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Linker histones play an essential role in chromatin packaging by facilitating compaction of the 11-nm fiber of nucleosomal "beads on a string." The result is a heterogeneous condensed state with local properties that range from dynamic, irregular, and liquid-like to stable and regular structures (the 30-nm fiber), which in turn impact chromatin-dependent activities at a fundamental level. The properties of the condensed state depend on the type of linker histone, particularly on the highly disordered C-terminal tail, which is the most variable region of the protein, both between species, and within the various subtypes and cell-type specific variants of a given organism. We have developed an in vitro model system comprising linker histone tail and linker DNA, which although very minimal, displays surprisingly complex behavior, and is sufficient to model the known states of linker histone-condensed chromatin: disordered "fuzzy" complexes ("open" chromatin), dense liquid-like assemblies (dynamic condensates), and higher-order structures (organized 30-nm fibers). A crucial advantage of such a simple model is that it allows the study of the various condensed states by NMR, circular dichroism, and scattering methods. Moreover, it allows capture of the thermodynamics underpinning the transitions between states through calorimetry. We have leveraged this to rationalize the distinct condensing properties of linker histone subtypes and variants across species that are encoded by the amino acid content of their C-terminal tails. Three properties emerge as key to defining the condensed state: charge density, lysine/arginine ratio, and proline-free regions, and we evaluate each separately using a strategic mutagenesis approach.
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DNA , Histonas , Nucleossomos , Histonas/química , Histonas/metabolismo , Histonas/genética , DNA/química , DNA/metabolismo , Nucleossomos/metabolismo , Nucleossomos/química , Cromatina/química , Cromatina/metabolismo , Cromatina/genética , Animais , HumanosRESUMO
BACKGROUND: Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and the clinical, serological and radiological associations of a cohort of Chinese patients. METHODS: A territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports. RESULTS: A total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001). CONCLUSIONS: 95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD.
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PURPOSE: To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. DESIGN: Cross-sectional, matched case-control comparison study. METHODS: This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. RESULTS: A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = -0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = -0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). CONCLUSIONS: IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.
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Síndromes do Olho Seco , Aparelho Lacrimal , Humanos , Masculino , Estudos Transversais , Síndromes do Olho Seco/diagnóstico , Glândulas Tarsais , Lágrimas/química , Imunoglobulina GRESUMO
Objective: This study aimed to examine the fidelity of intervention delivery and identify precursory factors contributing to the successful delivery and beneficial effects of family-oriented dignity therapy. Methods: This was a process evaluation with quantitative and qualitative methods alongside a randomized controlled trial from March to May 2019. Nonparametric statistics were used to analyze how participants' demographics (n â= â45 dyads) and process variables influenced the intervention effects. Fourteen patients, 11 family caregivers, and 11 nurses were interviewed to explore their perception of the intervention. Conventional content analysis was adopted to analyze the qualitative data. Results: The fidelity was achieved with minor deviations from the protocol. Higher educational level and higher income were significantly correlated with lower levels of existential distress (H â= â12.20, P â= â0.030) and higher spiritual well-being (H â= â-16.310, P â= â0.031), respectively. Higher levels of interest were significantly correlated with lower levels of existential distress (H â= â10.396, P â= â0.035) and peace of mind distress (H â= â-16.778, P â= â0.006) and higher levels of life meaning (H â= â-12.808, P â= â0.047). Patients who had higher response levels to the question were significantly correlated with lower levels of symptom distress (H â= â-13.879, P â= â0.035). Four major categories were identified from the interview data: (1) benefits of the intervention, (2) risks of the intervention, (3) factors that enhance successful dignity-conserving care, and (4) difficulties and barriers to the delivery of dignity-conserving care. Conclusions: Fidelity and precursory factors that enhance the beneficial effects of family-oriented dignity therapy were identified. Reinforcement strategies, such as using supplementary video, audio, and reading materials; developing a flexible approach to expressing feelings; and exploring lessons and achievements from various perspectives, are recommended for future research to enhance intervention effects. Trial registration: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1900020806).
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PURPOSE: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). DESIGN: Retrospective cohort study. METHODS: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005-2019. FINDINGS: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months' follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5-17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. CONCLUSION: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.
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Doença Relacionada a Imunoglobulina G4 , Doenças Orbitárias , Neoplasias Orbitárias , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/epidemiologia , Estudos Retrospectivos , Doenças Orbitárias/diagnóstico , Doenças Orbitárias/epidemiologia , Imunoglobulina GRESUMO
BACKGROUND: Enhancing patients' sense of dignity is the core element of high-quality palliative care. In Western countries, dignity therapy has shown promising positive effects on the sense of dignity and end-of-life experience. To apply this therapy in Chinese patients, a theory-driven, culturally relevant family-oriented dignity therapy was developed, guided by the Medical Research Council framework for complex intervention development. OBJECTIVES: This study examined the effectiveness of family-oriented dignity therapy in improving dignity-related distress, depression, and spiritual well-being in Chinese patients with lung cancer undergoing chemotherapy. DESIGN: A randomised controlled trial. SETTINGS AND METHODS: Patients who were diagnosed with lung cancer and undergoing chemotherapy were recruited using convenience sampling from a cancer hospital in Changsha, China. A significant family caregiver of each patient was invited to participate. Patients who met the inclusion criteria and agreed to participate (N = 120) were randomly assigned to receive family-oriented dignity therapy (intervention group, n = 60) or attention (control group, n = 60). The Patient Dignity Inventory, Patient Health Questionnaire-9, and Functional Assessment of Chronic Illness Therapy - Spiritual Well-being Scale were used to assess dignity-related distress, depression, and spiritual well-being, respectively, at baseline and 1- and 4-week follow-up. A generalised estimating equation was used to analyse the intervention effects across the time points. RESULTS: Compared with the control group, the patients in the intervention group showed significantly greater reduction in existential distress (ß: -1.372, 95% CI: -2.269, -0.472; p = 0.003) and depression (ß: -3.430, 95% CI: -5.032, -1.829; p < 0.001) at week one, as well as significantly greater improvement in spiritual well-being at both week one (ß: 3.705, 95% CI: 0.599, 6.811; p = 0.019) and week four (ß: 4.939, 95% CI: 0.476, 9.401; p = 0.030). CONCLUSIONS: Family-oriented dignity therapy has the potential to relieve existential distress and depressive symptoms and improve spiritual well-being. We expect our finding to impact research on family-oriented dignity therapy and enhance its effectiveness. We may also have an impact on nursing practice by providing a means to initiate conversations between nurses and the patients and family caregivers to relieve the psychosocial distress of patients during treatment. This study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1900020806).
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Neoplasias Pulmonares , Neoplasias , Depressão/terapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Cuidados Paliativos , Qualidade de Vida/psicologia , RespeitoRESUMO
BACKGROUND: International guidelines on clinical staging of gastric cancer recommend the use of chest CT for the detection of pulmonary metastases. This study assessed the clinical value of routine chest CT in the staging of gastric cancer. METHODS: This retrospective study included patients identified from the gastric cancer registry of Chang Gung Memorial Hospital, Linkou, Taiwan. All patients who underwent clinical staging between 2008 and 2014 were included. The pattern, site and number of metastases at initial presentation and after surgery with curative intent were evaluated. Pulmonary metastases were defined as multiple small round pulmonary nodules with a random distribution or of variable size. RESULTS: Some 1669 patients were included, of whom 478 (28·6 per cent) had metastatic disease at clinical presentation. The majority of metastases were to the peritoneum (75·7 per cent of patients) or liver (30·5 per cent), and only 27 patients (5·6 per cent) had pulmonary metastases at presentation, none of which were isolated to the lung. Of these 27 patients, 11 had primary lesions located at the cardia/fundus. In 19 patients the lung metastases were also detected on the staging chest X-ray. After surgery there were 196 cancer recurrences. Some 15 patients (7·6 per cent) had lung metastasis and this was not the only site of metastases in any patient. The prevalence of lung metastasis at presentation of the disease and after surgery was 1·6 and 1·5 per cent respectively. CONCLUSION: This study does not support the routine use of chest CT for staging of gastric cancer as isolated pulmonary metastasis in the absence of other metastatic sites could not be detected.
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Estadiamento de Neoplasias/métodos , Neoplasias Gástricas/diagnóstico por imagem , Idoso , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/secundário , Radiografia Torácica , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios XRESUMO
Acquired radial clubhand deformity can be a consequence of large bone gap left by premature extensive radius osteomyelitis sequestrectomy. Single-bone forearm reconstruction is a salvage procedure when other motion-preserving techniques are not feasible. Here we present a child who developed radial clubhand deformity after an untimely sequestrectomy of radius diaphysis. In view of limited microsurgical expertise in our centre, single-bone forearm procedure was done utilising simple Kirshner wires to achieve radio-ulnar fusion. The procedure resulted in pain-free stable wrist, restoration of hand function and improved cosmesis.
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Antivirais/uso terapêutico , Micose Fungoide/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Valaciclovir/uso terapêutico , Idoso , Feminino , Herpes Zoster/tratamento farmacológico , Humanos , Quimioterapia de Manutenção , Micose Fungoide/virologia , Indução de Remissão , Neoplasias Cutâneas/virologiaRESUMO
The sympathetic division of the autonomic nervous system includes a variety of cells including neurons, endocrine cells and glial cells. A recent study (Furlan et al. 2017) has revised thinking about the developmental origin of these cells. It now appears that sympathetic neurons and chromaffin cells of the adrenal medulla do not have an immediate common ancestor in the form a "sympathoadrenal cell", as has been long believed. Instead, chromaffin cells arise from Schwann cell precursors. This review integrates the new findings with the expanding body of knowledge on the signalling pathways and transcription factors that regulate the origin of cells of the sympathetic division of the autonomic nervous system.
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Transdução de Sinais , Sistema Nervoso Simpático/citologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cromafins/citologia , Células Cromafins/metabolismo , Humanos , Crista Neural/citologia , Crista Neural/metabolismoRESUMO
PURPOSE AND METHODS: Femoral hernia repairs have been done classically with three different open approaches, namely the Lockwood's (LW), Lotheissen's (LT) and McEvedy's (ME) approaches. Current literature has yet provided any definite conclusion over the best approach in emergency situations. This study aims to evaluate and compare the operative outcomes of these three approaches in emergency situations by retrospectively analyzing 190 cases (76 ME, 33 LT, 81 LW) in 13 years at a regional surgical center. RESULTS: Significantly less laparotomies were required for McEvedy's approach (ME 2.6% vs LT 33.3% vs LW 43.2%, p < 0.001), despite the need for bowel resection appear to be higher (ME 43.4% vs LT 27.3% vs LW 27.2%, p = 0.072). Overall hernia recurrence (p = 0.657) and surgical complication rates (p = 0.585) were similar between the three approaches. Although not reaching statistical significance, it appeared that in patients undergoing McEvedy's operation, mean length of stay was longer (ME 10.1 days vs LT 7.4 days vs LW 9.2 days, p = 0.407) and required more operation time (ME 97.4 min vs LT 72.0 min vs LW 79.0 min, p = 0.222). CONCLUSIONS: All three approaches were safe and effective in repairing femoral hernias in the emergency setting. McEvedy's approach may be superior to others when entry into the peritoneum is anticipated, although it may potentially be associated with longer operation time and hospital stay.
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Hérnia Femoral/cirurgia , Herniorrafia/métodos , Idoso , Idoso de 80 Anos ou mais , Tratamento de Emergência , Feminino , Humanos , Laparotomia , Masculino , Peritônio/cirurgia , Estudos RetrospectivosRESUMO
The nonlinear phenomena that occur in the electric double layer (EDL) that forms at charged surfaces strongly influence electrokinetic effects, including electro-osmosis and electrophoresis. In particular, saturation effects due to either dielectric decrement or ion crowding effects are of paramount importance. Dielectric decrement significantly influences the ionic concentration in the EDL at high ζ potential, leading to the formation of a condensed layer near the particle's surface. In this article, we present a model incorporating both steric effects due to the finite size of ions and dielectric decrement to describe the physics in the electric double layer. The model remains valid in both weakly and strongly nonlinear regimes, as long as the electric double layer remains in quasiequilibrium. We apply this model to the study of two archetypal problems in electrokinetics, namely the electrophoresis of particles with fixed surface charges and the electrophoresis of ideally polarizable particles.
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BACKGROUND: Simulation training in endovascular surgery provides opportunities for trainees to practice and learn from non-patient based experience. Several types of endovascular simulators are available commercially. Previous studies on endovascular simulation training can be categorized into trials in which only a simulator was used when measuring performance metrics or "trials within simulation"; patient specific procedure rehearsals; and randomized, controlled trials (RCTs) or translational studies. OBJECTIVES: To examine whether endovascular simulation training can improve surgeon techniques and patient outcomes in real clinical settings. METHODS: A literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All searches were done via PubMed and Embase. Review articles, and papers that were not related to endovascular surgery and not within the scope of interest were excluded. References of review articles were further screened according to the exclusion criteria. RESULTS: In total, 909 records were identified and 290 duplicates were removed. Thirty-one were included in the qualitative analysis. Twenty-three were trials within simulation and most of them found statistically significant improvements in procedure time, fluoroscopy time, and contrast volume. Five were patient specific procedure rehearsals and showed that simulation significantly affected the fluoroscopy angle and improved performance metrics. Three were RCTs and revealed mainly positive results on a Global Rating Scale and procedure specific rating scale. CONCLUSIONS: Contemporary evidence shows that performance metrics within endovascular simulations improve with simulation training. Successful translation to in vivo situations is observed in patient specific procedure rehearsals and RCTs on real procedures. However, there is no level I evidence to show that predictive validity of simulation can definitively improve patient outcomes. Current literature supports the idea that there is a beneficial role of simulation in endovascular training. Future studies are needed to confirm the efficacy of simulation in endovascular surgical training and to see if simulation is superior to traditional training in the operating theatre.
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Simulação por Computador , Educação Médica Continuada/métodos , Procedimentos Endovasculares/educação , Competência Clínica , HumanosRESUMO
Rat liver regeneration (RLR) induced by partial hepatectomy involves cell proliferation regulated by numerous factors, including microRNAs (miRNAs). miRNA high-throughput sequencing has been established and used to analyze miRNA expression profiles. This study showed that 39 miRNAs were related to RLR through the analysis of miRNA high-throughput sequencing. Their role toward rat normal hepatocyte line BRL-3A was studied by gain- and loss-of-function analyses, and one of them, microRNA-21 (miR-21), obviously upregulated and promoted BRL-3A cell proliferation. Using bioinformatics to search for miR-21 targets revealed that Fas ligand (FASLG) is one of miR-21's target genes. A dual-luciferase report assay and Western blot assay showed that miR-21 directly targeted the 3'-untranslated region of FASLG and inhibited the expression of FASLG, which suggests that miR-21 promoted BRL-3A cell proliferation by reducing FASLG expression.
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Regiões 3' não Traduzidas/genética , Proliferação de Células/genética , Proteína Ligante Fas/genética , Proteína Ligante Fas/metabolismo , MicroRNAs/genética , Animais , Apoptose/genética , Sequência de Bases , Linhagem Celular , Hepatectomia , Hepatócitos/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Regeneração Hepática/fisiologia , Ratos , Ratos Sprague-Dawley , Análise de Sequência de DNARESUMO
BACKGROUND: Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) has been shown by several retrospective studies to be technically feasible and associated with favorable outcomes when compared to the open approach. This study aims to mitigate potential selection bias by performing a case control study of laparoscopic (LWR) versus open wedge resection (OWR) matched by resection type, location and tumor size. METHODS: We retrospectively identified 50 consecutive patients who underwent LWR for a suspected gastric GIST from a prospective database and matched this cohort with 50 patients who underwent OWR. RESULTS: There was no statistical difference between the key baseline clinicopathological features of patients' who underwent LWR versus OWR. Patients who underwent LWR had longer operating times [150 (range, 65-270) minutes vs 92.5 (25-200) minutes, P < .001] but decreased median blood loss [0 (0-300) ml vs 0 (0-1200) ml, P = .015], decreased frequency of intraoperative or postoperative blood transfusion [1 (2%) vs 8 (16%), P = .031], decreased median time to liquid diet [2 (0-5) vs 3 (1-7) days, P < .001], decreased median time to solid diet [3 (1-6) vs 5 (2-11) days, P < .001] and decreased postoperative stay [4 (2-10) vs 4.5 (3-17), P < .001] compared to OWR. There was no difference in oncological outcomes such as frequency of close margins (≤ 1 mm) and recurrence-free survival. CONCLUSION: This matched case-control study provides supporting evidence that LWR results in superior perioperative outcomes compared to OWR without compromising on oncological outcomes.
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Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Laparoscopia , Laparotomia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Estudos de Casos e Controles , Ingestão de Alimentos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Nonradiative energy transfer from an InGaN quantum well to Ag nanoparticles is unambiguously demonstrated by the time-resolved photoluminescence. The distance dependence of the energy transfer rate is found to be proportional to 1/d(3), in good agreement with the prediction of the dipole interaction calculated from the Joule losses in acceptors. The maximum energy-transfer efficiency of this energy transfer system can be as high as 83%.