessary for the repression of transcription from the major acid phosphatase gene (PHO5) of Saccharomyces cerevisiae. The deduced amino acid sequences of these genes have revealed that PHO85 is likely to encode a protein kinase, whereas no potential function has been revealed for PHO80. We undertook several approaches to aid in the elucidation of the PHO80 function, including deletion analysis, chemical mutagenesis, and expression analysis. DNA deletion analysis revealed that residues from both the carboxy- and amino-terminal regions of the protein, amounting to a total of 21% of the PHO80 protein, were not required for function with respect to repressor activity. Also, 10 independent single-amino-acid changes within PHO80 which resulted in the failure to repress PHO5 transcription were isolated. Nine of the 10 missense mutations resided in two subregions of the PHO80 molecule. In addition, expression analysis of the PHO80 and PHO85 genes suggested that the PHO85 gene product was not necessary for PHO80 expression and that the PHO85 gene was expressed at much higher levels in the cell than was the PHO80 gene. Furthermore, high levels of PHO80 were shown to suppress the effect of a PHO85 deletion at a level close to full repression. Implications for the function of the negative regulators in this system are discussed.
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Fosfatasa Ácida/genética , Regulación Enzimológica de la Expresión Génica , Regulación Fúngica de la Expresión Génica , Genes Fúngicos , Genes Reguladores , Saccharomyces cerevisiae/genética , Transcripción Genética , Deleción Cromosómica , Genotipo , Cinética , Mutagénesis Sitio-Dirigida , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/crecimiento & desarrollo , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismoRESUMEN
We developed a high-copy-number plasmid system containing the entire structural and regulatory sequences of the phosphate-repressible acid phosphatase (PHO5) gene and the TRP1/ARS1 replicator sequences of the yeast Saccharomyces cerevisiae to investigate the mechanism of repression-derepression of transcription. The resulting plasmid was used to transform either wild-type cells or a number of strains which contain mutations in various trans-acting regulatory loci for the production of acid phosphatase. Results of analysis of mRNA levels isolated from the transformed strains grown under repressed or derepressed conditions suggested that normal transcriptional regulation of the gene persisted, although gene copy number was significantly increased. Analysis of changes in linking number (i.e., the number of negative supercoils) of the plasmid isolated under repressed and derepressed growth conditions revealed that the transcriptionally inactive plasmid contained approximately three more negative supercoils than the transcriptionally active plasmid. This difference in topological state was similarly seen in a plasmid containing a sequence-related acid phosphatase gene (PHO11) under the same regulatory control system, but it was not seen in plasmids isolated from some strains containing mutations which caused either fully constitutive or nonderepressible production of acid phosphatase. Finally, analysis of the nucleosome positioning along the inactive gene sequence revealed that an abnormally broad internucleosomal spacer is present in a region presumed to function in the regulation of transcription by the level of Pi in the growth media.
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Fosfatasa Ácida/genética , Genes Fúngicos , Genes Reguladores , Genes , Fosfatos/farmacología , Saccharomyces cerevisiae/genética , Transcripción Genética , Fosfatasa Ácida/biosíntesis , Represión Enzimática , Genes/efectos de los fármacos , Genes Fúngicos/efectos de los fármacos , Genotipo , Hibridación de Ácido Nucleico , Fenotipo , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/enzimologíaRESUMEN
The PHO85 gene of Saccharomyces cerevisiae encodes a cyclin-dependent kinase involved in both transcriptional regulation and cell cycle progression. Although a great deal is known concerning the structure, function, and regulation of the highly homologous Cdc28 protein kinase, little is known concerning these relationships in regard to Pho85. In this study, we constructed a series of Pho85-Cdc28 chimeras to map the region(s) of the Pho85 molecule that is critical for function of Pho85 in repression of acid phosphatase (PHO5) expression. Using a combination of site-directed and ethyl methanesulfonate-induced mutagenesis, we have identified numerous residues critical for either activation of the Pho85 kinase, interaction of Pho85 with the cyclin-like molecule Pho80, or substrate recognition. Finally, analysis of mutations analogous to those previously identified in either Cdc28 or cdc2 of Schizosaccharomyces pombe suggested that the inhibition of Pho85-Pho80 activity in mechanistically different from that seen in the other cyclin-dependent kinases.
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Quinasas Ciclina-Dependientes/genética , Quinasas Ciclina-Dependientes/metabolismo , Proteínas Represoras , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimología , Fosfatasa Ácida/biosíntesis , Secuencia de Aminoácidos , Proteína Quinasa CDC28 de Saccharomyces cerevisiae/genética , Proteína Quinasa CDC28 de Saccharomyces cerevisiae/metabolismo , Secuencia Conservada , Quinasas Ciclina-Dependientes/química , Ciclinas/metabolismo , Represión Enzimática , Proteínas Fúngicas/metabolismo , Prueba de Complementación Genética , Datos de Secuencia Molecular , Mutagénesis , Proteínas Recombinantes de Fusión/biosíntesis , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Alineación de Secuencia , Relación Estructura-ActividadRESUMEN
BACKGROUND: The aim of this study was to assess the feasibility and reproducibility of semi-automatic volumetric measurement of retroperitoneal lymph node metastases in testicular cancer (TC) patients treated with chemotherapy versus the standardized manual measurements based on RECIST criteria. METHODS: 21 TC patients with retroperitoneal lymph node metastases of testicular cancer were studied with a CT scan of chest and abdomen before and after cisplatin based chemotherapy. Three readers, a surgical resident, a radiological technician and a radiologist, assessed tumor response independently using computerized volumetric analysis with Vitrea software® and manual measurement according to RECIST criteria (version 1.1). Intra- and inter-rater variability were evaluated with intra class correlations and Bland-Altman analysis. RESULTS: Assessment of intra observer and inter observer variance proved non-significant in both measurement modalities. In particularly all intraclass correlation (ICC) values for the volumetric analysis were > .99 per observer and between observers. There was minimal bias in agreement for manual as well as volumetric analysis. CONCLUSION: In this study volumetric measurement using Vitrea software® appears to be a reliable, reproducible method to measure initial tumor volume of retroperitoneal lymph node metastases of testicular cancer after chemotherapy. Both measurement methods can be performed by experienced non-radiologists as well.
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Tomografía Computarizada de Haz Cónico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/secundario , Programas Informáticos , Neoplasias Testiculares/diagnóstico por imagen , Adulto , Anciano , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Variaciones Dependientes del ObservadorRESUMEN
INTRODUCTION: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 (MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1-like conditions. RESULTS: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. DISCUSSION: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. CONCLUSIONS: We therefore suggest that routine germline MEN1 mutation testing of all cases of "classical" MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 (Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients <30 years old with sporadic hyperparathyroidism and multigland hyperplasia.
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Análisis Mutacional de ADN/métodos , Neoplasia Endocrina Múltiple Tipo 1/genética , Proteínas Proto-Oncogénicas/genética , Australia , ADN/genética , ADN/aislamiento & purificación , Mutación de Línea Germinal , Humanos , Hiperparatiroidismo/genética , Datos de Secuencia Molecular , Neoplasia Endocrina Múltiple Tipo 1/clasificación , MutaciónRESUMEN
We describe and explore accelerating oscillatory fronts in sonic vacua with nonlocal interactions. As an example, a chain of particles oscillating in the plane and coupled by linear springs, with fixed ends, is considered. When one end of this system is harmonically excited in the transverse direction, one observes accelerated propagation of the excitation front, accompanied by an almost monochromatic oscillatory tail. Position of the front obeys the scaling law l(t) â¼ t(4/3). The frequency of the oscillatory tail remains constant, and the wavelength scales as λ â¼ t(1/3). These scaling laws result from the nonlocal effects; we derive them analytically (including the scaling coefficients) from a continuum approximation. Moreover, a certain threshold excitation amplitude is required in order to initiate the front propagation. The initiation threshold is evaluated on the basis of a simplified discrete model, further reduced to a completely integrable nonlinear system. Given their simplicity, nonlinear sonic vacua of the type considered herein should be common in periodic lattices.
RESUMEN
We study the dynamics and acoustics of a nonlinear lattice with fixed boundary conditions composed of a finite number of particles coupled by linear springs, undergoing in-plane oscillations. The source of the strongly nonlinearity of this lattice is geometric effects generated by the in-plane stretching of the coupling linear springs. It has been shown that in the limit of low energy the lattice gives rise to a strongly nonlinear acoustic vacuum, which is a medium with zero speed of sound as defined in classical acoustics. The acoustic vacuum possesses strongly nonlocal coupling effects and an orthogonal set of nonlinear standing waves [or nonlinear normal modes (NNMs)] with mode shapes identical to those of the corresponding linear lattice; in contrast to the linear case, however, all NNMs except the one with the highest wavelength are unstable. In addition, the lattice supports two types of waves, namely, nearly linear sound waves (termed "L waves") corresponding to predominantly axial oscillations of the particles and strongly nonlinear localized propagating pulses (termed "NL pulses") corresponding to predominantly transverse oscillating wave packets of the particles with localized envelopes. We show the existence of nonlinear nonreciprocity phenomena in the dynamics and acoustics of the lattice. Two opposite cases are examined in the limit of low energy. The first gives rise to nonreciprocal dynamics and corresponds to collective, spatially extended transverse loading of the lattice leading to the excitation of individual, predominantly transverse NNMs, whereas the second case gives rise to nonreciprocal acoutics by considering the response of the lattice to spatially localized, transverse impulse or displacement excitations. We demonstrate intense and recurring energy exchanges between a directly excited NNM and other NNMs with higher wave numbers, so that nonreciprocal energy exchanges from small-to-large wave numbers are established. Moreover, we show the existence of nonreciprocal wave interaction phenomena in the form of irreversible targeted energy transfers from L waves to NL pulses during collisions of these two types of waves. Additional nonreciprocal acoustics are found in the form of complex "cascading processes, as well as nonreciprocal interactions between L waves and stationary discrete breathers. The computational studies confirm the theoretically predicted transition of the lattice dynamics to a low-energy state of nonlinear acoustic vacum with strong nonlocality.