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1.
Phys Rev Lett ; 132(18): 186502, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38759205

RESUMEN

Polarons-fermionic charge carriers bearing a strong companion lattice deformation-exhibit a natural tendency for self-localization due to the recursive interaction between electrons and the lattice. While polarons are ubiquitous in insulators, how they evolve in transitions to metallic and superconducting states in quantum materials remains an open question. Here, we use resonant inelastic x-ray scattering to track the electron-lattice coupling in the colossal magneto-resistive bi-layer manganite La_{1.2}Sr_{1.8}Mn_{2}O_{7} across its metal-to-insulator transition. The response in the insulating high-temperature state features harmonic emissions of a dispersionless oxygen phonon at small energy transfer. Upon cooling into the metallic state, we observe a drastic redistribution of spectral weight from the region of these harmonic emissions to a broad high energy continuum. In concert with theoretical calculations, we show that this evolution implies a shift in electron-lattice coupling from static to dynamic lattice distortions that leads to a distinct polaronic ground state in the low temperature metallic phase-a dynamic polaron liquid.

2.
Nature ; 563(7731): 374-378, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30429543

RESUMEN

High-temperature copper oxide superconductors consist of stacked CuO2 planes, with electronic band structures and magnetic excitations that are primarily two-dimensional1,2, but with superconducting coherence that is three-dimensional. This dichotomy highlights the importance of out-of-plane charge dynamics, which has been found to be incoherent in the normal state3,4 within the limited range of momenta accessible by optics. Here we use resonant inelastic X-ray scattering to explore the charge dynamics across all three dimensions of the Brillouin zone. Polarization analysis of recently discovered collective excitations (modes) in electron-doped copper oxides5-7 reveals their charge origin, that is, without mixing with magnetic components5-7. The excitations disperse along both the in-plane and out-of-plane directions, revealing its three-dimensional nature. The periodicity of the out-of-plane dispersion corresponds to the distance between neighbouring CuO2 planes rather than to the crystallographic c-axis lattice constant, suggesting that the interplane Coulomb interaction is responsible for the coherent out-of-plane charge dynamics. The observed properties are hallmarks of the long-sought 'acoustic plasmon', which is a branch of distinct charge collective modes predicted for layered systems8-12 and argued to play a substantial part in mediating high-temperature superconductivity10-12.

3.
Nat Mater ; 19(9): 1036, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32661388

RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

4.
Nat Mater ; 19(4): 381-385, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31959951

RESUMEN

The search continues for nickel oxide-based materials with electronic properties similar to cuprate high-temperature superconductors1-10. The recent discovery of superconductivity in the doped infinite-layer nickelate NdNiO2 (refs. 11,12) has strengthened these efforts. Here, we use X-ray spectroscopy and density functional theory to show that the electronic structure of LaNiO2 and NdNiO2, while similar to the cuprates, includes significant distinctions. Unlike cuprates, the rare-earth spacer layer in the infinite-layer nickelate supports a weakly interacting three-dimensional 5d metallic state, which hybridizes with a quasi-two-dimensional, strongly correlated state with [Formula: see text] symmetry in the NiO2 layers. Thus, the infinite-layer nickelate can be regarded as a sibling of the rare-earth intermetallics13-15, which are well known for heavy fermion behaviour, where the NiO2 correlated layers play an analogous role to the 4f states in rare-earth heavy fermion compounds. This Kondo- or Anderson-lattice-like 'oxide-intermetallic' replaces the Mott insulator as the reference state from which superconductivity emerges upon doping.

5.
Br J Dermatol ; 185(6): 1221-1231, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34105768

RESUMEN

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.


Asunto(s)
Alopecia , Ensayos Clínicos como Asunto , Guías como Asunto , Liquen Plano , Alopecia/tratamiento farmacológico , Cicatriz/tratamiento farmacológico , Cicatriz/etiología , Consenso , Humanos , Liquen Plano/patología , Cuero Cabelludo/patología
6.
J Synchrotron Radiat ; 27(Pt 4): 890-901, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33565997

RESUMEN

Experiments using a THz pump and an X-ray probe at an X-ray free-electron laser (XFEL) facility like the Linac Coherent Light Source II (LCLS II) require frequency-tunable (3 to 20 THz), narrow bandwidth (∼10%), carrier-envelope-phase-stable THz pulses that produce high fields (>1 MV cm-1) at the repetition rate of the X-rays and are well synchronized with them. In this paper, a two-bunch scheme to generate THz radiation at LCLS II is studied: the first bunch produces THz radiation in an electromagnet wiggler immediately following the LCLS II undulator that produces X-rays from the second bunch. The initial time delay between the two bunches is optimized to compensate for the path difference in THz transport. The two-bunch beam dynamics, the THz wiggler and radiation are described, as well as the transport system bringing the THz pulses from the wiggler to the experimental hall.

7.
Exp Cell Res ; 365(1): 85-96, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29476834

RESUMEN

Cell extensions are critical structures that enable matrix remodeling in wound healing and cancer invasion but the regulation of their formation is not well-defined. We searched for new proteins that mediated cell extension formation over collagen by tandem mass tagged mass spectrometry analysis of purified extensions in 3T3 fibroblasts. Unexpectedly, importin-5, ENH isoform 1b (PDLIM5) and 26 S protease regulatory subunit 6B (PSMC4) were more abundant (> 10-fold) in membrane-penetrating cell extensions than cell bodies, which was confirmed by immunostaining and immunoblotting and also observed in human gingival fibroblasts. After siRNA knockdown of these proteins and plating cells on grid-supported floating collagen gels for 6 h, formation of cell extensions and collagen remodeling were examined. Knockdown of importin-5 reduced collagen compaction (1.9-fold), pericellular collagen degradation (~ 1.8-fold) and number of cell extensions (~ 69%). Knockdown of PSMC4 reduced collagen compaction (~ 1.5-fold), pericellular collagen degradation (~ 1.7-fold) and number of cell extensions (~ 42%). Knockdown of PDLIM5 reduced collagen compaction (~ 1.6-fold) and number of cell extensions (~ 21%). Inhibition of the TGF-ß RI kinase, Smad3 or ROCK-II signaling pathways reduced the abundance of PDLIM5 in cell extensions but PSMC4 and importin-5 were reduced only by Smad3 or ROCK-II inhibitors. We conclude that these novel proteins are required for cell extension formation and their recruitment into extensions involves the Smad3 and ROCK signaling pathways.


Asunto(s)
Extensiones de la Superficie Celular/metabolismo , Fibroblastos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Línea Celular , Colágeno/metabolismo , Geles/metabolismo , Encía , Humanos , Ratones , Células 3T3 NIH , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Cicatrización de Heridas/fisiología
8.
Phytopathology ; 109(3): 418-427, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30256188

RESUMEN

Reports of spatial patterns of 'Candidatus Liberibacter asiaticus'-infected asymptomatic citrus trees and 'Ca. L. asiaticus'-positive Asian citrus psyllids (ACP) are rare, as are published relationships between huanglongbing (HLB), ACP, and weather. Here, spatial patterns of 'Ca. L. asiaticus'-positive asymptomatic and symptomatic trees were determined every half year in a small grove over 2.5 years, and of HLB-symptomatic trees and ('Ca. L. asiaticus'-positive) ACP populations every month in two commercial groves for 1 year. Spread of symptomatic trees followed that of asymptomatic 'Ca. L. asiaticus'-positive trees with <6 months' delay. 'Ca. L. asiaticus'-positive asymptomatic and symptomatic fronts moved at 2.5 to 3.6 m month-1. No spatial relationship was detected between ACP populations and HLB-infected trees. HLB incidence and 'Ca. L. asiaticus'-positive ACP dynamics were tentatively positively correlated with monthly rainfall data and, to a lesser extent, with average minimum temperature.


Asunto(s)
Citrus , Hemípteros , Rhizobiaceae , Animales , Citrus/metabolismo , Hemípteros/microbiología , Enfermedades de las Plantas , Rhizobiaceae/patogenicidad , Tiempo (Meteorología)
9.
Proc Natl Acad Sci U S A ; 113(51): 14645-14650, 2016 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-27930313

RESUMEN

The existence of charge-density-wave (CDW) correlations in cuprate superconductors has now been established. However, the nature of the CDW ground state has remained uncertain because disorder and the presence of superconductivity typically limit the CDW correlation lengths to only a dozen unit cells or less. Here we explore the field-induced 3D CDW correlations in extremely pure detwinned crystals of YBa2Cu3O2 (YBCO) ortho-II and ortho-VIII at magnetic fields in excess of the resistive upper critical field ([Formula: see text]) where superconductivity is heavily suppressed. We observe that the 3D CDW is unidirectional and possesses a long in-plane correlation length as well as significant correlations between neighboring CuO2 planes. It is significant that we observe only a single sharply defined transition at a critical field proportional to [Formula: see text], given that the field range used in this investigation overlaps with other high-field experiments including quantum oscillation measurements. The correlation volume is at least two to three orders of magnitude larger than that of the zero-field CDW. This is by far the largest CDW correlation volume observed in any cuprate crystal and so is presumably representative of the high-field ground state of an "ideal" disorder-free cuprate.

10.
Hum Reprod ; 33(6): 1071-1078, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29659826

RESUMEN

STUDY QUESTION: Are the concentrations of five criteria air pollutants associated with probabilities of biochemical pregnancy loss and intrauterine pregnancy in women? SUMMARY ANSWER: Increased concentrations of ambient particulate matter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian stimulation (COS) and after embryo transfer were associated with a decreased probability of intrauterine pregnancy. WHAT IS KNOWN ALREADY: Exposure to high ambient air pollution was suggested to be associated with low fertility and high early pregnancy loss in women. STUDY DESIGN, SIZE, DURATION: Using a retrospective cohort study design, we analysed 6621 cycles of 4581 patients who underwent one or more fresh IVF cycles at a fertility centre from January 2006 to December 2014, and lived in Seoul at the time of IVF treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: To estimate patients' individual exposure to air pollution, we computed averages of hourly concentrations of five air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3) measured at 40 regulatory monitoring sites in Seoul for each of the four exposure periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional hazards model were used to estimate probabilities of biochemical pregnancy loss and intrauterine pregnancy for an interquartile range (IQR) increase in each air pollutant concentration during each period, after adjusting for individual characteristics. We tested the robustness of the result using generalised linear mixed model, accounting for within-woman correlation. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate in multiple IVF cycles was 51.3% per person. Survival analysis showed that air pollution during periods 1 and 3 was generally associated with IVF outcomes. Increased NO2 (adjusted HR = 0.93, 95% CI: 0.87, 0.99) and CO (0.94, 95% CI: 0.89, 1.00) during period 1 were associated with decreased probability of intrauterine pregnancy. PM10 (0.92, 95% CI: 0.85, 0.99), NO2 (0.93, 95% CI = 0.86, 1.00) and CO (0.93, 95% CI: 0.87, 1.00) levels during period 3 were also inversely associated with intrauterine pregnancy. Both PM10 (1.17, 95% CI: 1.04 1.33) and NO2 (1.18, 95% CI: 1.03, 1.34) during period 3 showed positive associations with biochemical pregnancy loss. LIMITATIONS, REASONS FOR CAUTION: The district-specific ambient air pollution treated as an individual exposure may not represent the actual level of each woman's exposure to air pollution. Smoking, working status, parity or gravidity of women, and semen analysis data were not included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study provided evidence of an association between increased ambient concentrations of PM10, NO2 and CO and reduced probabilities for achieving intrauterine pregnancy using multiple IVF cycle data. Specifically, our results indicated that lower intrauterine pregnancy rates in IVF cycles may be linked to ambient air pollution during COS and the post-transfer period. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013 R1A6A3A04059017, 2016 R1D1A1B03933410 and 2018 R1A2B6004608) and the National Cancer Center of Korea (NCC-1810220-01). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Fertilización In Vitro/estadística & datos numéricos , Índice de Embarazo , Adulto , Contaminación del Aire/estadística & datos numéricos , Monóxido de Carbono/toxicidad , Femenino , Fertilización In Vitro/métodos , Humanos , Modelos Lineales , Dióxido de Nitrógeno/toxicidad , Material Particulado/toxicidad , Embarazo , Modelos de Riesgos Proporcionales , República de Corea , Estudios Retrospectivos
11.
Osteoporos Int ; 29(11): 2427-2435, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30039251

RESUMEN

The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment. INTRODUCTION: To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing. METHODS: We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing. RESULTS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1-17 years). The use of BPs was significantly associated with AFFs (p < 0.001, odds ratio = 25.65; 95% confidence interval = 10.74-61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment. CONCLUSIONS: The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.


Asunto(s)
Fracturas del Fémur/epidemiología , Curación de Fractura , Fracturas Espontáneas/epidemiología , Fracturas de Cadera/epidemiología , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Artritis Reumatoide/fisiopatología , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/farmacología , Estudios de Casos y Controles , Difosfonatos/efectos adversos , Difosfonatos/farmacología , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/etiología , Fracturas del Fémur/fisiopatología , Curación de Fractura/efectos de los fármacos , Fracturas Espontáneas/diagnóstico por imagen , Fracturas Espontáneas/etiología , Fracturas Espontáneas/fisiopatología , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/etiología , Fracturas de Cadera/fisiopatología , Humanos , Incidencia , Persona de Mediana Edad , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/fisiopatología , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/fisiopatología , Radiografía , República de Corea/epidemiología , Factores de Riesgo
12.
J Periodontal Res ; 53(5): 727-735, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29732558

RESUMEN

BACKGROUND AND OBJECTIVE: Growth factors are frequently incorporated into scaffolds to promote periodontal regeneration but many currently used scaffolds do not encourage cell migration towards the dentogingival junction. We examined the proliferation and migration of human gingival fibroblasts in a novel, physically robust, collagen-Vicryl™ membrane loaded with fibronectin (FN) and/or insulin-like growth factor (IGF-I). Biocompatibility of the membranes was evaluated in rat dorsal skin. MATERIAL AND METHODS: Chemotaxis was examined in Boyden chambers and cell migration by confocal imaging of membranes, which were fabricated from rat tail type I collagen with embedded Vicryl knitted mesh, IGF-I (50, 100 ng/mL) and FN (10 µg/mL). Membranes (Vicryl alone, collagen+Vicryl, collagen+Vicryl+IGF-I, collagen+Vicryl+FN') were implanted subcutaneously in 8 rats and were evaluated by histomorphometry after 7 and 14 days. RESULTS: IGF-I (50 or 100 ng/mL) promoted chemotaxis compared with vehicle controls (P = .02, P = .001, respectively). IGF-I did not affect cell proliferation. Incorporation of FN retarded time-dependent release of IGF-I from collagen gels. Three dimensional confocal microscopy imaging of cell migration through collagen+Vicryl membranes showed enhanced migration in the IGF+FN group compared to all other groups at 8, 10 and 14 days (P < .05). In a rat skin model, implanted membranes were surrounded by thin collagen capsules and mild inflammatory infiltrates. CONCLUSION: Incorporation of FN into IGF-I-loaded collagen+Vicryl membranes reduced IGF release from collagen and increased the migration of human gingival fibroblasts. The new membrane may promote healing and reformation of the dentogingival junction.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Colágeno/farmacología , Fibroblastos/efectos de los fármacos , Membranas Artificiales , Adulto , Animales , Materiales Biocompatibles/farmacología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Quimiotaxis/fisiología , Fibronectinas/farmacología , Humanos , Factor I del Crecimiento Similar a la Insulina/farmacología , Masculino , Microscopía Confocal , Permeabilidad , Poliglactina 910/farmacología , Ratas , Ratas Sprague-Dawley
13.
Phytopathology ; 108(12): 1420-1428, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29873608

RESUMEN

Citrus huanglongbing (HLB), associated with 'Candidatus Liberibacter asiaticus' (Las), disseminated by Asian citrus psyllid (ACP), has devastated citrus in Florida since 2005. Data on HLB occurrence were stored in databases (2005 to 2012). Cumulative HLB-positive citrus blocks were subjected to kernel density analysis and kriging. Relative disease incidence per county was calculated by dividing HLB numbers by relative tree numbers and maximum incidence. Spatiotemporal HLB distributions were correlated with weather. Relative HLB incidence correlated positively with rainfall. The focus expansion rate was 1626 m month-1, similar to that in Brazil. Relative HLB incidence in counties with primarily large groves increased at a lower rate (0.24 year-1) than in counties with smaller groves in hotspot areas (0.67 year-1), confirming reports that large-scale HLB management may slow epidemic progress.


Asunto(s)
Citrus/microbiología , Hemípteros/microbiología , Insectos Vectores/microbiología , Enfermedades de las Plantas/estadística & datos numéricos , Rhizobiaceae/fisiología , Animales , Florida , Enfermedades de las Plantas/microbiología , Análisis Espacio-Temporal , Árboles , Tiempo (Meteorología)
14.
J Eur Acad Dermatol Venereol ; 32(7): 1214-1221, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29633370

RESUMEN

BACKGROUND: Alopecia areata (AA) is a hair follicle-specific autoimmune disorder. Vitamin D deficiency has been associated with various autoimmune disorders for its immunomodulatory effects. However, in previous studies, there had been inconsistent association found between AA and vitamin D deficiency. OBJECTIVE: To demonstrate the differences of the mean serum 25-hydroxyvitamin D level and prevalence of vitamin D deficiency between AA patients and non-AA population. METHODS: A systematic review and meta-analysis of observational studies on AA and serum vitamin D levels and/or prevalence of vitamin D deficiency was performed searching MEDLINE, Cochrane, Web of Science and Google Scholar databases. RESULTS: In all, 14 studies including a total of 1255 AA subjects and 784 non-AA control were analysed. The mean serum 25-hydroxyvitamin D level was significantly lower in AA subjects (-8.52 ng/dL; 95% confidential interval; -5.50 to -11.53). The AA subjects had higher odds of vitamin D deficiency (odds ratio of 3.89; 2.02 to 7.49, mean prevalence of 73.8%; 59.1 to 84.6%). However, it was difficult to find clear correlation between serum 25-hydroxyvitamin D level and extent of hair loss in AA subjects. CONCLUSION: The AA subjects had lower serum 25-hydroxyvitamin D level, and vitamin D deficiency was highly prevalent compared to non-AA controls. Hence, vitamin D deficiency should be assessed in AA patients. Furthermore, nutritional supplementation of vitamin D or topical vitamin D analogues can be considered for AA patients with vitamin D deficiency. The limitation of this study is the highly heterogeneity of the included studies.


Asunto(s)
Alopecia Areata/sangre , Alopecia Areata/epidemiología , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Vitamina D/análogos & derivados , Humanos , Estudios Observacionales como Asunto , Prevalencia , Índice de Severidad de la Enfermedad , Vitamina D/sangre
15.
Biochim Biophys Acta ; 1853(10 Pt A): 2526-38, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26025676

RESUMEN

Migrating cells sense variations of stiffness in connective tissue matrices but how cells detect and respond to stiffness orientation is not defined. We examined cell extension formation on collagen with underlying support (vertical stiffness gradient) or on collagen laterally supported by nylon (lateral stiffness gradient). At 6 h after plating, cells plated on laterally-supported collagen exhibited >2-fold more abundant and ~2-fold longer cell extensions than cells plated on collagen with underlying support. We examined whether p21-activated kinase 1 (PAK1) influences extension formation that is dependent on the orientation of support. At 6 h after plating on collagen with underlying support, wild-type cell extensions were 40% shorter than PAK1 knockdown cells. In contrast, on laterally-supported collagen, wild-type cell extensions were 2-fold longer than PAK1 knockdown cells. In cells plated on laterally-supported collagen, there were ~2-fold reductions of collagen fiber alignment and compaction in PAK1 knockdown cells compared with wild-type cells. PAK1 knockdown did not affect collagen fiber alignment or compaction by cells plated on collagen with underlying support. Wild-type cells with lateral support of collagen exhibited 3-fold increases of phospho-myosin staining at 6h, which was 2-fold lower in PAK1 knockdown cells. In contrast, cells on collagen with underlying support showed no increase of phospho-myosin staining at any times. PAK1 knockdown did not affect α2 or ß1 integrin expression or function. We conclude that PAK1 is involved in the ability of cells to sense the orientation of stiffness in collagen substrates and generate contractile forces that affect cell extension formation.


Asunto(s)
Extensiones de la Superficie Celular/metabolismo , Colágeno/química , Integrina alfa2/metabolismo , Integrina beta1/metabolismo , Quinasas p21 Activadas/metabolismo , Animales , Extensiones de la Superficie Celular/genética , Técnicas de Silenciamiento del Gen , Integrina alfa2/genética , Integrina beta1/genética , Ratones , Miosinas/genética , Miosinas/metabolismo , Células 3T3 NIH , Quinasas p21 Activadas/genética
16.
Ann Oncol ; 27(4): 712-8, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26861608

RESUMEN

BACKGROUND: Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. PATIENTS AND METHODS: Participants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. RESULTS: The objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL-not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. CONCLUSION: The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Everolimus/administración & dosificación , Linfoma de Células T Periférico/tratamiento farmacológico , Fosfohidrolasa PTEN/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Esquema de Medicación , Everolimus/efectos adversos , Femenino , Humanos , Linfoma de Células T Periférico/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fosfohidrolasa PTEN/biosíntesis , Prednisona/administración & dosificación , Prednisona/efectos adversos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/genética , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversos
17.
Nat Mater ; 14(9): 883-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26147844

RESUMEN

Static strain in complex oxide heterostructures has been extensively used to engineer electronic and magnetic properties at equilibrium. In the same spirit, deformations of the crystal lattice with light may be used to achieve functional control across heterointerfaces dynamically. Here, by exciting large-amplitude infrared-active vibrations in a LaAlO3 substrate we induce magnetic order melting in a NdNiO3 film across a heterointerface. Femtosecond resonant soft X-ray diffraction is used to determine the spatiotemporal evolution of the magnetic disordering. We observe a magnetic melt front that propagates from the substrate interface into the film, at a speed that suggests electronically driven motion. Light control and ultrafast phase front propagation at heterointerfaces may lead to new opportunities in optomagnetism, for example by driving domain wall motion to transport information across suitably designed devices.

19.
Med J Malaysia ; 71(4): 186-192, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27770117

RESUMEN

INTRODUCTION: Open disclosure is poorly understood in Malaysia but is an ethical and professional responsibility. The objectives of this study were to determine: (1) the perception of parents regarding the severity of medical error in relation to medication use or diagnosis; (2) the preference of parents for information following the medical error and its relation to severity; and (3) the preference of parents with regards to disciplinary action, reporting, and legal action. METHODS: We translated and contextualised a questionnaire developed from a previous study. The questionnaire consisted of four case vignettes that described the following: medication error with a lifelong complication; diagnostic error with a lifelong complication; diagnostic error without lifelong effect; and medication error without lifelong effect. Each case vignette was followed by a series of questions examining the subject's perception on the above areas. We also determined the content validity of the questionnaire. We invited parents of Malaysian children admitted to the paediatric wards of Tuanku Jaafar Hospital to participate in the study. RESULTS: One hundred and twenty-three parents participated in the study. The majority of parents wanted to be told regarding the event. As the severity of the case vignettes increased, the desire for information, remedial action, acknowledgement of responsibility, compensation, punishment, legal action, and reporting to a higher agency also increased. The findings did not have strong evidence of a relationship with subject's demographics. CONCLUSION: This study gives insights into previously unexplored perspectives and preferences of parents in Malaysia regarding open disclosure. It also highlights the opportunity for more research in this area with potentially broad applications.


Asunto(s)
Errores Médicos , Padres , Revelación de la Verdad , Niño , Humanos , Malasia , Encuestas y Cuestionarios
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