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1.
Nat Nanotechnol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077963

RESUMO

Many nanoscale devices require precise optimization to function. Tuning them to the desired operation regime becomes increasingly difficult and time-consuming when the number of terminals and couplings grows. Imperfections and device-to-device variations hinder optimization that uses physics-based models. Deep neural networks (DNNs) can model various complex physical phenomena but, so far, are mainly used as predictive tools. Here, we propose a generic deep-learning approach to efficiently optimize complex, multi-terminal nanoelectronic devices for desired functionality. We demonstrate our approach for realizing functionality in a disordered network of dopant atoms in silicon. We model the input-output characteristics of the device with a DNN, and subsequently optimize control parameters in the DNN model through gradient descent to realize various classification tasks. When the corresponding control settings are applied to the physical device, the resulting functionality is as predicted by the DNN model. We expect our approach to contribute to fast, in situ optimization of complex (quantum) nanoelectronic devices.

2.
Nat Commun ; 11(1): 1292, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157092

RESUMO

Exciton management in organic light-emitting diodes (OLEDs) is vital for improving efficiency, reducing device aging, and creating new device architectures. In particular in white OLEDs, exothermic Förster-type exciton transfer, e.g. from blue to red emitters, plays a crucial role. It is known that a small exothermicity partially overcomes the spectral Stokes shift, enhancing the fraction of resonant donor-acceptor pair states and thus the Förster transfer rate. We demonstrate here a second enhancement mechanism, setting in when the exothermicity exceeds the Stokes shift: transfer to multiple higher-lying electronically excited states of the acceptor molecules. Using a recently developed computational method we evaluate the Förster transfer rate for 84 different donor-acceptor pairs of phosphorescent emitters. As a result of the enhancement the Förster radius tends to increase with increasing exothermicity, from around 1 nm to almost 4 nm. The enhancement becomes particularly strong when the excited states have a large spin-singlet character.

3.
Nano Lett ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32091910

RESUMO

According to Fourier's law, a temperature difference across a material results in a linear temperature profile and a thermal conductance that decreases inversely proportional to the system length. These are the hallmarks of diffusive heat flow. Here, we report heat flow in ultrathin (25 nm) GaP nanowires in the absence of a temperature gradient within the wire and find that the heat conductance is independent of wire length. These observations deviate from Fourier's law and are direct proof of ballistic heat flow, persisting for wire lengths up to at least 15 µm at room temperature. When doubling the wire diameter, a remarkably sudden transition to diffusive heat flow is observed. The ballistic heat flow in the ultrathin wires can be modeled within Landauer's formalism by ballistic phonons with an extraordinarily long mean free path.

4.
Nature ; 577(7790): 341-345, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942054

RESUMO

Classification is an important task at which both biological and artificial neural networks excel1,2. In machine learning, nonlinear projection into a high-dimensional feature space can make data linearly separable3,4, simplifying the classification of complex features. Such nonlinear projections are computationally expensive in conventional computers. A promising approach is to exploit physical materials systems that perform this nonlinear projection intrinsically, because of their high computational density5, inherent parallelism and energy efficiency6,7. However, existing approaches either rely on the systems' time dynamics, which requires sequential data processing and therefore hinders parallel computation5,6,8, or employ large materials systems that are difficult to scale up7. Here we use a parallel, nanoscale approach inspired by filters in the brain1 and artificial neural networks2 to perform nonlinear classification and feature extraction. We exploit the nonlinearity of hopping conduction9-11 through an electrically tunable network of boron dopant atoms in silicon, reconfiguring the network through artificial evolution to realize different computational functions. We first solve the canonical two-input binary classification problem, realizing all Boolean logic gates12 up to room temperature, demonstrating nonlinear classification with the nanomaterial system. We then evolve our dopant network to realize feature filters2 that can perform four-input binary classification on the Modified National Institute of Standards and Technology handwritten digit database. Implementation of our material-based filters substantially improves the classification accuracy over that of a linear classifier directly applied to the original data13. Our results establish a paradigm of silicon-based electronics for small-footprint and energy-efficient computation14.

5.
Eur Heart J ; 40(40): 3318-3332, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31004144

RESUMO

AIMS: Heart failure with preserved ejection fraction (HFpEF) and pathological cardiac aging share a complex pathophysiology, including extracellular matrix remodelling (EMR). Protease-activated receptor 2 (PAR2) deficiency is associated with EMR. The roles of PAR1 and PAR2 have not been studied in HFpEF, age-dependent cardiac fibrosis, or diastolic dysfunction (DD). METHODS AND RESULTS: Evaluation of endomyocardial biopsies from patients with HFpEF (n = 14) revealed that a reduced cardiac PAR2 expression was associated with aggravated DD and increased myocardial fibrosis (r = -0.7336, P = 0.0028). In line, 1-year-old PAR2-knockout (PAR2ko) mice suffered from DD with preserved systolic function, associated with an increased age-dependent α-smooth muscle actin expression, collagen deposition (1.7-fold increase, P = 0.0003), lysyl oxidase activity, collagen cross-linking (2.2-fold increase, P = 0.0008), endothelial activation, and inflammation. In the absence of PAR2, the receptor-regulating protein caveolin-1 was down-regulated, contributing to an augmented profibrotic PAR1 and transforming growth factor beta (TGF-ß)-dependent signalling. This enhanced TGF-ß/PAR1 signalling caused N-proteinase (ADAMTS3) and C-proteinase (BMP1)-related increased collagen I production from cardiac fibroblasts (CFs). PAR2 overexpression in PAR2ko CFs reversed these effects. The treatment with the PAR1 antagonist, vorapaxar, reduced cardiac fibrosis by 44% (P = 0.03) and reduced inflammation in a metabolic disease model (apolipoprotein E-ko mice). Patients with HFpEF with upstream PAR inhibition via FXa inhibitors (n = 40) also exhibited reduced circulating markers of fibrosis and DD compared with patients treated with vitamin K antagonists (n = 20). CONCLUSIONS: Protease-activated receptor 2 is an important regulator of profibrotic PAR1 and TGF-ß signalling in the heart. Modulation of the FXa/FIIa-PAR1/PAR2/TGF-ß-axis might be a promising therapeutic approach to reduce HFpEF.

6.
J Phys Chem Lett ; 10(6): 1374-1381, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30829040

RESUMO

We employed bias-assisted charge extraction techniques to investigate the transient and steady-state recombination of photogenerated charge carriers in complete devices of a disordered polymer-fullerene blend. Charge recombination is shown to be dispersive, with a significant slowdown of the recombination rate over time, consistent with the results from kinetic Monte Carlo simulations. Surprisingly, our experiments reveal little to no contributions from early time recombination of nonequilibrated charge carriers to the steady-state recombination properties. We conclude that energetic relaxation of photogenerated carriers outpaces any significant nongeminate recombination under application-relevant illumination conditions. With equilibrated charges dominating the steady-state recombination, quasi-equilibrium concepts appear suited for describing the open-circuit voltage of organic solar cells despite pronounced energetic disorder.

7.
J Phys Chem C Nanomater Interfaces ; 122(31): 17660-17667, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30116464

RESUMO

Because of its thermal stability, lead-free composition, and nearly ideal optical and electronic properties, the orthorhombic CsSnI3 perovskite is considered promising as a light absorber for lead-free all-inorganic perovskite solar cells. However, the susceptibility of this three-dimensional perovskite toward oxidation in air has limited the development of solar cells based on this material. Here, we report the findings of a computational study which identifies promising Rb y Cs1-y Sn(Br x I1-x )3 perovskites for solar cell applications, prepared by substituting cations (Rb for Cs) and anions (Br for I) in CsSnI3. We show the evolution of the material electronic structure as well as its thermal and structural stabilities upon gradual substitution. Importantly, we demonstrate how the unwanted yellow phase can be suppressed by substituting Br for I in CsSn(Br x I1-x )3 with x ≥ 1/3. We predict that substitution of Rb for Cs results in a highly homogeneous solid solution and therefore an improved film quality and applicability in solar cell devices.

8.
Adv Mater ; 30(26): e1707350, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29736912

RESUMO

Recent success in achieving highly stable Rb-containing organolead halide perovskites has indicated the possibility of incorporating small monovalent cations, which cannot fit in the lead-halide cage with an appropriate tolerance factor, into the perovskite lattice while maintaining a pure stable "black" phase. In this study, through a combined experimental and theoretical investigation by density functional theory (DFT) calculations on the incorporation of extrinsic alkali cations (Rb+ , K+ , Na+ , and Li+ ) in perovskite materials, the size-dependent interstitial occupancy of these cations in the perovskite lattice is unambiguously revealed. Interestingly, DFT calculations predict the increased ion migration barriers in the lattice after the interstitial occupancy. To verify this prediction, ion migration behavior is characterized through hysteresis analysis of solar cells, electrical poling, temperature-dependent conductivity, and time-dependent photoluminescence measurements. The results collectively point to the suppression of ion migration after lattice interstitial occupancy by extrinsic alkali cations. The findings of this study provide new material design principles to manipulate the structural and ionic properties of multication perovskite materials.

9.
Sci Rep ; 7(1): 14386, 2017 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-29084980

RESUMO

The outstanding optoelectronics and photovoltaic properties of metal halide perovskites, including high carrier motilities, low carrier recombination rates, and the tunable spectral absorption range are attributed to the unique electronic properties of these materials. While DFT provides reliable structures and stabilities of perovskites, it performs poorly in electronic structure prediction. The relativistic GW approximation has been demonstrated to be able to capture electronic structure accurately, but at an extremely high computational cost. Here we report efficient and accurate band gap calculations of halide metal perovskites by using the approximate quasiparticle DFT-1/2 method. Using AMX3 (A = CH3NH3, CH2NHCH2, Cs; M = Pb, Sn, X = I, Br, Cl) as demonstration, the influence of the crystal structure (cubic, tetragonal or orthorhombic), variation of ions (different A, M and X) and relativistic effects on the electronic structure are systematically studied and compared with experimental results. Our results show that the DFT-1/2 method yields accurate band gaps with the precision of the GW method with no more computational cost than standard DFT. This opens the possibility of accurate electronic structure prediction of sophisticated halide perovskite structures and new materials design for lead-free materials.

10.
Sci Rep ; 7: 41171, 2017 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-28117371

RESUMO

We report charge transport measurements in nanoscale vertical pillar structures incorporating ultrathin layers of the organic semiconductor poly(3-hexylthiophene) (P3HT). P3HT layers with thickness down to 5 nm are gently top-contacted using wedging transfer, yielding highly reproducible, robust nanoscale junctions carrying high current densities (up to 106 A/m2). Current-voltage data modeling demonstrates excellent hole injection. This work opens up the pathway towards nanoscale, ultrashort-channel organic transistors for high-frequency and high-current-density operation.

11.
Cardiovasc Revasc Med ; 17(3): 169-75, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27157293

RESUMO

BACKGROUND: The reactivity of platelets is increased in patients with peripheral artery disease (PAD). RANTES and sCD40L are chemokines which are stored in the alpha-granules of platelets. Clopidogrel inhibits and thus reduces platelet reactivity. Whether a treatment with clopidogrel is associated with an inhibition of systemic inflammation in patients with PAD has not been thoroughly explored. This study examined the effect of clopidogrel on platelet reactivation and the release of inflammatory chemokines in patients with PAD. METHODS: 40 patients with PAD were randomized into two groups. In the first group A the patients were treated with 100mg acetylsalicylic acid (ASA) and additional placebo for 4weeks. The patients in group B received 75mg/d clopidogrel in addition to ASA 100mg for 4weeks. After obtaining blood at days 0, 7 and 28 the platelet activation was determined by measuring the surface protein expression of CD63, CD62p and thrombospondin (TSP) after stimulation with TRAP and ADP. The release of the chemokines RANTES and sCD40L from platelets was analyzed by ELISA. RESULTS: Platelet activation markers (CD62p and CD63) and chemokine RANTES were significantly reduced in patients with PAD after 7 and 28days after treatment with clopidogrel. No alterations were found in TSP expression and sCD40L during the treatment. CONCLUSION: The treatment with clopidogrel leads to a reduction of platelet reactivity and release of RANTES from the platelets of patients with PAD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Plaquetas/efeitos dos fármacos , Inflamação/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/análogos & derivados , Anti-Inflamatórios/efeitos adversos , Aspirina/uso terapêutico , Biomarcadores/sangue , Plaquetas/metabolismo , Ligante de CD40/sangue , Quimiocina CCL5/sangue , Clopidogrel , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Alemanha , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Mediadores da Inflamação/sangue , Selectina-P/sangue , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/efeitos adversos , Testes de Função Plaquetária , Tetraspanina 30/sangue , Trombospondinas/sangue , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
12.
Phys Rev Lett ; 117(27): 276803, 2016 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-28084749

RESUMO

Charge transport in disordered organic semiconductors is generally described as a result of incoherent hopping between localized states. In this work, we focus on multicomponent emissive host-guest layers as used in organic light-emitting diodes (OLEDs), and show using multiscale ab initio based modeling that charge transport can be significantly enhanced by the coherent process of molecular superexchange. Superexchange increases the rate of emitter-to-emitter hopping, in particular if the emitter molecules act as relatively deep trap states, and allows for percolation path formation in charge transport at low guest concentrations.

13.
Cardiovasc Diabetol ; 14: 15, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25645908

RESUMO

BACKGROUND: Although antiplatelet therapy involving clopidogrel is a standard treatment for preventing cardiovascular events after coronary stent implantation, patients can display differential responses. Here, we assessed the effectiveness of clopidogrel on platelet function inhibition in subjects with and without type-2 diabetes and stable coronary artery disease. In addition, we investigated the correlation between platelet function and routine clinical parameters. METHODS: A total of 64 patients with stable coronary heart disease were enrolled in the study. Among these, 32 had known type-2 diabetes, whereas the remaining 32 subjects were non-diabetics (control group). A loading dose of 300 mg clopidogrel was given to clopidogrel-naïve patients (13 patients in the diabetes group and 14 control patients). All patients were given a daily maintenance dose of 75 mg clopidogrel. In addition, all patients received 100 mg ASA per day. Agonist-induced platelet aggregation measurements were performed on hirudin-anticoagulated blood using an impedance aggregometer (Multiple Platelet Function Analyzer, Dynabyte, Munich, Germany). Blood samples were drawn from the antecubital vein 24 h after coronary angiography with percutaneous coronary intervention. The platelets were then stimulated with ADP alone or ADP and prostaglandin-E (ADP and ADP-PGE tests, respectively) in order to evaluate clopidogrel-mediated inhibition of platelet function. The effectiveness of ASA was measured by stimulation with arachidonic acid (ASPI test). In addition, maximal platelet aggregation was assessed via stimulation with thrombin receptor-activating peptide (TRAP test). RESULTS: Patients with diabetes exhibited significantly less inhibition of platelet function than patients without diabetes (ADP-PGE test p = 0.003; ASPI test p = 0.022). Administering a clopidogrel loading dose of 300 mg did not result in a lower level of ADP-PGE-induced platelet reactivity in comparison to the use of a 75 mg maintenance dose. Moreover, we observed that ADP-PGE-induced platelet inhibition was positively correlated with fasting blood glucose and HbA1c (p < 0.01). CONCLUSIONS: Patients with type-2 diabetes exhibited increased platelet reactivity compared to patients without diabetes despite combined treatment with clopidogrel and ASA. Using a loading dose of clopidogrel rather than small daily doses was not sufficient for adequately overcoming increased platelet reactivity in patients with type-2 diabetes, highlighting the need for more effective anti-platelet drugs for such patients.


Assuntos
Plaquetas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/análogos & derivados , Idoso , Plaquetas/metabolismo , Clopidogrel , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ativação Plaquetária/fisiologia , Inibidores da Agregação de Plaquetas/farmacologia , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico , Resultado do Tratamento
14.
J Card Fail ; 21(4): 330-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25498756

RESUMO

BACKGROUND: Nicotinamide phosphoribosyltransferase (Nampt) is an enzyme involved in nicotinamide adenine dinucleotide biosynthesis. Nampt functions as gatekeeper of energy status and survival in cardiac myocytes in animal models of ischemia-reperfusion and might regulate inflammatory processes. Therefore, we performed for the 1st time a clinical study to determine the effects of Nampt on cardiac function in patients with nonischemic dilated (DCM) and inflammatory (DCMi) cardiomyopathy. METHODS AND RESULTS: A total of 113 patients were enrolled in the study and classified into control (n = 25), DCM (n = 38), and DCMi (n = 50) groups. Cardiac functional and inflammatory parameters as well as plasma Nampt and cardiac mRNA and protein Nampt expression were determined at baseline and follow-up after 6 months. Patients with DCM (1.04 ± 0.8 ng/mL; P < .001) and DCMi (1.07 ± 0.7 ng/mL; P < .001) showed significantly increased Nampt plasma concentrations at baseline compared with the control group (0.57 ± 0.5 ng/mL). Patients with higher Nampt concentrations in both heart failure groups showed significant better improvement of cardiac functional parameters (correlation between Nampt plasma levels and the change of left ventricular ejection fraction after 6 months: DCM: r = 0.698, P < .001; DCMi: r = 0.503, P < .001). Moreover, cardiac inflammation did not influence Nampt expression, and Nampt concentrations did not modulate cardiac inflammation in DCMi. A multivariate linear regression model revealed high plasma Nampt expression to contribute to better improvement of cardiac function in patients of both heart failure groups. Moreover, heart failure patients with high plasma Nampt levels showed suppressed cardiac TNF-α and IL-6 mRNA expression after 6 months' follow-up as well as lower B-type natriuretic peptide levels compared with heart failure patients with low Nampt plasma concentrations. CONCLUSIONS: High Nampt expression in patients with nonischemic DCM and DCMi is associated with a favorable outcome and improvement in functional status.


Assuntos
Cardiomiopatia Dilatada/sangue , Citocinas/genética , Regulação da Expressão Gênica , Miocárdio/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Células Precursoras de Linfócitos B/metabolismo , RNA Mensageiro/genética , Função Ventricular Esquerda/fisiologia , Idoso , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Citocinas/biossíntese , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Nicotinamida Fosforribosiltransferase/biossíntese , Reação em Cadeia da Polimerase em Tempo Real
15.
Science ; 345(6203): 1450-1, 2014 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-25237087
16.
Eur J Emerg Med ; 21(2): 105-11, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23751288

RESUMO

OBJECTIVE: The use of emergency medical services increases with the age of patients. Some care providers hold on to the prejudice that these alarms are unnecessary or of a lower importance. We assessed the relation of age and age-dependent emergency characteristics, taking into consideration the ratings of emergency physicians on whether or not emergency cases were considered truly in need of emergency physician attendance. METHODS: Emergency physicians dispatched by the Berlin Fire Department evaluated for each case the necessity of emergency physician attendance. Case characteristics such as the day of the week and location of the emergency as well as patient characteristics such as age, sex, prior status, and care dependency were recorded. In addition, whether or not the physician accompanied the patient to the hospital was recorded as a parameter for emergency severity. Analysis was performed using multiple logistic regression modeling. RESULTS: During the 6-month prospective study period, 2702 cases were evaluated. Emergency medical services are used more frequently by older individuals, especially octogenarians. Emergency cases in older individuals were significantly more often rated as in need of emergency physician attendance; however, the rate of patients accompanied by the emergency physician to the hospital did not differ between the age groups. The age of patients, the primary diagnosis, the day and location of the emergency, and the presence of pre-existing dementia showed a significant impact on the necessity of physician-attended emergency missions. CONCLUSION: Despite common prejudices, emergency cases in elder patients are rated more often as in need of emergency physician attendance compared with those involving younger patients.


Assuntos
Doença Crônica/terapia , Serviços Médicos de Emergência/organização & administração , Serviços de Saúde para Idosos/organização & administração , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Emergências , Serviços Médicos de Emergência/normas , Alemanha , Serviços de Saúde para Idosos/normas , Humanos , Lactente , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade da Assistência à Saúde , Inquéritos e Questionários , Adulto Jovem
17.
J Cardiol ; 63(5): 379-84, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24230464

RESUMO

BACKGROUND: Patients with cardiomyopathy show a significantly increased risk for thromboembolic events due to a hypercoagulable state and platelet dysfunction. The pathophysiologic mechanism underlying the increasing platelet activity in patients with cardiomyopathy remains unclear. We performed a clinical study to elucidate the link between myocardial tissue alterations and platelet activation in patients with cardiomyopathy. METHODS: A total of 30 patients with suspected cardiomyopathy and 10 healthy control patients were included in our study. Hemodynamic parameters were measured by catheterization and echocardiography. Endomyocardial biopsies were taken to determine myocardial inflammation. Flow cytometry was performed to examine the platelet activation by quantification of p-selectin and thrombospondin expression on platelets. RESULTS: The p-selectin (8.46 ± 3.67 AU) and thrombospondin (26.56 ± 23.21 AU) expression was significantly correlated with the amount of CD3+ T cells (p-selectin: r=0.573, p<0.05; thrombospondin: r=0.488, p<0.05) and the endothelial/interstitial activation (p-selectin: r=0.521, p<0.05; thrombospondin: r=0.39, p<0.05). This was found to be independent of hemodynamic parameters, age, and gender. The platelet activation of patients (n=3) with echocardiographically documented ventricular thrombi was significantly increased (p-selectin: 12.57 ± 5.5 AU vs. 8.1 ± 3.2 AU, p<0.05) and this was associated with elevated myocardial inflammation scores. CONCLUSION: Myocardial inflammation is associated with a significant increase in platelet activation and ventricular thrombus formation independently of the hemodynamic conditions.


Assuntos
Miocardite/sangue , Miocardite/complicações , Ativação Plaquetária , Tromboembolia/etiologia , Adulto , Biomarcadores/sangue , Plaquetas/metabolismo , Feminino , Ventrículos do Coração , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Miocardite/fisiopatologia , Miocárdio/patologia , Selectina-P/sangue , Risco , Trombospondinas/sangue
18.
Nat Nanotechnol ; 8(12): 887, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24302020
19.
J Am Coll Cardiol ; 62(19): 1737-45, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-23871888

RESUMO

OBJECTIVES: This study sought to evaluate the role of protease-activated receptor-2 (PAR2) in coxsackievirus B3 (CVB3)-induced myocarditis. BACKGROUND: An infection with CVB3 leads to myocarditis. PAR2 modulates the innate immune response. Toll-like receptor-3 (TLR3) is crucial for the innate immune response by inducing the expression of the antiviral cytokine interferon-beta (IFNß). METHODS: To induce myocarditis, wild-type (wt) and PAR2 knockout (ko) mice were infected with 10(5) plaque-forming units CVB3. Mice underwent hemodynamic measurements with a 1.2-F microconductance catheter. Wt and PAR2ko hearts and cardiac cells were analyzed for viral replication and immune response with plaque assay, quantitative polymerase chain reaction, Western blot, and immunohistochemistry. RESULTS: Compared with wt mice, PAR2ko mice and cardiomyocytes exhibited a reduced viral load and developed no myocarditis after infection with CVB3. Hearts and cardiac fibroblasts from PAR2ko mice expressed higher basal levels of IFNß than wt mice did. Treatment with CVB3 and polyinosinic:polycytidylic acid led to higher IFNß expression in PAR2ko than in wt fibroblasts and reduced virus replication in PAR2ko fibroblasts was abrogated by neutralizing IFNß antibody. Overexpression of PAR2 reduced the basal IFNß expression. Moreover, a direct interaction between PAR2 and Toll-like receptor 3 was observed. PAR2 expression in endomyocardial biopsies of patients with nonischemic cardiomyopathy was positively correlated with myocardial inflammation and negatively with IFNß expression and left ventricular ejection fraction. CONCLUSIONS: PAR2 negatively regulates the innate immune response to CVB3 infection and contributes to myocardial dysfunction. The antagonism of PAR2 is of therapeutic interest to strengthen the antiviral response after an infection with a cardiotropic virus.


Assuntos
Enterovirus Humano B/imunologia , Infecções por Enterovirus/imunologia , Imunidade Inata , Miocardite/imunologia , Miocárdio/enzimologia , Receptor PAR-2/biossíntese , Animais , Anticorpos Antivirais/análise , Biópsia , Western Blotting , Modelos Animais de Doenças , Infecções por Enterovirus/virologia , Regulação da Expressão Gênica , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocardite/metabolismo , Miocardite/virologia , Miocárdio/patologia , RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor PAR-2/genética , Receptor 3 Toll-Like/biossíntese , Receptor 3 Toll-Like/genética
20.
Nat Mater ; 12(7): 652-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23584141

RESUMO

In multilayer white organic light-emitting diodes the electronic processes in the various layers--injection and motion of charges as well as generation, diffusion and radiative decay of excitons--should be concerted such that efficient, stable and colour-balanced electroluminescence can occur. Here we show that it is feasible to carry out Monte Carlo simulations including all of these molecular-scale processes for a hybrid multilayer organic light-emitting diode combining red and green phosphorescent layers with a blue fluorescent layer. The simulated current density and emission profile are shown to agree well with experiment. The experimental emission profile was obtained with nanometre resolution from the measured angle- and polarization-dependent emission spectra. The simulations elucidate the crucial role of exciton transfer from green to red and the efficiency loss due to excitons generated in the interlayer between the green and blue layers. The perpendicular and lateral confinement of the exciton generation to regions of molecular-scale dimensions revealed by this study demonstrate the necessity of molecular-scale instead of conventional continuum simulation.

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