RESUMEN
Liquid crystalline elastomers (LCEs) are shape-changing materials that exhibit large deformations in response to applied stimuli. Local control of the orientation of LCEs spatially directs the deformation of these materials to realize a spontaneous shape change in response to stimuli. Prior approaches to shape programming in LCEs utilize patterning techniques that involve the detailed inscription of spatially varying nematic fields to produce sheets. These patterned sheets deform into elaborate geometries with complex Gaussian curvatures. Here, we present an alternative approach to realize shape-morphing in LCEs where spatial patterning of the crosslink density locally regulates the material deformation magnitude on either side of a prescribed interface curve. We also present a simple mathematical model describing the behavior of these materials. Further experiments coupled with the mathematical model demonstrate the control of the sign of Gaussian curvature, which is used in combination with heat transfer effects to design LCEs that self-clean as a result of temperature-dependent actuation properties.
RESUMEN
Skyrmions can be stabilized in magnetic systems with broken inversion symmetry and chiral interactions, such as Dzyaloshinskii-Moriya interactions (DMI). Further, compensation of magnetic moments in ferrimagnetic materials can significantly reduce magnetic dipolar interactions, which tend to favor large skyrmions. Tuning DMI is essential to control skyrmion properties, with symmetry breaking at interfaces offering the greatest flexibility. However, in contrast to the ferromagnet case, few studies have investigated interfacial DMI in ferrimagnets. Here we present a systematic study of DMI in ferrimagnetic CoGd films by Brillouin light scattering. We demonstrate the ability to control DMI by the CoGd cap layer composition, the stack symmetry and the ferrimagnetic layer thickness. The DMI thickness dependence confirms its interfacial nature. In addition, magnetic force microscopy reveals the ability to tune DMI in a range that stabilizes sub-100 nm skyrmions at room temperature in zero field. Our work opens new paths for controlling interfacial DMI in ferrimagnets to nucleate and manipulate skyrmions.
RESUMEN
BACKGROUND: Capecitabine and cyclophosphamide are active in patients with advanced breast cancer, have non-overlapping toxic effects and synergy pre-clinically. We explored the efficacy and toxic effect of an all-oral combination of capecitabine with cyclophosphamide versus capecitabine alone in a multicentre, randomized, phase II study. PATIENTS AND METHODS: Patients with locally advanced or metastatic breast cancer were randomized to treatment with capecitabine given continuously (666 mg/m(2) b.i.d. days 1-28) alone (C) or with oral cyclophosphamide (100 mg/m(2) days 1-14 of a 28-day cycle) (CCy) for up to six cycles. RESULTS: Eighty-two patients were randomized. There was no complete response. The proportions with partial response were 36% on C and 44% on CCy, a difference of 7.9% [95% confidence interval (CI) -13.4 to 29.1]. Significant toxic effect was uncommon: grade ≥3 diarrhoea in 4 (10%) versus 1 (3%) patients; grade ≥3 fatigue in 2 (5%) versus 5 patients (13%) and grade ≥2 hand-foot syndrome in 7 (17%) versus 11 (28%) patients receiving C versus CCy, respectively. Median progression-free survival was 3.1 months on C and 6.9 months on CCy, not significantly different statistically. There was no difference in overall survival. CONCLUSION: The difference in tumour response suggests a reasonable chance that CCy is superior to C alone.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Administración Oral , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Capecitabina , Ciclofosfamida/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Neoplasias Hepáticas/secundario , Metástasis Linfática , Persona de Mediana Edad , Neutropenia/inducido químicamente , Resultado del TratamientoRESUMEN
This research considered the impact on parents of children with bleeding disorders of the increased use of home-based treatment and greater parental responsibility for management of the condition. Although they have undoubted advantages, these changes also present parents with new challenges. Some found administration of the treatment difficult, and decisions about treatment and the everyday management of the condition can also prove problematic. Services should be aware of these issues and help parents access appropriate support.
Asunto(s)
Trastornos de la Coagulación Sanguínea/terapia , Cuidadores , Servicios de Atención de Salud a Domicilio , Calidad de Vida , Cuidadores/psicología , Niño , Manejo de la Enfermedad , Familia , Humanos , Relaciones Padres-Hijo , Padres , Grupos de AutoayudaRESUMEN
BACKGROUND: There is considerable interest in the role of different candidate loci in the development of asthma. This study investigates the association between asthma severity and previously identified polymorphisms at two sites within the beta2-adrenergic receptor (beta2AR) gene: the Arg16-->Gly16 and Gln27-->Glu27 alleles. METHODS: Restriction enzyme analysis of amplified beta2AR gene products (PCR-RFLP) was used to analyse the frequency of the Arg16-->Gly16 and Gln27-->Glu27 polymorphisms within the beta2AR gene in 95 severe asthmatic patients (with a markedly increased risk of death from asthma), 59 mild asthmatic patients, and a control group of 92 nonasthmatic subjects. RESULTS: The Gly16 polymorphism was significantly associated with asthma severity with odds ratios (95% CI) for the Gly16 allele being 1.56 (1.02-2.40, P = 0.04) and 0. 98 (0.61-1.57, P = 0.92) for the severe and mild asthma groups, respectively. The corresponding odds ratios (95% CI) for Gly16 homozygotes were 1.91 (0.82-4.41, P = 0.13) and 0.82 (0.35-1.92, P = 0.65) for the severe and mild asthma groups, respectively. There was no significant association between either polymorphism at amino acid 27 and asthma or asthma severity. CONCLUSIONS: We conclude that the polymorphisms of amino acids 16 and 27 of the beta2AR gene are not associated with the development of asthma per se, but that the Gly16 polymorphism may play a role in the pathogenesis of asthma severity.
Asunto(s)
Asma/genética , Receptores Adrenérgicos beta 2/genética , Adulto , Sustitución de Aminoácidos/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Heterocigoto , Humanos , Masculino , Mutación Puntual/genética , Reacción en Cadena de la Polimerasa , Polimorfismo Genético/genética , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
Inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate are Ca(2+)-regulating second messenger molecules which are generated via the cleavage of inositol lipids. We have previously shown that these species are autonomously generated in HL60 myeloid leukemia cells and that they may play a role in signalling the continuous proliferation of this cell line. Here we show that the activity of the 5-phosphomonoesterase (5-PME) enzyme which cleaves and inactivates these second messengers was strikingly reduced in HL60 cells compared to normal granulocytes or macrophages. Induction of differentiation of HL60 cells along the monocyte/macrophage or granulocytic pathways did not result in a significant increase in 5-PME activity. The activity of this enzyme was also low in extracts of bone marrow mononuclear cells from four patients with myeloid leukemia. A lesion in the 5-PME pathway may therefore result in the conservation of Ca(2+)-regulating second messengers in the HL60 cell line and in some myeloid leukemia cells. It is plausible that this lesion may co-operate with the autonomous cleavage of inositol lipids in the signalling of leukemic cell proliferation.
Asunto(s)
Inositol 1,4,5-Trifosfato/metabolismo , Leucemia Mieloide/metabolismo , Médula Ósea/metabolismo , Calcio/metabolismo , División Celular/fisiología , Fraccionamiento Celular , Humanos , Leucemia Mieloide/patología , Sistemas de Mensajero Secundario , Tritio , Células Tumorales CultivadasRESUMEN
Lymphocytes infected in vivo with HIV or lymphoblastoid cells exposed in vitro to either HIV or its envelope glycoprotein (gp120) show a defect in inositol polyphosphate-mediated signal transduction together with an associated abnormality in intracellular calcium regulation. The defect in patients reverses after treatment with the anti-retroviral agent zidovudine (AZT). We present evidence that the defect is at the level of the Ins (1,3,4,5)P4 5-phosphomonoesterase (PME) in these cells and that, though elevation of the intracellular ATP level partially down-regulates the activity of this enzyme, such changes alone are unable to account for the complete inhibition seen in HIV-infected cells.