RESUMEN
BACKGROUND: A submucous cleft palate and a congenitally short velum are diagnosed rather late, because symptoms are often mild. OBJECTIVES: The pre- and postoperative clinical symptoms for both conditions are presented. MATERIALS AND METHODS: The data of 180 patients with a submucous cleft palate (161) or congenitally short velum (19) were retrospective analyzed. In 23.3%, a syndromic association was found. RESULTS: Clinical findings for both conditions included middle ear problems, hypernasal speech, nasal penetration, the absence of the posterior nasal spine of the hard palate and/or a bifid uvula with a zona pellucida. The average age at diagnosis was 4.2 years in submucous clefts and 5.7 years in children with a congenitally short velum. Surgical palatoplasty with fusion of soft palate muscles and/or elongation of the soft palate was performed in 83.9% of the children, aiming to achieve sufficient velopharyngeal closure (VPC) with a significant decrease of symptoms and, hence, better conditions for speech therapy interventions. The overall success rate of the VPC was 63.7% with improvement in up to 2 of the 3 clinical symptoms (hypernasal speech, nasal penetration, middle ear problems). Hypernasal speech was more common (in 89.5%) in children with a congenitally short velum before surgery and in 81.3% 8 weeks after surgery; however, prior to surgery they had a short soft palate. CONCLUSION: Surgical intervention was particularly effective in children younger than 5 years. Syndromic diseases are disproportionately associated with soft palate defects.
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Fisura del Paladar , Insuficiencia Velofaríngea , Niño , Preescolar , Fisura del Paladar/complicaciones , Fisura del Paladar/cirugía , Humanos , Paladar Duro , Paladar Blando , Estudios Retrospectivos , Resultado del Tratamiento , Insuficiencia Velofaríngea/cirugíaRESUMEN
OBJECTIVES: The study examined the prevalence of stress, burnout, and coping, and the relationship between these variables among emergency physicians at a teaching hospital in Kingston, Jamaica. METHODS: Thirty out of 41 physicians in the Emergency Department completed the Maslach Burnout Inventory, Perceived Stress Scale, Ways of Coping Questionnaire, and a background questionnaire. Descriptive statistical analyses were conducted. RESULTS: Fifty per cent of study participants scored highly on emotional exhaustion; the scores of 53.3% also indicated that they were highly stressed. Stress correlated significantly with the emotional exhaustion and depersonalization components of burnout. Depersonalization was significantly correlated with two coping strategies: escape-avoidance and accepting responsibility; emotional exhaustion was also significantly correlated with escape-avoidance. CONCLUSION: Emergency physicians at the hospital scored high on stress and components of burnout. Interventions aimed at reducing the occupational contributors to stress and improving levels of coping will reduce the risk of burnout and enhance psychological well-being among emergency physicians.
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The ability to design technological solutions that address sustainability is considered pivotal to the future of the planet and its people. As technology professionals engineers are expected to play an important role in sustaining society. The present article aims at exploring sustainability concepts of newly enrolled engineering students in Denmark. Their understandings of sustainability and the role they ascribe to sustainability in their future professional practice is investigated by means of a critical discourse analysis including metaphor analysis and semiotic analysis. The sustainability construal is considered to delimit possible ways of dealing with the concept in practice along the engineering education pathway and in professional problem solving. Five different metaphors used by the engineering students to illustrate sustainability are identified, and their different connotative and interpretive implications are discussed. It is found that sustainability represents a dilemma to the engineering students that situates them in a tension between their technology fascination and the blame they find that technological progress bears. Their sustainability descriptions are collected as part of a survey containing among other questions one open-ended, qualitative question on sustainability. The survey covers an entire year group of Danish engineering students in the first month of their degree study.
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Comprensión , Conservación de los Recursos Naturales , Ingeniería/ética , Metáfora , Solución de Problemas/ética , Responsabilidad Social , Tecnología/ética , Recolección de Datos , Dinamarca , Ingeniería/educación , Humanos , Encuestas y CuestionariosAsunto(s)
Neoplasias de la Mama Masculina/diagnóstico , Melanoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Acantólisis/diagnóstico , Anciano , Biopsia , Neoplasias de la Mama Masculina/patología , Dermoscopía , Diagnóstico Diferencial , Humanos , Ictiosis/diagnóstico , Masculino , Melanoma/patología , Invasividad Neoplásica , Piel/patología , Neoplasias Cutáneas/patologíaRESUMEN
Orofacial clefts are one of the most common birth defects in humans with a prevalence of 1:700. Nonsyndromic cleft lip with or without cleft palate or isolated cleft palate show an incomplete separation of the oral cavity and the nasal space without any additional malformations. Beside complete cleft palate also submucous celft palates exist that are hidden below the intact mucosa. The aetiology of celfts is a complex interaction between environmental and genetic factors. Orofacial clefts cause many complications like feeding, speech and hearing problems needing a team of head and neck surgeons, oral and maxillofacial surgeons, phoniatricians and speech therapist for treatment. Often a genetic counselling is made for estimating the risk for the relatives.
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Labio Leporino/diagnóstico , Fisura del Paladar/diagnóstico , Labio Leporino/complicaciones , Labio Leporino/epidemiología , Labio Leporino/genética , Fisura del Paladar/complicaciones , Fisura del Paladar/epidemiología , Fisura del Paladar/genética , Terapia Combinada , Interacción Gen-Ambiente , Asesoramiento Genético , Humanos , Lactante , Recién Nacido , Grupo de Atención al Paciente , SíndromeRESUMEN
Organelles called centrosomes in metazoans or spindle pole bodies (SPBs) in yeast direct the assembly of a bipolar spindle that is essential for faithful segregation of chromosomes during mitosis. Abnormal accumulation of multiple centrosomes leads to genome instability, and has been observed in both tumour cells and cells with targeted mutations in tumour-suppressor genes. The defects that lead to centrosome amplification are not understood. We have recapitulated the multiple-centrosome phenotype in budding yeast by disrupting the activity of specific cyclin-dependent kinase (CDK) complexes. Our observations are reminiscent of mechanisms that govern DNA replication, and show that specific cyclin/CDK activities function both to promote SPB duplication and to prevent SPB reduplication.
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Transformación Celular Neoplásica/genética , Centrosoma/enzimología , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/metabolismo , Mitosis/fisiología , Proteínas de Saccharomyces cerevisiae , Huso Acromático/enzimología , Levaduras/genética , Ciclo Celular/genética , Ciclina B/genética , Ciclina B/metabolismo , Quinasas Ciclina-Dependientes/genética , Ciclinas/genética , Levaduras/metabolismoRESUMEN
BACKGROUND: Submucous cleft palate (SMCP) is often diagnosed very late and can cause velopharyngeal insufficiency with open nasal speech and Eustachian tube dysfunction. METHODS: A retrospective analysis of 106 patients (100 children, 6 adults) who had been surgically treated for SMCP was made. Age of diagnosis, physician who initially diagnosed the SMCP, typical symptoms for cleft palate, clinical examination of the palate, therapy options and accompanying diseases were evaluated. RESULTS: SMCP was diagnosed in 79 cases by a specialist for Phoniatrics/ENT surgery of the University and in 21 cases by a physician, who does not work at hospital at the age of 4.9 years. Main symptoms were Eustachian tube dysfunctions (61.3%) and hypernasal speech (48.1%). Typical findings of the palate were: reduced contraction (69.8%), lack of posterior nasal spine (55.7%) and bifid uvula (51.9%). In 18 patients a dysmorphic syndrome was observed and in 83% a conductive hearing loss which resolved after palatoplasty (often in combination with adenotomy and insertion of ventilation tubes). Following surgery 18 patients required speech therapy and of these 6 needed velopharyngoplasty due to continuing open nasal speech. CONCLUSIONS: SMCP is often diagnosed very late, though symptoms of velopharyngeal insufficiency such as open nasal speech, Eustachian tube dysfunction and reduced contraction of the palate with bifid uvula are present. It is also often found in children with craniofacial dysmorphic syndromes. We therefore recommend that all patients with such findings are examined by an appropriate specialist such as Phoniatrics, ENT-Surgeon and Oral-Maxillofacial Surgeon so that early diagnosis and palatoplasty can be performed.
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Fisura del Paladar/diagnóstico , Adenoidectomía , Adolescente , Adulto , Niño , Preescolar , Fisura del Paladar/cirugía , Terapia Combinada , Conducta Cooperativa , Anomalías Craneofaciales/diagnóstico , Anomalías Craneofaciales/cirugía , Femenino , Humanos , Comunicación Interdisciplinaria , Masculino , Grupo de Atención al Paciente , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Reoperación , Trastornos del Habla/etiología , Trastornos del Habla/cirugía , Insuficiencia Velofaríngea/etiología , Insuficiencia Velofaríngea/cirugía , Adulto JovenRESUMEN
The frequency of delayed function of kidney transplants varies greatly and is associated with quality of graft, donor age and the duration of cold ischemia time. Furthermore, body weight differences between donor and recipient can affect primary graft function, but the underlying mechanism is poorly understood. We transplanted kidney grafts from commensurate body weight (L-WD) or reduced body weight (H-WD) donor rats into syngeneic or allogeneic recipients. Twenty-four hours posttransplantation, serum creatinine levels in H-WD recipients were significantly higher compared to L-WD recipients indicating impaired primary graft function. This was accompanied by upregulation of IL-6 transcription and increased tubular destruction in grafts from H-WD recipients. Using DNA microarray analysis, we detected decreased expression of genes associated with kidney function and an upregulation of other genes such as Cyp3a13, FosL and Trib3. A single application of IL-6 into L-WD recipients is sufficient to impair primary graft function and cause tubular damage, whereas immediate neutralization of IL-6 receptor signaling in H-WD recipients rescued primary graft function with well-preserved kidney graft architecture and a normalized gene expression profile. These findings have strong clinical implication as anti-IL6R treatment of patients receiving grafts from lower-weight donors could be used to improve primary graft function.
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Peso Corporal/fisiología , Interleucina-6/fisiología , Trasplante de Riñón/fisiología , Transducción de Señal/fisiología , Animales , Apoptosis/fisiología , Creatinina/sangre , Hemo-Oxigenasa 1/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Trasplante de Riñón/patología , Túbulos Renales/patología , Masculino , Modelos Animales , Ratas , Ratas Endogámicas Lew , Ratas EndogámicasRESUMEN
The second biennial Salk Cell Cycle meeting convened on 22 June 2001 in San Diego, California. Organized by Tony Hunter and Susan Forsburg of the Salk Institute, the five-day conference was highlighted by enlightening science and plenty of San Diego sunshine. Presentations covered a broad range of contemporary cell-cycle topics, ranging from regulation of DNA replication and mitosis to DNA damage recognition and checkpoint control.
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Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiología , Animales , Cromatina/metabolismo , Replicación del ADN/fisiología , Genes cdc/fisiología , Humanos , Cinetocoros/química , MitosisRESUMEN
Elevated atmospheric CO2 treatments stimulated biomass production in Fe-sufficient and Fe-deficient barley plants, both in hydroponics and in soil culture. Root/shoot biomass ratio was increased in severely Fe-deficient plants grown in hydroponics but not under moderate Fe limitation in soil culture. Significantly increased biomass production in high CO2 treatments, even under severe Fe deficiency in hydroponic culture, indicates an improved internal Fe utilization. Iron deficiency-induced secretion of PS in 0.5 to 2.5 cm sub-apical root zones was increased by 74% in response to elevated CO2 treatments of barley plants in hydroponics but no PS were detectable in root exudates collected from soil-grown plants. This may be attributed to suppression of PS release by internal Fe concentrations above the critical level for Fe deficiency, determined at final harvest for soil-grown barley plants, even without additional Fe supply. However, extremely low concentrations of easily plant-available Fe in the investigated soil and low Fe seed reserves suggest a contribution of PS-mediated Fe mobilization from sparingly soluble Fe sources to Fe acquisition of the soil-grown barley plants during the preceding culture period. Higher Fe contents in shoots (+52%) of plants grown in soil culture without Fe supply under elevated atmospheric CO2 concentrations may indicate an increased efficiency for Fe acquisition. No significant influence on diversity and function of rhizosphere-bacterial communities was detectable in the outer rhizosphere soil (0-3 mm distance from the root surface) by DGGE of 16S rRNA gene fragments and analysis of marker enzyme activities for C-, N-, and P-cycles.
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Atmósfera , Dióxido de Carbono/análisis , Hordeum/metabolismo , Hierro/metabolismo , Clorofila/metabolismo , Electroforesis en Gel de Poliacrilamida , Hordeum/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética , Sideróforos/metabolismo , Microbiología del SueloRESUMEN
This study addresses the effect of transcription on replication, using a system based on autonomously replicating plasmids in human cells. We added transcriptional elements from the human cytomegalovirus promoter/enhancer and the human beta-actin promoter to autonomously replicating plasmids based on human sequences and found that the transcriptional elements inhibited plasmid replication. Furthermore, conditional inhibition of plasmid replication was demonstrated by using a tetracycline-responsive promoter. We found that replication activity of plasmids carrying this promoter was inversely correlated with promoter activity. Replication activity was partially restored on plasmids when a transcriptional termination sequence was placed directly downstream of the promoter element. Transcriptional activity of the promoters and the efficacy of the terminator sequence were confirmed by using steady-state RNA analysis. These experiments suggest that transcription inhibits DNA replication on these plasmids and that the degree of inhibition is dependent on transcription strength. The possible significance of these results for chromosomal DNA replication are discussed.
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Citomegalovirus/genética , Replicación del ADN , Genes Inmediatos-Precoces , Plásmidos/metabolismo , Transcripción Genética , Actinas/genética , Línea Celular , Cromosomas Humanos , ADN/biosíntesis , Replicación del ADN/efectos de los fármacos , ADN Viral/biosíntesis , Elementos de Facilitación Genéticos , Humanos , Riñón , Regiones Promotoras Genéticas/efectos de los fármacos , Mapeo Restrictivo , Regiones Terminadoras Genéticas , Tetraciclina/farmacologíaRESUMEN
We have isolated a heterogeneous collection of human genomic sequences which replicate autonomously when introduced into human cells. The novel strategy for the isolation of these sequences involved cloning random human DNA fragments into a defective Epstein-Barr virus vector. This vector alone was unable to replicate in human cells, but appeared to provide for the nuclear retention of linked DNA. The human sequences persist in a long-term replication assay (greater than 2 months) in the presence of the viral nuclear retention sequences. Using a short-term (4-day) assay, we showed that the human sequences are able to replicate in the absence of all viral sequences. The plasmids bearing human sequences were shown to replicate based on the persistence of MboI-sensitive plasmid DNA in the long-term assay and the appearance of DpnI-resistant DNA in the short-term assay. The human sequences were shown to be responsible for the replication activity and may represent authentic human origins of replication.
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Replicación del ADN , Genes , Secuencia de Bases , Núcleo Celular/metabolismo , Clonación Molecular , Marcadores Genéticos , Vectores Genéticos , Herpesvirus Humano 4/genética , Humanos , Plásmidos , ReplicónRESUMEN
orp2 is an essential gene of the fission yeast Schizosaccharomyces pombe with 22% identity to budding yeast ORC2. We isolated temperature-sensitive alleles of orp2 using a novel plasmid shuffle based on selection against thymidine kinase. Cells bearing the temperature-sensitive allele orp2-2 fail to complete DNA replication at a restrictive temperature and undergo cell cycle arrest. Cell cycle arrest depends on the checkpoint genes rad1 and rad3. Even when checkpoint functions are wild type, the orp2-2 mutation causes high rates of chromosome and plasmid loss. These phenotypes support the idea that Orp2 is a replication initiation factor. Selective spore germination allowed analysis of orp2 deletion mutants. These experiments showed that in the absence of orp2 function, cells proceed into mitosis despite a lack of DNA replication. This suggests either that the Orp2 protein is a part of the checkpoint machinery or more likely that DNA replication initiation is required to induce the replication checkpoint signal.
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Ciclo Celular/fisiología , Replicación del ADN/fisiología , Proteínas de Unión al ADN/fisiología , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces/genética , Secuencia de Bases , Cartilla de ADN , Proteínas de Unión al ADN/genética , Genes Esenciales , Mutagénesis , Complejo de Reconocimiento del Origen , Plásmidos , Schizosaccharomyces/citología , Timidina Quinasa/genéticaRESUMEN
We analyzed data of 76 consecutive patients with myelodysplastic syndrome (MDS) and isolated del(5q) (n=66) or del(5q) plus one additional chromosomal abnormality (n=10) included in our MDS database over the last 26 years. The median age of our patient population was 66.8 years. The male to female ratio was 1:1.7. In all, 14 patients (18%) had advanced MDS with an increased medullary blast count. A total of 17 patients (22%) had significant dysplasia in the nonmegakaryocytic cell lines. Nearly half of the study population showed erythroid hypoplasia in the bone marrow. The projected median survival of patients with isolated del(5q) is 146 months for a median follow-up of 67 months. Patients with an increased medullary blast count and those with an additional chromosomal abnormality have a significantly shorter overall survival (24 and 45 months, respectively) than patients with isolated del(5q). We did not find survival differences for different cytogenetic breakpoints, nor did the amount of dysplasia have an impact on survival in our population. In total, 29 patients have died. Deaths occurred primarily due to transformation into acute leukemia, infection, or cardiac failure. Our data support the current definition of a separate entity of MDS with del(5q) that has been suggested by the World Health Organization.
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Deleción Cromosómica , Cromosomas Humanos Par 5/genética , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Adulto , Anciano , Anciano de 80 o más Años , Células Precursoras Eritroides/patología , Femenino , Humanos , Cariotipificación , Leucocitos/patología , Masculino , Megacariocitos/patología , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
A comparison of auditory and visual perception of scatterplots showed similar correlation estimation performance in both modalities. The present study replicated this experiment using electrotactile (electrocutaneous) presentation of scatterplots on the fingertips and abdomen, as well as visual presentation. The correlation estimation task resulted in a slightly poorer performance on electrotactile scatterplots (abdomen r = +0.847; fingertip r = +0.723) compared with the previous Flowers auditory displays (r = +0.91). There were similar levels of performance in the visual (control) condition in both the studies (r for both approx. +0.91). The performance in the correlation estimation task was similar across the two electrotactile displays, with perhaps a slight, but not significant (p = 0.077), advantage for the abdominal array. However, a preliminary digit identification task on both displays produced a better performance on the fingertip display (p < 0.05), suggesting that the relative performance of the two displays may be task specific. The present results demonstrate electrotactile perception of complex graphs and provide useful information for improving future versions of tactile displays.
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Ceguera/rehabilitación , Auxiliares Sensoriales , Tacto , Interfaz Usuario-Computador , Abdomen , Adulto , Estimulación Eléctrica/instrumentación , Estimulación Eléctrica/métodos , Femenino , Dedos , Humanos , Masculino , PsicofísicaRESUMEN
PURPOSE OF INVESTIGATION: Regulatory elements of the 5'-flanking region of the DNA-repair gene Rad51 were analysed to characterise pathological alterations of Rad51 mRNA expression during tumour development. METHODS: Various fragments of the Rad51 promoter were cloned into the pGL3 reporter vector and the respective promoter activity was determined by luciferase assays in transfected U2-OS cells. Transcription factor binding was identified using Protein/DNA arrays. RESULTS: The region encompassing base pairs -204 to -58 was identified as crucial for Rad51 gene transcription. Down regulator sequences are present upstream (-305 to -204) and downstream (-48 and +204) of this core promoter element. Promoter activity is significantly enhanced by substituting G at the polymorphic positions +135 and +172 for C and T, respectively. Transcription factors Ets1/PEA3, E2F1, p53, EGR1, and Stat5 were identified as relevant for regulating expression of Rad51. CONCLUSION: We identified three separate cis-sequence elements within the Rad51 transcriptional promoter, one ensuring basal levels of expression and two elements limiting expression to relatively low levels. The characterisation of transcription factor binding might help to explain high-level expression of Rad51 in a variety of solid tumours. The polymorphic sites appear important for the increased risk of breast and/or ovarian cancer for BRCA2 mutation carriers.
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Regulación Neoplásica de la Expresión Génica , Neoplasias de los Genitales Femeninos/genética , Regiones Promotoras Genéticas , Recombinasa Rad51/genética , Transcripción Genética , Región de Flanqueo 5' , Secuencia de Bases , Reparación del ADN , Factores de Transcripción E2F , Femenino , Humanos , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Expressed sequence tag (EST) databases represent a large volume of information on expressed genes including tissue type, expression profile and exon structure. In this study we create an extensive data set of human alternative splicing. We report the analysis of 7867 non-redundant mRNAs, 3011 of which contained alternative splice forms (38% of all mRNAs analysed). From a total of 12572 ESTs 4560 different possible alternative splice forms were detected. Interestingly, 70% of the alternative splice forms correspond to exon deletion events with only 30% exonic insertions. We experimentally verified 19 different splice forms from 16 genes in a total subset of 20 studied; all of the respective genes are of medical relevance.
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Empalme Alternativo , Proteínas/genética , ARN Mensajero/química , Bases de Datos Factuales , Exones , Eliminación de Gen , Humanos , Programas InformáticosRESUMEN
A total of 47 primary squamous cell carcinomas of the tongue were analysed by DNA flow cytometry. With respect to their clonal DNA content two distinct tumor groups could be distinguished. In 14 cases the tumors (29.8%) were dipoid, whereas in 33 cases (70.2%) additional cell lines characterized by abnormal DNA content could be detected. A significant increase of aneuploid cases with tumor size as well as with decreasing histological differentiation could be detected. Aneuploid cell lines are lacking in T1 as well as in most G1 carcinomas but predominate in T3 and G3. Furthermore, cervical lymph node involvement was recognized in the majority of aneuploid primary carcinomas (81.8%) but was largely lacking in diploid tumors (21.4%). Hence, the presence of aneuploid cell lines is clearly connected with clinical and histopathological parameters, each of which have turned out to worsen the prognosis in tongue carcinomas.
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Carcinoma de Células Escamosas/análisis , ADN de Neoplasias/análisis , Ploidias , Neoplasias de la Lengua/análisis , Carcinoma de Células Escamosas/patología , Citometría de Flujo , Humanos , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Lengua/patologíaRESUMEN
Shuttle vectors based on Epstein-Barr virus (EBV) replicate autonomously in the nuclei of human cells. These vectors represent reasonable models for chromosomes, have low background mutation frequencies, and have been useful for studying induced mutation in human cells. Two improvements in the EBV vector system are discussed. Attempts are described to increase vector copy number per cell by using a limited period of replication driven by the simian virus 40 (SV40) origin of replication. Isolation of human sequences that can replace the viral origin of replication in providing for autonomous replication of the vectors is also described. These improvements are leading toward shuttle vectors that are more efficient and more closely resemble authentic chromosomes.
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Vectores Genéticos , Herpesvirus Humano 4/genética , Pruebas de Mutagenicidad/métodos , Células Cultivadas , Replicación del ADN , Humanos , Recombinación Genética , Selección Genética , Transfección , Replicación ViralRESUMEN
Two experiments were conducted to probe for performance differences between early-semester subjects and late-semester subjects in an introductory psychology subject pool. In Experiment 1A, hypotheses regarding changes in performance included differential effort, changes in subjects' attention to the task, and changes in subjects' sensitivity. A signal detection paradigm was used, and 278 subjects were sampled over the course of the semester. No evidence of changes in subject performance was found, in spite of sufficient power to detect relevant patterns of change. The results of a replication (N = 135) were consistent with those of Experiment 1A. Experiment 2 (N = 118) employed a text comprehension task to examine possible differences in subject performance with a more cognitive task. Again, there was no evidence to support the idea that late-semester subjects were performing differently from early-semester subjects.