RESUMEN
Using the fusion-evaporation reaction ^{96}Ru(^{58}Ni,p4n)^{149}Lu and the MARA vacuum-mode recoil separator, a new proton-emitting isotope ^{149}Lu has been identified. The measured decay Q value of 1920(20) keV is the highest measured for a ground-state proton decay, and it naturally leads to the shortest directly measured half-life of 450_{-100}^{+170} ns for a ground-state proton emitter. The decay rate is consistent with l_{p}=5 emission, suggesting a dominant πh_{11/2} component for the wave function of the proton-emitting state. Through nonadiabatic quasiparticle calculations it was concluded that ^{149}Lu is the most oblate deformed proton emitter observed to date.
RESUMEN
There is sparse direct experimental evidence that atomic nuclei can exhibit stable "pear" shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity in radium isotopes, electric octupole (E3) matrix elements have been determined for transitions in ^{222,228}Ra nuclei using the method of sub-barrier, multistep Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN. The observed pattern of E3 matrix elements for different nuclear transitions is explained by describing ^{222}Ra as pear shaped with stable octupole deformation, while ^{228}Ra behaves like an octupole vibrator.
RESUMEN
The first 2^{+} and 3^{-} states of the doubly magic nucleus ^{132}Sn are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The ^{132}Sn ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a ^{206}Pb target. Deexciting γ rays from the low-lying excited states of the target and the projectile are recorded in coincidence with scattered particles. The reduced transition strengths are determined for the transitions 0_{g.s.}^{+}â2_{1}^{+}, 0_{g.s.}^{+}â3_{1}^{-}, and 2_{1}^{+}â3_{1}^{-} in ^{132}Sn. The results on these states provide crucial information on cross-shell configurations which are determined within large-scale shell-model and Monte Carlo shell-model calculations as well as from random-phase approximation and relativistic random-phase approximation. The locally enhanced B(E2;0_{g.s.}^{+}â2_{1}^{+}) strength is consistent with the microscopic description of the structure of the respective states within all theoretical approaches. The presented results of experiment and theory can be considered to be the first direct verification of the sphericity and double magicity of ^{132}Sn.
Asunto(s)
Endoscopía/métodos , Sialadenitis/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Finlandia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The beam quality correction factor, [Formula: see text], which corrects for the difference in the ionization chamber response between the reference and clinical beam quality, is an integral part of radiation therapy dosimetry. The uncertainty of [Formula: see text] is one of the most significant sources of uncertainty in the dose determination. To improve the accuracy of available [Formula: see text] data, four partners calculated [Formula: see text] factors for 10 ionization chamber models in linear accelerator beams with accelerator voltages ranging from 6 MV to 25 MV, including flattening-filter-free (FFF) beams. The software used in the calculations were EGSnrc and PENELOPE, and the ICRU report 90 cross section data for water and graphite were included in the simulations. Volume averaging correction factors were calculated to correct for the dose averaging in the chamber cavities. A comparison calculation between partners showed a good agreement, as did comparison with literature. The [Formula: see text] values from TRS-398 were higher than our values for each chamber where data was available. The [Formula: see text] values for the FFF beams did not follow the same [Formula: see text], [Formula: see text] relation as beams with flattening filter (values for 10 MV FFF beams were below fits made to other data on average by 0.3%), although our FFF sources were only for Varian linacs.
Asunto(s)
Fotones/uso terapéutico , Radiometría/instrumentación , Algoritmos , Método de Montecarlo , Aceleradores de Partículas , Fantasmas de Imagen , Efectividad Biológica Relativa , Incertidumbre , AguaRESUMEN
The IAEA is currently coordinating a multi-year project to update the TRS-398 Code of Practice for the dosimetry of external beam radiotherapy based on standards of absorbed dose to water. One major aspect of the project is the determination of new beam quality correction factors, k Q , for megavoltage photon beams consistent with developments in radiotherapy dosimetry and technology since the publication of TRS-398 in 2000. Specifically, all values must be based on, or consistent with, the key data of ICRU Report 90. Data sets obtained from Monte Carlo (MC) calculations by advanced users and measurements at primary standards laboratories have been compiled for 23 cylindrical ionization chamber types, consisting of 725 MC-calculated and 179 experimental data points. These have been used to derive consensus k Q values as a function of the beam quality index TPR20,10 with a combined standard uncertainty of 0.6%. Mean values of MC-derived chamber-specific [Formula: see text] factors for cylindrical and plane-parallel chamber types in 60Co beams have also been obtained with an estimated uncertainty of 0.4%.
Asunto(s)
Radioisótopos de Cobalto/análisis , Método de Montecarlo , Fotones/uso terapéutico , Radiometría/métodos , Radiometría/normas , Consenso , Humanos , Planificación de la Radioterapia Asistida por Computador , Efectividad Biológica Relativa , IncertidumbreRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, which would indicate CP violation and hence probe physics beyond the Standard Model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we observed the low-lying quantum states in 224Rn and 226Rn by accelerating beams of these radioactive nuclei. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.
RESUMEN
Mitogen withdrawal triggers myogenic differentiation in skeletal myoblasts in culture. We have examined the expression of the proto-oncogene c-jun during this process in mouse C2C12 myoblasts. c-jun belongs to a family of immediate early genes whose expression is activated in cultured cells in response to the addition of serum growth factors. Interestingly, expression of c-jun was maintained in mouse C2C12 and rat L6 myoblasts undergoing myogenic differentiation under low-serum conditions. Previously it has been reported that expression of c-jun is downregulated during differentiation of C2 cells. However, our results using C2C12 cells, a subclone of the C2 line, show that c-jun mRNA, protein and the activator-protein 1 (AP-1) DNA-binding activity were easily detected in proliferating myoblasts and differentiated myotubes. Although overexpression of c-jun has been shown to block myogenic differentiation in C2 cells, results presented here suggest that expression of c-jun at physiological levels may not interfere with skeletal myogenesis.
Asunto(s)
Regulación de la Expresión Génica , Genes jun , Músculos/citología , Proteínas Proto-Oncogénicas c-jun/genética , Animales , Secuencia de Bases , Western Blotting , Diferenciación Celular , Línea Celular , Proteínas de Unión al ADN/metabolismo , Técnicas In Vitro , Ratones , Datos de Secuencia Molecular , Proteínas Musculares/genética , Oligodesoxirribonucleótidos/química , ARN Mensajero/genética , RatasRESUMEN
The 3-year efficacy of lovastatin alone or in combination with colestipol was evaluated in 54 patients with type 2 hyperlipoproteinemia (22 non-familial and 32 familial hypercholesterolemic patients). A sufficient and sustained reduction in LDL cholesterol was achieved in non-familial hypercholesterolemia with lovastatin alone (average dose 74 mg/day, range 40-80 mg/d), whereas combination therapy with lovastatin 80 mg/d and colestipol (average dose 11.9 g/d, range 5-20 g/d) was required in familial hypercholesterolemia. The percentage changes from baseline at 3 years in serum LDL cholesterol, HDL cholesterol and total triglycerides were in the lovastatin-only group -53%, +10% and -15%, respectively, and in the two-drug group -58%, +22% and -18%, respectively. A subgroup analysis in patients with non-familial hypercholesterolemia indicated that the lipid-modifying effects of lovastatin were similar in type 2A and 2B phenotypes, except for a greater triglyceride lowering effect in type 2B. The lovastatin-alone regimen was well tolerated, whereas addition of colestipol caused subjective side effects in many patients. Serious side effects or discontinuations due to therapies did not occur. Both therapies caused slight but significant increases (within normal limits) in average serum transaminase levels. After 36 months a significant rise of 1.7 kg in mean body weight was observed in the lovastatin-only group. The ophthalmological follow-up did not reveal any cataractogenic effect attributable to treatment during the 3.8-year follow-up period.
Asunto(s)
Colestipol/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Lovastatina/uso terapéutico , Poliaminas/uso terapéutico , Adulto , Anciano , LDL-Colesterol/sangre , Femenino , Estudios de Seguimiento , Humanos , Hipercolesterolemia/sangre , Hiperlipoproteinemia Tipo II/sangre , Lípidos/sangre , Lipoproteínas/sangre , Lovastatina/efectos adversos , Masculino , Persona de Mediana Edad , Probucol/uso terapéutico , Triglicéridos/sangreRESUMEN
Hypercholesterolemia clustering in families not explained by either low density lipoprotein (LDL)-receptor mutations producing familial hypercholesterolemia (FH), or the apolipoprotein B (apo B) Arg3500-->Gln mutation with familial defective apo B (FDB), is common in the Finnish population. In search of previously unknown apo B mutations, we screened exons 26 to 29 of the apo B gene in 68 Finnish severely hypercholesterolemic (> or = 8 mmol/l) non-FH, non-FDB patients, using a single-strand conformation polymorphism analysis based screening method. Four rare and two polymorphic previously unreported DNA variations were detected. The rare variants were a three-nucleotide deletion, with the deletion of Asp2186, an A11961-->G change leading to a Thr3918-->Ala change, a T12922-->G change causing a Val4238-->Ala substitution, and a neutral T12935-->C change leading to a new RsaI cutting site. The polymorphic G12937-->C and G13569-->A changes leading to Arg4243-->Thr and Ala4454-->Thr substitutions, respectively, had minor allele frequencies of 0.03 and 0.02. None of these variants seemed to explain the hyperlipidemia in these patients. A major Finnish mutation causing severe hypercholesterolemia is unlikely to exist in the 3' two-thirds of the coding area of the apo B gene.
Asunto(s)
Apolipoproteínas B/genética , Código Genético , Pruebas Genéticas , Variación Genética , Hipercolesterolemia/genética , Secuencia de Bases , Exones , Finlandia , Frecuencia de los Genes , Haplotipos , Humanos , Lípidos/sangre , Linaje , Polimorfismo Genético , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
Sequential stimulation during one muscle contraction of several compartments of a motor nerve, using multiple-electrodes, allows individual nerve-muscle compartments to be stimulated at fairly low frequencies. This provides time for recovery even during muscle contraction. However, the whole muscle is stimulated at near to its optimum fusion frequency, which provides smooth muscle contraction. This stimulation system imitates the natural activation of skeletal muscle. The new phrenic nerve stimulator described utilises the principle of sequential motor nerve stimulation. It also incorporates a sigh function. The sigh current recruits additional axons at certain intervals and thus creates and keeps available a reserve of conditioned muscle. Clinical advantages result: the conditioning phase after the beginning of long-term phrenic nerve stimulation for electroventilation is shortened and muscle fatigue is delayed. A need of increase of gas exchange can be answered by increasing tidal volume instead of respiration rate alone.
Asunto(s)
Terapia por Estimulación Eléctrica/instrumentación , Adulto , Anciano , Electrodos Implantados , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Contracción Muscular , Nervio Frénico/fisiología , Insuficiencia Respiratoria/terapiaRESUMEN
Electron radiotherapy is applied to treat the chest wall close to the mediastinum. The performance of the GGPB and eMC algorithms implemented in the Varian Eclipse treatment planning system (TPS) was studied in this region for 9 and 16 MeV beams, against Monte Carlo (MC) simulations, point dosimetry in a water phantom and dose distributions calculated in virtual phantoms. For the 16 MeV beam, the accuracy of these algorithms was also compared over the lung-mediastinum interface region of an anthropomorphic phantom, against MC calculations and thermoluminescence dosimetry (TLD). In the phantom with a lung-equivalent slab the results were generally congruent, the eMC results for the 9 MeV beam slightly overestimating the lung dose, and the GGPB results for the 16 MeV beam underestimating the lung dose. Over the lung-mediastinum interface, for 9 and 16 MeV beams, the GGPB code underestimated the lung dose and overestimated the dose in water close to the lung, compared to the congruent eMC and MC results. In the anthropomorphic phantom, results of TLD measurements and MC and eMC calculations agreed, while the GGPB code underestimated the lung dose. Good agreement between TLD measurements and MC calculations attests to the accuracy of "full" MC simulations as a reference for benchmarking TPS codes. Application of the GGPB code in chest wall radiotherapy may result in significant underestimation of the lung dose and overestimation of dose to the mediastinum, affecting plan optimization over volumes close to the lung-mediastinum interface, such as the lung or heart.
Asunto(s)
Algoritmos , Electrones/uso terapéutico , Pulmón/efectos de la radiación , Mediastino/efectos de la radiación , Método de Montecarlo , Fantasmas de Imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Radiometría , Dosificación RadioterapéuticaRESUMEN
We have established a novel transgenic rat line carrying human microtubule-associated protein Tau-40 with mutation P301L. hTau-40/P301L transgenic male and female rats were followed up to 2 years of age. The hTau-40/P301L rats expressed human tau mRNA and protein in the limbic cortex and associated white matter, hippocampus and spinal cord. With increasing age, the staining density for phosphorylated tau increased in all these areas. Neither silver stains nor Fluoro-Jade staining indicated the presence of dying neurons, or axonal degeneration, and there was no evidence of increased gliosis or inflammation. However, some neurons did display dendritic abnormalities, and immunoblots revealed the presence of sarcosyl insoluble tau. A large test battery revealed no behavioral abnormalities in these rats, except a mild hyperactivity in the elevated plus maze. In conclusion, this transgenic tau rat may be a useful model for 'pretangle' pathology, although in this study conditions were not sufficient to induce significant neuronal loss or behavioral deficits.
Asunto(s)
Química Encefálica/genética , Modelos Animales , Mutación/genética , Proteínas tau/química , Proteínas tau/genética , Animales , Femenino , Hipocampo/química , Hipocampo/metabolismo , Humanos , Sistema Límbico/química , Sistema Límbico/metabolismo , Masculino , Ratas , Ratas Transgénicas , Médula Espinal/química , Médula Espinal/metabolismoRESUMEN
Research on aging in model organisms has revealed different molecular mechanisms involved in the regulation of the lifespan. Studies on Saccharomyces cerevisiae have highlighted the role of the Sir2 family of genes, human Sirtuin homologs, as the longevity factors. In Caenorhabditis elegans, the daf-16 gene, a mammalian homolog of FoxO genes, was shown to function as a longevity gene. A wide array of studies has provided evidence for a role of the activation of innate immunity during aging process in mammals. This process has been called inflamm-aging. The master regulator of innate immunity is the NF-kappaB system. In this review, we focus on the several interactions of aging-associated signaling cascades regulated either by Sirtuins and FoxOs or NF-kappaB signaling pathways. We provide evidence that signaling via the longevity factors of FoxOs and SIRT1 can inhibit NF-kappaB signaling and simultaneously protect against inflamm-aging process.
Asunto(s)
Envejecimiento/metabolismo , Factores de Transcripción Forkhead/metabolismo , FN-kappa B/antagonistas & inhibidores , Transducción de Señal , Sirtuinas/metabolismo , Envejecimiento/inmunología , Envejecimiento/patología , Animales , Humanos , Longevidad , FN-kappa B/metabolismoRESUMEN
OBJECTIVE: Our aim was to study how different SERMs modulate the inflammatory responses induced by lipopolysaccharide (LPS) or unmethylated CpG-oligonucleotides in mouse and rat microglial cells. MATERIALS AND METHODS: Inflammatory responses of mouse N9 microglial cells and rat primary hippocampal microglia to lipopolysaccharide (LPS) exposure were recorded by the secretion of nitric oxide (NO) and cytokine IL-6 in two models where SERM was added either 24 h before LPS addition or simultaneously or even after the LPS exposure. The responses of 17beta-estradiol, tamoxifen, raloxifene and ICI 182.780 were compared. Responses were recorded by ELISA, Northern and EMSA assays. RESULTS: SERMs but not 17beta-estradiol induced a significant, concentration-dependent anti-inflammatory response both in rat primary microglial cells and in mouse N9 microglial cells. The response was observed both in NO and IL-6 secretion as well as in total IL-6 mRNA expression. We have recently observed that histone deacetylase (HDAC) inhibitors can potentiate the LPS-induced inflammatory response. Raloxifene and tamoxifen inhibited the potentiation of LPS response induced by trichostatin A, an HDAC inhibitor, in N9 microglia. A SERM-induced anti-inflammatory response was observed in acute models where SERM was added simultaneously or even up to 6 h later than LPS exposure. In contrast, the pretreatment of N9 microglia with tamoxifen or raloxifene for 30 h before LPS exposure did not provide any protection against the LPS response. We also observed that the raloxifene-induced protection in N9 microglia was connected to a decline of LPS-induced DNA binding activity of AP-1 but not that of NF-kappaB transcription factors. CONCLUSIONS: Our results show that tamoxifen, raloxifene and ICI 182.780 induce an anti-inflammatory response in acute models of mouse and rat microglial cells. It seems that this response is not estrogen receptor-mediated but, probably, is attributable to some SERM-induced modulation of LPS-activated pro-inflammatory signalling cascades.
Asunto(s)
Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Microglía/patología , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Animales , Astrocitos/citología , Northern Blotting , Proliferación Celular , Células Cultivadas , Islas de CpG , ADN/metabolismo , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Estradiol/análogos & derivados , Estradiol/metabolismo , Estradiol/farmacología , Fulvestrant , Hipocampo/citología , Inhibidores de Histona Desacetilasas , Histona Desacetilasas/metabolismo , Humanos , Interleucina-6/sangre , Interleucina-6/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Lipopolisacáridos/metabolismo , Ratones , Microglía/metabolismo , Óxido Nítrico/metabolismo , Oligonucleótidos/metabolismo , Unión Proteica , ARN Mensajero/metabolismo , Clorhidrato de Raloxifeno/farmacología , Ratas , Ratas Wistar , Tamoxifeno/farmacología , Factores de TiempoRESUMEN
Han-Wistar rats were exposed to a 194-200 h swimming protocol which caused a significant increase in the cardiac weight. The levels of various tissue antioxidants were assayed from the myocardium of the right ventricle and from the left ventricle (subendo- and subepimyocardium). This endurance training decreased the activities of catalase in the right ventricle and in the subendo- and subepimyocardium and Cu,Zn-superoxide dismutase in the subendomyocardium as well as the concentration of vitamin E in the right ventricle and in the subendomyocardium. Also, the activity of thioredoxin reductase decreased in each part of myocardium and that of glutathione reductase in the right ventricle and in the subepimyocardium. The activity of glucose-6-phosphate dehydrogenase increased in the right ventricle and in the subepimyocardium. The activity of glutathione peroxidase and the total tissue contents of carnosine and anserine and tissue sulphydryl groups remained unchanged as compared to the control group. The endurance training caused only minor changes in the regional distribution of antioxidants. The major findings were the disappearance of the difference in the activity of catalase between the right and the left ventricle and the increase in the activity of glucose-6-phosphate dehydrogenase as compared to that of the left ventricle. The results show that endurance training by swimming decreases the level of cardiac antioxidants. This decrease may be due to the increased oxygen metabolism and the subsequent increase in the formation of oxygen free radicals, which could deplete the antioxidant pool.
Asunto(s)
Antioxidantes/metabolismo , Miocardio/metabolismo , Resistencia Física , Animales , Dipéptidos/metabolismo , Masculino , Oxidorreductasas/metabolismo , Peroxidasas/metabolismo , Esfuerzo Físico , Ratas , Ratas Endogámicas , NataciónRESUMEN
The effect of blocking expression of a specific gene with antisense phosphodiester oligodeoxynucleotides on the coordinate regulation of myogenesis was studied. Different regions of both fast and slow troponin C (TnC) mRNAs were targeted for binding of the antisense oligomer. The 5'-cap region of both mRNAs was found to be the most effective target for inhibiting the expression of these genes. Approximately 40%-60% inhibition of expression of a specific isoform of TnC was achieved. However, inhibition of the TnC expression did not appreciably alter the pattern of myogenesis of mouse C2C12 cells. The differentiated murine muscle cells were able to cope with this reduced level of the target gene expression by antisense phosphodiester oligomers. We have also used a phosphorothioate oligomer targeted against a common sequence within the coding region of both fast and slow TnC mRNAs. This oligomer was found to be ineffective in blocking TnC gene expression.