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991.
Sebastian F. Maehrlein Prakriti P. Joshi Lucas Huber Feifan Wang Marie Cherasse Yufeng Liu Dominik M. Juraschek Edoardo Mosconi Daniele Meggiolaro Filippo De Angelis X.-Y. Zhu 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(7)
The ultrafast polarization response to incident light and ensuing exciton/carrier generation are essential to outstanding optoelectronic properties of lead halide perovskites (LHPs). A large number of mechanistic studies in the LHP field to date have focused on contributions to polarizability from organic cations and the highly polarizable inorganic lattice. For a comprehensive understanding of the ultrafast polarization response, we must additionally account for the nearly instantaneous hyperpolarizability response to the propagating light field itself. While light propagation is pivotal to optoelectronics and photonics, little is known about this in LHPs in the vicinity of the bandgap where stimulated emission, polariton condensation, superfluorescence, and photon recycling may take place. Here we develop two-dimensional optical Kerr effect (2D-OKE) spectroscopy to energetically dissect broadband light propagation and dispersive nonlinear polarization responses in LHPs. In contrast to earlier interpretations, the below-bandgap OKE responses in both hybrid CH3NH3PbBr3 and all-inorganic CsPbBr3 perovskites are found to originate from strong hyperpolarizability and highly anisotropic dispersions. In both materials, the nonlinear mixing of anisotropically propagating light fields results in convoluted oscillatory polarization dynamics. Based on a four-wave mixing model, we quantitatively derive dispersion anisotropies, reproduce 2D-OKE frequency correlations, and establish polarization-dressed light propagation in single-crystal LHPs. Moreover, our findings highlight the importance of distinguishing the often-neglected anisotropic light propagation from underlying coherent quasiparticle responses in various forms of ultrafast spectroscopy.Understanding the ultrafast polarization response to light fields and the subsequent generation of charge carriers or excitons is key to establishing the photophysical mechanisms in the excellent optoelectronic material system of lead halide perovskites (LHPs) (1). The two ionic polarization contributions by the reorientational motion of organic cations and the deformation of the inorganic cages have been discussed within dynamic screening models (2–4) and large polaron formation (5), respectively and jointly, whereas the immediate electronic polarization response to the light field itself has been neglected so far. In many optoelectronic applications, nevertheless, not only charge carrier transport but also light propagation right below the bandgap is essential. In LHP nanowire lasers, the lasing modes are known to be redshifted from excitonic resonances due to efficient coupling to plasmon emission (6). In LHP-based exciton–polariton devices, light–matter coupling redshifts the hybrid state on the lower polariton branch (7). Propagation of subgap light is known to boost the efficiency of LHP photovoltaic cells and light-emitting devices by the so-called “photon recycling” (8). Light propagation strongly influences the function of LHP photonic devices in general (9, 10). A key feature of light propagation near the bandgap is its strong photon energy dependence, as is obvious from the classic Lorentzian model for the dielectric function near an optical resonance (11). However, most photophysical experiments probing carrier/exciton formation, screening, scattering, and nonlinear optical responses employ ultrashort excitation pulses with inherently broad energy distribution and thus convoluted spectral responses. Here, we develop a Fourier-transform-based laser spectroscopy technique, two-dimensional optical Kerr effect (2D-OKE), to investigate light propagation and nonlinear polarization responses directly in the time domain with superior excitation energy resolution near the electronic bandgap.The third-order nonlinear electric polarization serves as an in situ probe of a material’s polarizability and governs the ultrafast macroscopic response to an incident light field. This is employed in a variety of spectroscopies, such as (magneto-) OKE (12, 13), coherent phonon spectroscopy (14, 15), and four-wave mixing (FWM) in general (11). Recently, OKE has been applied to LHP single crystals: Below the bandgap, the dominating nonoscillatory Kerr response of MAPbBr3 (MA = CH3NH3) compared to its all-inorganic counterpart CsPbBr3 was previously attributed to the transient polarization anisotropy caused by liquidlike reorientation dynamics of organic cations (2) and lattice disorder (5). The exponentially decaying responses with above-gap excitations were discussed in relation to polaron formation in both materials (5). Interestingly, for excitation energies close to the bandgap in CsPbBr3 at room temperature, time-resolved OKE reveals complex oscillatory features. Such oscillatory transient birefringence signals are usually attributed to coherently excited collective modes, such as phonons (15–17) or magnons (18, 19), but the strong dependence of the oscillatory frequency on pump-photon energy in OKE seems to contradict these origins in LHPs (5). In this work, we unveil a unified source for the Kerr responses in single-crystal LHPs by tracing contributions from hyperpolarizability and the peculiar light propagation close to electronic transitions. 相似文献
992.
PURPOSE OF REVIEW: Efficacious pharmacologic treatments are available for the management of hypertension, yet only about 50% of patients treated with antihypertensive medications have their blood pressure controlled. A key factor contributing to poor blood pressure control is suboptimal adherence to prescribed therapy. Despite numerous studies conducted over the last 50 years to identify the best method for increasing patient compliance, no single intervention has emerged as superior to the others. This article reviews the effectiveness of methods to improve antihypertensive medication adherence, discusses the effect of drug benefit caps on compliance, and proposes a framework for future clinical and research directions. RECENT FINDINGS: Several recent systematic reviews and meta-analyses have attempted to quantify the effectiveness of various methods to improve adherence. As a result of the multiple factors influencing medication adherence, a patient-centered approach that tailors interventions aimed at overcoming barriers to adherence may be necessary. SUMMARY: Physicians and other health care professionals should consider nonadherence to medication when evaluating a patient with poor blood pressure control. In selecting an intervention to improve compliance to medications, clinicians should consider engaging the patient in an intervention that overcomes patient-specific barriers. Future research should target development of adherence models, which simultaneously examine the effects and interactions of social, psychological, and biologic variables on antihypertensive medication adherence. 相似文献
993.
Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects 总被引:3,自引:0,他引:3
Qing M Schumacher K Heise R Wöltje M Vazquez-Jimenez JF Richter T Arranda-Carrero M Hess J von Bernuth G Seghaye MC 《Journal of the American College of Cardiology》2003,41(12):2266-2274
OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium. METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively. RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD. CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant's myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group. 相似文献
994.
Deenik W van der Holt B Verhoef GE Smit WM Kersten MJ Kluin-Nelemans HC Verdonck LF Ferrant A Schattenberg AV Janssen JJ Sonneveld P van Marwijk Kooy M Wittebol S Willemze R Wijermans PW Westveer PH Beverloo HB Valk P Löwenberg B Ossenkoppele GJ Cornelissen JJ 《Blood》2008,111(5):2581-2588
The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic-phase chronic myeloid leukemia (CML). Patients received 2 cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1-7) in conjunction with imatinib (200 mg, 400 mg, 600 mg, or 800 mg), according to predefined, successive dose levels. All dose levels proved feasible. Seven dose-limiting toxicities (DLTs) were observed in 302 cycles of chemotherapy, which were caused by streptococcal bacteremia in 5 cases. Intermediate-dose cytarabine (1000 mg/m(2)) prolonged time to neutrophil recovery and platelet recovery compared with a standard dose (200 mg/m(2)). High-dose imatinib (600 mg or 800 mg) extended the time to platelet recovery compared with a standard dose (400 mg). More infectious complications common toxicity criteria (CTC) grade 3 or 4 were observed after intermediate-dose cytarabine compared with a standard-dose of cytarabine. Early response data after combination therapy included a complete cytogenetic response in 48% and a major molecular response in 30% of patients, which increased to 46% major molecular responses at 1 year, including 13% complete molecular responses. We conclude that combination therapy of escalating dosages of imatinib and cytarabine is feasible. This study was registered at www.kankerbestrijding.nl as no. CKTO-2001-03. 相似文献
995.
Gürlich R Maruna P Kalvach Z Peskova M Cermak J Frasko R 《Archives of gerontology and geriatrics》2005,41(2):183-190
Colorectal cancer is predominantly a disease of elderly people, since over 70% of cases occur in those aged 65 years or older. Clinicians have to frequently decide whether major surgery is justified in elderly patients with a limited life expectancy. Our retrospective study was aimed to compare outcomes of primary surgery for colorectal cancer in the elderly patient population. The evaluated data were collected from the 1st Department of Surgery, Charles University, and from all over the Czech Republic. Patients were divided into three groups: the young-old (21-59 years), the older-old (60-69 years), and the oldest-old (>69 years) patients. In the collective data the youngest and the oldest groups differ significantly in the rate of early postoperative complications (12.3% versus 17.6%, p<0.001). The number of complications associated with the emergency procedures was twice as high compared to elective surgery in all groups (p<0.001). There was no correlation between age and length of hospital stay in the single surgery department. These data suggest that major oncology procedures may be undertaken in older patients in whom operative risk is reasonable, with acceptable rates of complications. 相似文献
996.
Link K Moëll C Garwicz S Cavallin-Ståhl E Björk J Thilén U Ahrén B Erfurth EM 《The Journal of clinical endocrinology and metabolism》2004,89(10):5003-5012
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and until recently prophylactic cranial radiotherapy (CRT) was important for achieving long-term survival. Hypothalamic-pituitary hormone insufficiency is a well-recognized consequence of CRT for childhood cancer. Another problem is increased cardiovascular risk, which has been shown in long-term survivors of other childhood cancers. In the only previously reported study on cardiovascular risk after childhood ALL, obesity and dyslipidemia were recorded in a small subgroup treated with CRT, compared with patients treated with chemotherapy. The mechanisms behind the increase in cardiovascular risk in survivors of childhood cancer are not clarified.The aim of the present study was to elucidate mechanisms of increased cardiovascular risk in former childhood ALL patients. A group of 44 ALL survivors (23 males, median age 25 yr, range 19-32 yr at the time of study) treated with CRT (median 24 Gy, 18-30 Gy) at a median age of 5 yr (1-18 yr) and chemotherapy were investigated for prevalence of GH deficiency and cardiovascular risk factors. Comparison was made with controls randomly selected from the general population and individually matched for sex, age, smoking habits, and residence. All patients and controls underwent a GHRH-arginine test, and patients with a peak GH 3.9 microg/liter or greater were further investigated with an additional insulin tolerance test.Significantly higher plasma levels of insulin (P = 0.002), blood glucose (P = 0.01), and serum levels of low-density lipoprotein cholesterol, apolipoprotein (Apo) B, triglycerides, fibrinogen, and leptin (all P 相似文献
997.
Andrès E Maloisel F Kurtz JE Kaltenbach G Alt M Weber JC Sibilia J Schlienger JL Blicklé JF Brogard JM Dufour P 《European Journal of Internal Medicine》2002,13(5):324-328
BACKGROUND: The present study reports a monocentric experience of 90 drug-induced agranulocytosis cases and discusses their management, in particular the role of hematopoietic growth factors. METHODS: Data from 90 patients with drug-induced agranulocytosis who met the criteria of the IAAAS group and of Bénichou and Solal-Celigny [Nouv Rev Fr Hematol 1993; 33: 257.] were retrospectively reviewed. All cases were extracted from a cohort study of the Hopitaux Universitaires de Strasbourg, France. Data were specifically analyzed with regard to the use of hematopoietic growth factors (in 42 patients). RESULTS: Mean patient age was 63 (range 17-95) years and the sex ratio (M/F) was 0.39. An underlying disease was present in 37% of the patients. Antibiotics (25%), antithyroid drugs (23%), and antiaggregative platelet agents (16%) were the most frequent causative drugs. Main clinical features included isolated fever (41%), septicemia or septic shock (31%), and pneumonia (10%). Mean neutrophil count was 0.13 (range 0-0.46)x10(9)/l. Outcome was favorable in 98% of patients. The mean durations of hematological recovery (neutrophil count over 1.5x10(9)/l), antibiotic therapy, and hospitalization was 8.5 (range 2-21) days, 9.2 (range 2-21) days, and 10.5 (range 3-23) days, respectively. All patients were treated with broad-spectrum antibiotics and 42 patients with hematopoietic growth factors. In these 42 patients, the mean durations for hematological recovery, antibiotic therapy, and hospitalization were significantly reduced at: 6.3 (range 2-16) days, 7.1 (range 2-16) days, and 9.1 (range 3-23) days, respectively (all P<0.05). CONCLUSIONS: The present study shows that new causative drugs are emerging (antibiotics, antithyroid, and antiaggregative platelet agents), that drug-induced agranulocytosis remains typically a serious accident with severe sepsis, and that modern management with broad spectrum antibiotics and hematopoietic growth factors may reduce the mortality. 相似文献
998.
Amplification of low-frequency antiviral CD8 T cell responses using autologous dendritic cells. 总被引:5,自引:0,他引:5
Marie Larsson David T Wilkens Jean-Fran?ois Fonteneau Thomas J Beadle Melissa J Merritt Rhonda G Kost Patrick A J Haslett Susan Cu-Uvin Nina Bhardwaj Douglas F Nixon Barbara L Shacklett 《AIDS (London, England)》2002,16(2):171-180
OBJECTIVE: To utilize the potent antigen-presenting capacity of mature dendritic cells (MDC) in order to develop a rapid, sensitive method for quantifying antigen-specific CD8 T cells present at low frequency in peripheral blood. DESIGN: Peripheral blood mononuclear cells (PBMC) were obtained from seven HIV-1-positive individuals with low to moderate CD8 T cell responses, including five on highly active antiretroviral therapy (HAART). IFN-gamma ELISPOT assays were performed using either monocytes or MDC to present antigens expressed by recombinant vaccinia viruses (r-VV). METHODS: Peripheral blood-derived monocytes were cultured for 5-6 days in the presence of IL-4 and granulocyte macrophage colony-stimulating factor, then matured in monocyte-conditioned medium. MDC were infected with r-VV and co-cultured in an ELISPOT assay with autologous monocyte-depleted PBMC. RESULTS: Relative to autologous monocytes, MDC amplified detection of antigen-specific CD8 T cells by 2-30-fold in response to antigens from HIV-1, Epstein-Barr virus and cytomegalovirus. Furthermore, antigenic specificities were revealed that had not been detected using standard ELISPOT of PBMC. CONCLUSION: This assay will prove useful for the detection of memory T cells present at low frequency, and may be of interest for identifying subdominant cytotoxic T lymphocyte epitopes. This method may have broad applications for the detection of antiviral CD8 T cell responses in patient populations in whom such responses have been difficult to detect, including HIV-1-seropositive individuals with advanced disease or undergoing HAART. 相似文献
999.
Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus 总被引:7,自引:0,他引:7
Larsson M Fonteneau JF Lirvall M Haslett P Lifson JD Bhardwaj N 《AIDS (London, England)》2002,16(10):1319-1329
BACKGROUND: The CD4 T cells in mucosal subepithelia are the first cells to become infected during sexual transmission of HIV-1. Dendritic cells (DC) are located in the same area and are known to play a central role in antiviral immune responses. However, extensive viral replication, syncytia formation and cell death follows the interaction between T cells and DC previously exposed to HIV-1. Despite this, anti-HIV responses are generated that control viremia following acute infection. OBJECTIVE: The anti-HIV-1 cellular immune responses observed may be activated by sources other than productively infected DC. HIV-1 induces apoptosis both in cells it infects and in bystander cells. Furthermore, retroviral replication typically generates a predominance of defective particles. We tested whether DC exposed to antigen from either of these sources could elicit anti-HIV specific immune responses. DESIGN AND METHODS: Apoptotic or necrotic monocytes infected with vaccinia virus vectors encoding HIV antigens, a cell line with integrated HIV-1 and apoptotic CD4 T cells pulsed with non-infectious or infectious HIV-1 virus were used as sources of antigens to assess cross presentation by DC. Furthermore, direct DC presentation of antigen from non-infectious and infectious HIV-1 was examined. RESULTS: We find that dead cells expressing HIV-1 antigens as well as non-infectious HIV-1 particles can be acquired and processed by DC, leading to the activation, differentiation and expansion of viral antigen-specific CD4 and CD8 T cells from seropositive individuals. CONCLUSIONS: These sources of antigens may be critical for the generation and maintenance of anti-HIV-1 immunity by DC. 相似文献